The International Myeloma Foundation Held a Patient and Family Seminar at the Hilton Los Angeles/Universal City from August 16-17, 2024.

- Well, thank you Yelak, I say it all the time, but to be a myeloma doctor and have your boss, a myeloma patient is a very special phenomenon and I'm very, very grateful for Yelak and all that he is doing and has done and will do for the IMF. He did say we have a great team, and I'm blessed by this great team. So, a couple of quick things as we get launched here. How many people here have attended one of our patient family seminars here in LA in the past? So, I would say at least half, maybe slightly over half. So many of you have been to these before. As Yelak intimated, we've made some changes and some structural differences. One, because education is constantly changing. I look at my daughters, I have four teenage daughters and I don't know if their attention span is gone or cause they watch too many TikTok videos and they can watch it for four minutes, but instead of having very, very long lectures, we've shortened some things and we've done things a little bit differently and has already been mentioned, we'd love to have your feedback.

One of the things that we significantly changed for those of you here before, you may remember that we typically started the session today with a Q&A session, often with a local expert, typically Dr. Vescio, who will now join us tomorrow and we will do that Q&A at the end, 'cause we found that questions build up over the course of the day and a half that we're together, so you have the opportunity to do that. By contrast, this afternoon, I'm gonna spend about the next 15 minutes just giving you an overview even, without slides, because I want them to be so hot off the press that sometimes things happen yesterday and I don't have time to prepare slides to give you the hot topics. My disclosure off the start is that I apologize that you're going to have to hear my voice a few too many times today and tomorrow, but only in small bits hopefully.

But hopefully it will encourage you and educate you, as Yelak said, our goals are threefold this weekend. We want to educate, we want to connect, and we want to inspire. If we're not doing those three things, you tell us or you tell us how we can do it better. Educate, connect, and inspire. It's a lot of information to come in, so hopefully there'll be lots of education. My goal and objective is to make the redonkulous-ly complicated things of myeloma understandable and comprehensible, no matter what your level of understanding is here today, that will have high hanging fruit and low hanging fruit, that we will connect you, connect you to the IMF and to all the great resources that we have, but importantly also to connect you with each other, to meet other people going through the same journey that you're going on. And then thirdly, to inspire you, genuinely with the kind of hope that Yelak shared, it's amazing to start a meeting like this with someone who's had myeloma for over 28 years.

I've had the privilege of being a myeloma doctor for nearly that amount of time and I don't say it to be melodramatic, but I don't know if I have seen a more exciting time in myeloma than right now. In fact, as I think about these hot topics that I could cover with you, no exaggeration, one, because doctors, we can ramble on and on forever, but I could come up with 15 easy topics for me to share with you this afternoon, but I've narrowed it down to three. I just want to highlight three things that are hot topics because there is so much going on around the whole of the world, remember the I and IMF is international and so we have the privilege of bringing the greatest minds and scientists and clinicians and patients from around the world to think together about how do we conquer this disease and how do we do it in a way that allows people as Yelak shared with us, to not just focus on not dying, but to live and enjoy the life to their fullest potential. So, lots of different things, I could tell you about the research we're doing in labs, I could tell you about big clinical trials, I could tell you about all sorts of new initiatives that you're going to be hearing a little bit about over the course of the weekend.

Maybe we can go back a slide, there we go. But these three things are the three things that I think are right now particularly hot in the world of myeloma and you're going to hear about them over the next day or so. Number one is more drugs upfront. What do I mean by that? We're gonna be talking for a couple of minutes about how we're seeing more and more combinations of drugs in frontline therapy. For those here tomorrow morning, and I hope you'll all be here tomorrow morning, we will have a breakout session where a group of individuals who are more interested in understanding frontline therapy will go with Dr. Sagar Lonial and he'll share with us a little more detail of what I'm about to share with you in frontline and the rest will stay here and have a relapse session with Dr. Dispenzieri. But when you think about this more drugs upfront, we've now just seen a whole series of clinical trials that have demonstrated the validity of combinations upfront, I'll come back to that. Topic number two, bela is back, if I can use those words, or belantamab mafodotin or BLENREP, you've heard it use different names.

This is a drug that was approved then withdrawn and we do think it's coming back, and I'll explain why. And then hot topic number three, less is more, less is more and I'll explain what that is in just a minute. So let's start with number one. So number one was, more drugs upfront. What do I mean by that? Well, back in the dark ages when I studied myeloma in my training, we used to have one, maybe two drugs for myeloma, that was one of the reasons why, sadly, people didn't live very long, but now people of course are living much longer and thankfully much better with myeloma as a result of all sorts of different drugs that we've developed. And I'm not gonna get necessarily into the specifics of them as much as to understand, the concept that myeloma is a complicated disease. That's why we think of it as multiple myeloma, it's really multiple diseases in one and it's not something that you can just fix with one drug. And what we've come to appreciate is that when we use different drugs together, we have that strength in numbers, but also by different ways of attacking the myeloma. I think of a disease like HIV that had claimed so many lives and still does to a certain extent, but we've really overcome much of the challenge of HIV, not because we found one drug, but because we found the right combination of drugs together. We're trying to do that in myeloma.

So more recently, and you'll hear more about this from Dr. Lonial, here in your session, we've had three, in particular, very large we call phase three trials. If you're not familiar with the phrase, "Phrase three," stick around this afternoon, Yelak and I will explain it to you. But these are are very large trials where two different strategies are compared and in all of these trials, three drug combinations were compared to four drug combinations and the simple result was that four was better than three. And I know that doesn't sound shocking, typically four is better than three. But what was important was we were able to give those four drugs together, because there's always a concern when you come with different ways of attacking the myeloma, that sounds great, but also comes with different side effects and so using these in the right combination. So we had a clinical trial called the Perseus Clinical Trial, which compared the standard regimen we've historically used VRD or Velcade, Revlimid, Dexamethasone, and it added Daratumumab to it or Darzalex to it and we saw a very significant benefit of adding the Darzalex to the VRD and that's really become the new standard of care now in patients who are eligible for transplant.

But what was remarkable is we saw the same thing even in those patients typically not going to transplant. So we've had now a very similar clinical trial, adding this time, isatuximab or SARCLISA, which is another kind of monoclonal antibody, we'll explain what those are later, similar to Darzalex, isatuximab being added to VRD versus VRD alone. And we saw similarly in that trial a benefit even in those patients who are typically older and not eligible to go to transplant and there was yet a third trial called the Benefit Trial, which also used isatuximab VRD and this time compared it to just isatuximab with RD or with Revlimid and Dexamethasone. And in all of these cases, four was better than three and although of course when we take more drugs, it comes with potentially more side effects, we're getting much better at managing them and reducing the toxicities as we call them, and I'll explain a little bit more. So for those of you who may be early on in your journey, you're likely gonna see a greater combination upfront and the hope is that if we give more upfront, then we can actually give less over time. I'll come back to the less is more concept in a minute, but it's not like it's four forever, the idea is let's squish this disease down to almost nothing and then patients can go on to lesser therapy.

And ultimately as some of us were chatting at the break on my favorite therapy, nada, nothing. I love giving my patients nothing. It's a great prescription to fill, every insurance company approves it, everybody's 100% adherent to it, everybody loves getting nada. Alright, so that was hot topic number one. Hot topic number two, bela is back, belantamab mafodotin or BLENREP was a drug, the first of its kind in myeloma, called an antibody drug conjugate. What does that mean? Again, Teresa and I are going to do a quick myeloma 101 later where we have a little back and forth describing the mechanisms of drugs. But in simple terms, this is a drug that hooks onto the myeloma cell based on something that's sticking out of the myeloma cell called BCMA or B cell maturation antigen and I think of it this way, it has a backpack with it and this backpack has got a toxin in it or something that's very toxic to the myeloma cell and it can drop that backpack into the cell. The drug was approved a number of years ago and typically, again, I'm not going to give you a whole lesson on how drugs get approved in this country, but it gets approved by what we call accelerated approval, meaning if it can prove that it has some benefit typically on its own, then the drug gets approved until a larger clinical trial is done, where it is compared.

Well the comparing trial that was done did not turn out to be positive, meaning it didn't show a benefit over the standard of care, so the drug was withdrawn, but two other clinical trials were already in development, large phase three trials, the dream trials as we call them, dream seven and dream eight and those just read out over the last couple of months. And in each of those situations we saw that belantamab had a significant benefit. Dr. Dispenzieri will talk about this more in detail tomorrow, but I'm just giving you the appetizer. I'm the appetizer, they're the main dish, so I'm just giving you the little preview to it. But this drug is very important we believe because it is quite easily administered, it's just given IV in the clinic, it doesn't require the collection of T-cells, it doesn't have a lot of challenge in giving it. It does have some side effects in particular the way it can affect people's eyes, but again, we've learned a lot about this and how to dose it and how to reduce those kinds of side effects. So it's not quite ready to return to the clinic in prime time, it's going through the usual regulatory process through the FDA and so on. But I think we all believe that belantamab will be back and it's good because we want choice for our patients.

And then lastly, less is more, what do I mean by that? If you look at almost any drug we have in myeloma, it has gone through an evolution from when it was first approved. And again, I'm not gonna go through a lot of detail of how we approve drugs, but drugs are typically approved through a process, I do a lot of what are called phase one trials where we test a drug to see what is the right dose of this drug. And the general premise is, the more I give, the better the patient's gonna respond. So a phase one trial typically starts with really a tiny dose, like just smell the bottle, barely get any of the drug. But then as we build up to the dose, we build up to what's called a maximum tolerated dose, or MTD, where we feel that there aren't so many side effects that would prevent us from being able to give this drug, but we give it on the premise that more drug is better and typically with older style chemotherapy, the bald and barf kind of chemo, that's generally true, the more you give, the more cancer cells you can destroy, the better it's gonna be. But if you look at the history of myeloma, almost every drug that's gotten approved over time as we've gotten to use it, we've actually reduced how much we give.

We've gone from giving Velcade twice weekly to once weekly or carfilzomib from twice weekly to once weekly, selinexor from twice weekly to once weekly. We've gone from giving certain drugs IV to giving them subcutaneously.

- At this point, I'm gonna turn it over to my partner in crime, Teresa Miceli. Hopefully you all know Teresa. One of the great things we did at the IMF was to recruit her to work with us, as she also continues to work at Mayo Clinic in Rochester. So we were Mayo buddies at one point when I used to work at Mayo Clinic in Arizona. And she's gonna talk to us a little bit about shared decision-making. So TM, I'll turn it to you, boss. - Thank you. I don't want anyone to think that I'm stalking him, but it is a pleasure to work with him in this capacity, as well as at Mayo Clinic. So for those of you who don't know me, I a Teresa Miceli. I'm a registered nurse. I had the opportunity to work in the myeloma space since 1991. Yes, I was about three years old when I started. And so at that time, I was working in stem cell transplant. I was recruited or invited to be part of the Nurse Leadership Board with the International Myeloma Foundation, which was started in 2006. And you'll hear from one of my colleagues tomorrow, Tiffany Richards, on symptom management, and we do a lot of work with educating patients and other health care providers. Because as many of you know, myeloma's not that common of a diagnosis, and we'll go over that later today with Dr. Joe and myself during our myeloma 101 conversation. But I did, with open arms, join the IMF as an advisor to their InfoLine.

So if you call in, you'll hear from Paul, Missy, or myself. And if you have questions, please, let us know. We're happy to take your questions. And if we don't have the answer, we're gonna find the answer, or we'll make one up, but that's not usually the case. My work in myeloma has, if nothing else, told me how important it is that patients and care partners be a part of the decision-making that goes on with them, for them, when it's related to their treatment. And that's the topic that's near and dear to my heart and we'll be talking about right now. I wanna really go over what shared decision-making is, what are some of the influencing factors, and as Yelak says, I want to empower you, provide some strategies for how you can be a better part, a greater part of decision-making when it comes to your health care. You will be hearing a lot today and tomorrow, as Dr. Joe said, about the treatment schema, the treatment landscape, and how we approach myeloma care. What's always important for us to remember is that we are treating a person with myeloma, a family with myeloma, that has commitments to other parts of their life, not just myeloma. That you have family, that you have jobs, social responsibilities. Yes, we wanna manage the myeloma and make sure the symptoms are cared for, but you as an individual need to be taken into consideration and that's only gonna happen if you're part of that decision-making team. So what is shared decision-making? This is not a new term. This is a term that's actually been around since the 1970s. It's really all about understanding that there's a decision that needs to be made, and patients understanding the risks and the benefits or the pros and the cons of what happens with those treatment options and the decisions that are made. And making sure that your goals, your preferences are included with all of that decision-making. There are steps in this process, and I like to use a similar analogy to going out to dinner. That may seem simple, but yet, when we break it down into the simplest terms, making a decision is first part of, you know, knowing a decision needs to be made. So I get to LA yesterday, and you might've noticed, I'm from Minnesota. Yep, you can hear it, right?

I get to LA and I wanna go out to dinner. A couple of options, right? Well, before I got here, I started Googling what might be a good option for going to dinner. But I needed to rely on my LA colleagues to help me decide. And they're like, "Oh, we could go to Chinese, we could go have, you know, Indian food." I'm like, "You know what, I hate curry." I know that's wrong for me to say, but I do. And so they started offering some options, and I eliminated some of those based on what my preferences were. I'm like, "Oh, I don't wanna go to the burger joint. I don't need any more fatty foods." Well, you might notice that just down the street or a few blocks away, probably 200 feet, and it took about 20 minutes. That's about right in LA, yeah. There's a little place called Miceli's Italiano Restaurante. Okay, so we had to go there because that's my last name. I figured I might know somebody that was there. I didn't, but it was still fun. It was a good experience. But even in that decision-making, needed to have the information being brought in. We needed to make a decision, needed to understand what my options were and what my preferences were when it came to making that final decision. We did end up going there. We had a good experience. Kinda reviewing it all, it's like, well, maybe I wouldn't go back just for the food. It wasn't that great. Don't tell them I said that. But that's all part of that shared decision-making. And myeloma's a much more complex topic than that, but when you break it down into the basics, it's kinda the same thing.

You know, does a decision need to be made? Are we at a point where we need to make a decision, a choice in treatment, a change in treatment? You're leaning on your health care team so that you understand what those options are, what the risks, the benefits, the pros, the cons are, but your health care team needs to know how it's going to impact you, what your preferences are. Coming together to come to a decision that best fits not only what we need to do with myeloma, but your preferences, and then continuing to evaluate how things are going, follow-up visits, deciding is this still the right track. There are advantages that go with this. As you can tell, I'm very passionate about this, but really key to this is that it requires you as a participant to stay informed. And so I applaud all of you for being here, being a part of this education session, and continuing this education journey while you're continuing the myeloma journey. It helps to alleviate some of the fear that goes with that uncertainty if you don't really understand what is happening. The decisions being made are more likely to reflect your own personal preferences if you are a part of it, if you are truly having this conversation. And overall, it does impact quality of life. If you are part of the decision-making, if your preferences are being involved, this is undoubtedly going to impact your quality of life. Dr. Terpos, who is a member of the International Myeloma Working Group, I think he states this really well is that efficacy to each person means something different. What's important to me is not necessarily important to you. Right?

And so taking each individual's considerations, preferences into thought really does constitute the best treatment choice. So there's some things that also influence our ability to make the choices that we want. In an ideal world, well, in an ideal world, we wouldn't have myeloma, but we do. And so what influences whether we can make the most optimal choice for us? Sometimes it's the diagnosis itself. For those of you who were sort of urgently diagnosed, maybe you went to the emergency room or were admitted to the hospital, there was sort of this urgent need to get treatment started. We didn't have a lotta time to linger and think about it. However, for some people who maybe are transitioning from a smoldering state into an active state that requires treatment, there can be a little bit more time to gather that information, really think about the choices and the options that are available. And that's also true when it comes to a relapse process. Some people have what we call biochemical versus a very fulminant relapse, and we'll go over that a little bit more in a couple hours. There's also, even in our country, the challenge of: Do we have access? Whether it be financial issues related to having access to drugs, or maybe, you know, somebody would say, "I would want CAR T first thing, right away." I did say CAR T right away in my talk, okay. But it's not available until second or third line and that was only a few weeks ago that that was approved. You couldn't get it until after four lines of therapy. That's true with our biospecific therapies. So sometimes it's about access to the actual therapies that we want. This is a very complex diagnosis, and as a patient, you do need to stay up to speed on what's going on so that you can be a part of that decision-making. Maybe you don't feel good, especially when you're first diagnosed or you're relapsing, and you just don't have the mental and physical energy to really be as much a part of that conversation as you would like to be.

There is still that sort of patriarchal health care doctor-patient relationship that goes on, where patients don't always wanna question what their doctor is telling them or saying. I was speaking with somebody on the InfoLine who was like, "You know what, I really don't wanna go to this particular drug because I know about the side effects, but that's the one my doctor is encouraging me and kinda pushing me to go with." And I really, I commended her for saying, you know, providing her rationale and giving the understanding based on her preferences why that was not the best option for her. When it comes to our providers, they would like to spend as much time as they possibly could going on about everything myeloma they can. But believe it or not, there is somebody that they're gonna be seeing right after you. And even though you've already waited 20 minutes, that person's gonna wait 30 minutes. And so there are time limitations to being able to have this very robust, detailed conversation. And we'll talk a little bit about, you know, being prepared for a medical visit. And sometimes that also means sending your portal questions ahead of your visit so that they are, one, on record, and sometimes you forget when you get there, or maybe the most prioritized questions need to be sent for some consideration. So there are a variety of things that can influence whether that treatment decision process really goes in the best of flow as we would like. So some strategies for this concept of empowering you and helping you to be a better part of patient treatment decision-making is, like I said, staying informed. And you'll see outside that there are a variety of publications available that you can take this weekend, but you can also get more of them at myeloma.org. You can order them online. We can have them mailed to you. They're all free of charge. I encourage you to take what you need for now, as well as what you might be thinking of for the next step in your treatment process.

There are a variety of webinars that have been recorded, and they're available on myeloma.org. And of course, the InfoLine, I will continue to plug the InfoLine. The other part of this is not just gathering knowledge, but really doing some soul searching. What are your preferences? What are your priorities in life? I was working with a gentleman who is a guitar player. And he was very, very concerned about receiving bortezomib, which is known for causing neuropathy. And so we really had a very long conversation about that treatment approach, how this was considered to be part of standard of care for frontline therapy. We could give it a try and see how it was doing, and if there were any side effects he was experiencing, and then we could make a change in his plan. And so again, those personal preferences, that diving deep into what you are thinking is a priority. Maybe you're ready to go to a stem cell transplant, but you have a wedding next month that you really wanna look like you in those photos. Daughter's getting married, whatever it might be. Talk to your health care team about the timing of those sorta things. Be a part of the conversation. Ask the questions. Maybe discuss it ahead of time with you and your care partners so that you can really refine what those questions are. Come to a treatment decision, again, together based on what your preferences are. We can always adjust it. We can review, see how things are going, and make a change if needed. It's all about coming together with a treatment decision that works best for you and against your myeloma.

So if I were to ask you: Who is is your health care team? Well, I think it might be pretty easy to start out and say, "Well, I've got my primary care doctor. They're the ones who sort of were concerned about this being myeloma and helped me get diagnosed. I went and met with a general hematologist, and he got me started on treatment but really strongly recommended that I see a myeloma specialist," like Dr. Joe. And you know, so these are some key components or key members of your health care team. If we add to that, we have maybe your kidney doctor or your bone doctor or your endocrinologist who's managing your diabetes now that you're on dex. You have your nursing staff, your nurse practitioners, allied health, pharmacists. You've got your social network, your spiritual network, all of these people that are part of your health care team. Who haven't we identified yet in this health care team? - The patient. - The patient, absolutely, central to all of this. You become the hub to all the spokes that makes this wheel move forward. And it's important to understand what the roles are for all of these individuals in your health care team. And the reason is is, you don't wanna go to your primary care doctor and say, "You know what, I think it's time for a new myeloma therapy. What do you recommend?" That's not gonna fly very well. Just as you don't want to be going to your hematologist and saying, "So what do you wanna do about my blood pressure?" You really wanna kinda balance that out so that you are using, optimizing your time with each provider in the way that is going to be best on your overall health care plan. Make sure that you're seeing primary care to do all those health care screenings, those survivorship tests. Make sure that you're seeing your subspecialists for specialty needs. And keep a contact list of all these people. And I also recommend that you do a little journaling of, you know, what treatments have you had. When did you get 'em? What were you feeling like when you were on those therapies? In the event that the discussion comes up somewhere else that you need to know, "Ooh, that's right, that medication really made me feel pretty lousy. I'm not sure that I wanna do that again." Be prepared for your health care visits when you're going to see your doctor.

Get your medications in order ahead of time. Write down those questions, send 'em through the portal. If you have paperwork that needs to be completed for you or a family member, make sure you have those prepared and bring 'em to the visit. When you're there, provide them with the updates, good, bad, and ugly, whatever it may be. What's going on with you, your myeloma, your family. It's not just about your myeloma. It's about all that's going on with you. Are you having symptoms? Have they changed? Better or worse? What's made them better or worse? Making sure that you're prioritizing your questions and effectively communicating with your team to get that information in during your visit. Making sure that you're also knowing what the follow-up plan is when you are done with your visit. Are you coming back in three months, one month? Are you having blood work? Are we gonna be doing a bone marrow biopsy? And making sure that you have a care provider with you or, excuse me, a care partner so that at those pivotal visits, when you may be making some decisions or changes in your plan. Think about if there is a telehealth option or telemed option. You wanna prepare in the same way, but you also wanna think about your surroundings during that visit as far as, you know, are you gonna have to show a body part? You wanna be in a discreet place to do that or wear clothing that you can show a rash or a new mole or something that might be coming up. You don't wanna be in a car or in a public place for those visits. Know if you need to have blood work drawn ahead of time before that actual video visit so that the doctors have something with lab results to look at. And as I mentioned, care partners are really important, and it's not just a care partner, but developing a care network. And what I mean by that is, you may have your spouse or significant other sitting by your side and available to you on, you know, a regular basis. There's some people who don't. They live alone. That Solo and Strong support group would be a good option for them.

But we need to think about more hands make lighter work, okay? And so having a care network allows for people to use their skills, their strengths to help you out. It doesn't even have to be somebody who's here in-person. It could be somebody who's helping from a distance, even hired help, like ordering groceries and having them delivered, a service to mow your lawn if you're not able to push the mower or ride the mower. So thinking about the variety of options available to expand your care network, because we do know that myeloma really does carry the largest burden of symptoms of really any diagnosis when it comes to blood cancer disorders. So as you go through the next couple of days, and I really wanna set up that we are wanting you to be thinking about: What are the changes that you may be needing to decide on? What decisions are coming your way as far as your treatment goes? What are the options? What are your preferences? That really does take a little bit of soul searching. Think about what's important to you. Create questions that will lead to better understanding. "What more do I need to know? What am I not asking that I should be asking?" And become truly an active member of your team and the decision-making process.

- Okay, so I'm going to be talking about advanced care planning and I really want to thank the IMF for inviting me to come and talk to everyone about this. I'm very passionate about feeling this is an important subject for all of us. Little information about me. I've been a nurse for about 27 years. I spent 14 years in bone marrow transplant, which is where I really got interested in multiple myeloma. And I helped lead a support group in the Kansas City area for multiple myeloma patients. So, the question is, what is advanced care planning? People often really don't understand this term. It's really just discussing and deciding what sort of care you would want if you became unable to speak for yourself and being certain that the people who would make decisions for you are both identified and know what your wishes are and would also be able to carry out those wishes for you. Keep in mind that this is something that goes into effect only if you become unable to speak for yourself. And people often think that that's something, well that's never going to happen to me. But it's really not uncommon, especially a myeloma patient may have often been too ill to really be cognizant or maybe you've had surgery and during that time you certainly weren't able to speak for yourself. If you've had a colonoscopy, you've had time period there that you were unable to speak for yourself. And in a lot of those situations, it's unlikely that something emergent is going to happen.

But it can. It's important that someone's identified as your spokesperson and that that person knows your wishes. So do you have an advanced directive? Lots of times people have completed a will and when they've completed the will, they may have completed a healthcare and financial durable power of attorney. They may have also completed a living will. A living will is a great way to identify what your wishes would be. So for a lot of people, this is kind of a place where they'll start thinking about what sort of care I would and would not want. But for a lot of us, we really don't fully understand what the options are. And medical care becomes more complex every day so that the options that were available five years ago, there's an entirely new set of options. So it's important to kind of know what's available and what would I want. This is an example of a healthcare power of attorney. They vary from state to state, and I have with me today out in the lobby area, some copies of the California healthcare durable power of attorney. This is the document you use to identify the person who would be your spokesperson. Now one of the things that is important to keep in mind is that this person is able to carry out your wishes. Sometimes if we're talking about somebody that we're extremely close to like a spouse, sometimes it's hard to carry out the decisions that that person may want because as their spouse, you want to do everything to hold on to them. Or perhaps you have a marriage like I have where I'm the decision maker in our household. I'm pretty sure that if I became unable to speak for myself, my husband would wait for me to wake up to make a decision. That's just who he is. So as a result, my husband's not my spokesperson.

I have a good friend who is my listed spokesperson. A little more information about understanding what your wishes would be. One of the things that comes up is code status. Now, a lot of you, if you've been in the hospital, they've probably asked you what's your code status? And you think, what does that really mean? Your code status means if I were to pass away, if I died, would I want to be resuscitated? And people are often kind of shocked by this idea that CPR has to do with having died. But the reality is, is that CPR is not something that's performed on the living. It is only performed if you are not breathing and you do not have a heartbeat. This right there tells us the reason that these decisions need to be made in advance. If you're not breathing and you don't have a heartbeat, you can't say whether or not you want this type of treatment. You can't say, "Yes I want CPR." Or, "No, I don't." That's the reason that CPR is one of the few medical treatments that by default is done, it is performed. So if you don't wanna have CPR performed, it's very important that you have that identified and that your loved ones know what your wishes are. One of the frustrations I hear from patients is every time I go into the hospital they ask me this question, I have to have this conversation over and over. That's because when you're in the hospital, that code status only is alive while you're in the hospital. When you're discharged, it expires. It's not transportable from the inpatient setting to the outpatient setting. And there are starting to become documents available that are transportable.

And in a moment, I'll talk a little bit more about those. The other question in healthcare is how aggressive you want to be, because there's this question about a do not resuscitate. But the reality is, is that there is lots and lots of healthcare that happens long before a person codes, before a person goes into cardiopulmonary collapse. There's all kinds of meds, therapies, perhaps you're gonna be put on a ventilator, go into ICU. It's important that you know what these options are and whether or not those are things that you would want to take place. So we'll talk a little bit more about CPR. Again, I mentioned the fact that CPR has only happened if you're not breathing, you don't have a pulse. If there's anyone in here that's done CPR training, you've had to do that thing where you run up and you say to the mannequin, "Annie, Annie, are you okay?" If Annie responds we don't give her CPR. If you don't want to have CPR though, if Annie didn't wanna have CPR, she better have completed a do not resuscitate order ahead of time. And this is an order that needs to be done with a physician. It needs to be done with a physician for two reasons. One is, is that it's a physician's order. So it definitely requires a visit with your physician, a discussion with your physician, and that physician's signature. The other reason that it requires a physician involvement is that it's an important question. And your doctor is the person who's going to be able to provide you with the important information to give you the perspective and help you understand what's the right decision for you. The one thing that I try to make people aware of is this is a very personal decision. It's not that you should do what anyone else thinks you should do. You should be making a certain choice. This should be the choice that is correct for you. You are allowed the choice of making a natural, allowing a natural death, which is what happens if someone does not have CPR? You are also welcome and able to choose to have the most aggressive of care.

It's what's right for you. It's what's right for your loved ones and it's important to have that conversation. So a little bit more about what all the levels are of medical care before CPR, and there's a lot of great detail here. One of the forms that I have with me today is that out of hospital do not resuscitate order. And it has all the more specific details here about full treatment, mid label treatment, best supportive care. And one of the things that is really important for people to understand is that a person can choose to not have resuscitation, choose a DNR order, and yet still want the most aggressive of care. And by that I mean is as long as you are alive, breathing and have a pulse rate, you can choose to go to the IICU, be on a ventilator, have all the most aggressive therapy. I find that people are often very concerned that if they choose to be a do not resuscitate that then they're just gonna be left in a corner and not get any care. And that's not at all true. And in today's medical world, we give tons of treatment keeping people from progressing into a cardiopulmonary collapse. I mentioned earlier about the fact that that do not resuscitate order expires each time you get discharged from the hospital. And for a long time, all there was was a simple do not resuscitate order. It only addressed whether or not you wanted to have CPR. It was called an out of hospital do not resuscitate order. Now, there are starting to be more technical options.

Again, because there's just so many more options in healthcare. It does again, require a conversation with a physician and a physician signature. Most states are now developing different types of transportable forms in the state of California. It is a polst, which is a physician order for life sustaining treatment. And I have an example of the form out there if you're interested in seeing a copy of it. If you're interested, I encourage you to pick one up and then plan a time to talk to your doctor a little bit more in depth about this. It provides more control over all the various options for people who have a serious illness, are at a higher risk of developing complications. So once you've completed all these forms, people are often confused about what they should do with it. We have this tendency to think this is an important form, I should file it away someplace. They wanna put it in their safety deposit box. They wanna put it in their filing cabinet. But the thing is, is that in case of an emergency, what you need is to be able to get your hands on that document quickly. People who work as emergency care providers, EMS, that type of thing, they've been taught to look a couple of places for documents and medications, bedside table and the refrigerator. So we lots of times encourage people to put these documents in an envelope and stick it up on your refrigerator. Then if you're found down, your loved ones are able to go, "Wait, Mary has a form on the refrigerator to address her wants in this situation." The other thing that happens these days is that life is just more complicated in the computer age. And not only is life more complicated, but death is more complicated. Most of us have all kinds of things on our cell phones, we have photos, we have all these online accounts. We probably pay bills that way. If you're too ill to be able to make your medical decisions, you're also too ill to be able to pay this month's electric bill.

So, it's very important that someone knows how to access your phone and that there is someone you trust that you share your codes with, the passwords to all of your accounts. All of this is good information for you to have. The most important part of all of this though is conversation. What matters the most is the conversation that you have with your loved ones, with your friends, with your physicians and other healthcare providers. It's important that you're able to talk through what's important to you and that they understand. It's comforting for your loved ones to be able to say, "I know what Bill wanted in this situation." It might still be really hard for them, but they're confident that they are carrying out your wishes. So what really matters is for you to have this conversation. And I know it can feel really awkward, but I encourage you to just kind of find a time. Interestingly enough, there's a big push for this to be Thanksgiving conversation.

The family gets together, and they talk about these things. Fortunately, there are a lot of great online resources to kind of help. I recommend prepare your care for your care.org. It has options for multiple states. You can choose the documents correct for your particular state and it also helps you work through all of these questions. You can work with your loved ones and go through these things and you end up with some completed documents on both what would be your preferences and identifying your healthcare providers, your healthcare decision maker. Another big thing nationally is April 16th is National Healthcare Decision Day. You can usually find a lot of options online. This particular project is the Conversation Project, has National Healthcare Decision Day. Out at my table today, I have some cards called Go Wish cards. And I welcome you, come out and pull a card. What you do is you look at that card and you think, is this something that would be important to me if I were at the end of my life? And it's again, like that thing that we mentioned that Teresa mentioned earlier, we have this tendency to think that everyone feels the same, but they don't. So you need to kind of look through things, decide is this important to me? And just get conversation started. Also, if your cancer center has a social worker, they are a great resource for this type of information, for helping encourage these conversations, helping you complete your healthcare durable power of attorney. So, I just ask all of you to recognize that the time to plan is now, nothing about this is actually scary.

Planning is something that is very adult. It's something that we normally do all the time. We plan for funerals, we plan for weddings, we plan for a baby, we plan for education. Planning for our healthcare is something that we should all do as well. And I just encourage you to get educated and recognize this isn't as scary a topic as you might think. Thank you.

- This is gonna be a really great session. And I say that maybe a little biased because Dr. Joe, and I worked on this together. But as I mentioned, I've been in the myeloma space since 1991, and over the years I've had the opportunity to hear a wide range of questions, and questions that are really important to the myeloma experience coming from patients, which is why I've developed a new nurse navigator role at Mayo Clinic to help people understand their diagnosis, expectations of the medical visits, the referral to Mayo Clinic, things of that nature. And so today what we're gonna do is have a sort of a little back and forth conversation, Dr. Joe and I. We're gonna be talking about, you know, some of the questions, frequently asked questions, that come up on this myeloma journey. You've met both of us, so I won't go through all of that list of stuff and junk. You know who you are.

- I hope so.

- Yeah.

- Maybe not by tomorrow night, but yeah, I'm still good.

- But one of the first questions that comes up with patients is they will say, "I've never heard of this diagnosis before." How common is this?"

- So it's a valid question, and you know, whether you've had myeloma for a long time or not, one of the things we hope to get out of this session is to equip you to be able to answer other people's questions, so it's not just so you know the answer, but being able to frame it for someone else. So when we think of myeloma, it's not a very common cancer. It accounts for about 1 to 2% of all cancers. We see about 36,000 new cases here in the US this year. Tragically about 13,000 people will die from myeloma in this year, which makes us so passionate to work towards that. Although the numbers do change, thankfully over time. And we do know that there are certain things that put you at greater risk of myeloma that I know we're gonna talk a little bit about in a moment. But we do see differences by race and gender. So I'm gonna give a talk tomorrow on health disparities in myeloma and specifically what we at the IMF have done, and are doing to try and help reduce that disparity. 'Cause if you're, like myself, of African descent, you're gonna have twice the risk, unfortunately, of developing myeloma. But also we know that myeloma is more common in men than women. And then lastly that the average age, and of course average is a weird thing 'cause it's a huge spectrum, but the average age of myeloma is about 69. We're gonna see, as I described tomorrow, that it's considerably younger in patients of Latino American background, or African American background, but the average is about 69.

- Well, and then of course comes the next question, you know, not only how common is it, but how did I get this? What causes myeloma?

- Yeah, so for the vast majority of patients, we really do not know, right? You did not earn myeloma, sadly, in that respect, in the sense that there isn't something that we know caused it. We're gonna be hearing a little bit over the course of this weekend, some of the research and work we're doing this incredible program in Iceland, you know, where we've screened 90,000 individuals, and we're trying to match and understand is there something in our inherent genetics that puts it at risk of it? But for the overwhelming majority of patients with myeloma, we don't have a reason or a cause that we know can connect them to their myeloma. In a small fraction of patients, we know that there are certain things. So some of our veterans that have been exposed to Agent Orange. Firefighters that have been exposed to multiple fires. We did actually as the IMF, we looked into the incidence of myeloma in first responders after 9-11, for example, and there was a slight increased risk. But then of course there are other things that we can't control, like our family history, our race, and ethnicity as I've already commented on. And so again, we still don't fully understand it. When someone gets diagnosed with myeloma, we don't say, "Okay gotta test all of your family members like we do with certain cancers." But we do, we sometimes are in situations where there are multiple family members that have been diagnosed with myeloma. We don't understand the genetic pattern of that yet. We're studying it and trying to understand it. But there may be some situations in which we'll say, "Maybe we should test." You know, I was in clinic not long ago where someone came in and two of their siblings had myeloma, and they had myeloma. So you have three siblings with myeloma. There were five total. The other two wanted to get tested. And I think that's very appropriate, but that's obviously a very unusual situation. But as you've listed here in the slide, Teresa, in most cases we just don't really know what causes myeloma.

- We know that it arises from the bone marrow. The bone marrow is a very important component of our body. Can you help us better understand what the bone marrow does, and explain it to me like I'm a 21-year-old?

- Yeah, at least you said 21, which means you're legal drinking age. So some of you have heard me use this analogy before. People use different analogies in different places. I was teasing Dr. Gertz at our last patient family seminar in Minneapolis that he always talks about the garden. And I'm like, "Well, he's got a garden, I've got a vineyard." So let me talk about the vineyard analogy. So when you think of what goes on in your blood, so your blood is circulating through you right now. That is the coolest having the dog right there. I love that by the way. I just gotta say, I was like he's just taking it all in. And I love it. Or she. So when you think of your blood is circulating right now, it's made of two bits. There's the liquid part, and there's the solid part that's inside it. The liquid part we call the plasma, and that's kind of what carries things. And there's some proteins and so on in it, but it's mostly liquid. And then the solid stuff are what we call your cells. These are the circulating cells. And you have three kinds of cells that circulate in your blood. And I like to think of them as the picture is here of wine. So you have red, you have white, and you have rosé. Okay? So you have red cells, you have white cells, and you have rosé cells, or as we call them, platelets. So very simply, red cells are just little red trucks that carry oxygen. That's all they do. You breathe in into your lungs, and all that air comes into your lungs. These little red cells, they come, they pick it up like a truck, pick up that oxygen, go deliver them to the tissues, your brain, your, the rest of your body that needs it, drops it off, comes back for more. That's all red cells do. As I always say, I've offended every hematologist in the world right now, and that's okay. But I mean it is the most important organ, obviously, right? The blood. Okay. This means "yes," all right. So you agree with me, right? Like the heart, it's just a pump, useless without blood. The kidney, a filter, useless without blood, right? So blood really the life of the fleshes, and the blood, right? I'm even quoting scripture now. All right, so point being is you've got these red cells that carry oxygen. White cells, which we'll talk a lot about this weekend, are your soldier cells, as it were. They are what protects you, your immune system. Interestingly, we have five kinds of white cells. Much like we have five major branches of the military. And these cells protect you, and they circulate in the blood to go and defend. So if I get stung by a bee, or I don't wanna get too personal with some of our crowd here, but if I get stung by a scorpion at an IMF meeting. Where's Mike? And those white cells will rush to that area, and try and block off and protect you. The rosé cells, or the platelets, are little cells that help you clot. So if I were to cut myself, the first thing that gets there are the platelets. I think of them as like the ambulance cells. They get there first, they plug up the hole as it were. And then they make a phone call to what are called factors, which form a strong blood clot. When people have hemophilia, for example, they have issues with their factors not being able to form a strong blood clot. So these three cells, the white, the red, the white, and the rosé are what circulate in your blood. And they're all made in the factory of your blood, right? So if I wanna know how good a factory is working, like a car factory. If there was a car factory down the street, we would say, "Okay, let's see how good the car factory is working." I could look at just the cars that have come off the assembly line. That tells me quite a bit about what's going on in the factory. But if I really want to understand the factory, the metal, the rubber, the working conditions, I need to go inside. And the bone marrow is the factory of our blood. And we go into the bone marrow, we see all this machinery that makes the white, red, and the rosé. That makes all these things that come out of it. And in particular, there's one small little area of the factory called the plasma cell. It's a very small part of it. Normally 1 to 2% of the whole factory. I don't know if it was like a big car factory, it might be the section that makes steering wheels, right? Really small, very important, but very small. And these are called plasma cells. And I'll stop here in a second, Teresa. But these plasma cells, as you've all come to learn, are so important to life because the plasma cells are charged with making the proteins or the antibodies that fight off infection, right? You know, we love to use words that patients don't understand in medicine, right? That's how we do it, right? That's that's what they teach us for like 20 years in med school, right?

- And when patients start to catch on, then we do it in an alphabet, an acronym,

- Exactly, exactly.

- just so it's even more confusing.

- And so we don't call them proteins, or necessarily antibodies, we call them immunoglobulins. Which just means immune proteins. And so these immunoglobulins are these proteins, are the things that help you fight off infections. Myeloma is a cancer of the plasma cell. And again, what is cancer in its essence? I always say three words, identical, uncontrolled growth. Identical, uncontrolled growth. It's easier to conceive of a piece of lung tissue, or breast tissue, or colon tissue but it's the same principle. So these plasma cells now start growing, instead of making good antibodies, good immunoglobulins that fight off infection, they make bad antibodies, or bad immunoglobulins that can start to attack you.

- But if we have a whole bunch of these plasma cells, these immunoglobulins, these antibodies, shouldn't that be good for us, and be able to protect us from infection?

- You think it would. But these are different plasma cells. They're plasma cells that have gone off the rails a bit. They're a little bit gone rogue. And that's what cancer does, right? So breast tissue that is cancerous is not normal breast tissue. Lung cancer that is, lung tissue that becomes cancerous is not good lung tissue. So same with these plasma cells. So when we have normally functioning plasma cells, we say they make what we call polyclonal antibodies, which means, "poly" means many or several, different shapes and sizes that can fight off COVID, and tetanus, and measles, mumps, rubella, all the things that we get vaccinated for, and that we've been exposed to, in myeloma, they now become monoclonal. What was our definition of cancer? Identical, uncontrolled growth. So it's the identical piece that becomes important here. And so now these plasma cells are producing these little Dr. Evil's Mini-Mes, right? Of all the identical little cells that now produce these antibodies that can damage the body.

- Okay, so if I have one of these clones, these monoclonal proteins in my body, in my blood somewhere, do I have myeloma?

- Now that's a great question, Teresa, if only I had a slide that can demonstrate that there are actually three phases. So again, not trying to make light of it. So remember earlier we said myeloma is relatively rare cancer, 1 to 2% of all cancers. On the other hand, the precursor to myeloma is incredibly common. In fact, having a little amount, a little schmutz of these abnormal cells is incredibly common. 5% of people over the age of 40, if I go test them today, I can find a small amount of this monoclonal protein. 5% of people over the age of 40 don't have myeloma. So we've had to make this distinction between do you have just this tiny little bit of it? Almost like someone may have a very small mole, it's not skin cancer. It has the potential to become skin cancer, but it's not. We don't call every one of those benign moles, melanoma or skin cancer. We can't call everyone that's got this little abnormal protein, truly myeloma. So we have these three categories, and our big study in Iceland actually has been helping us understand this even better. And the three categories as you see them here is something called MGUS, or monoclonal gammopathy of undetermined significance. That was coined by our-

- He's channeling Robert Kyle .

- Yeah, Dr. Bob Kyle, one of the grandfathers of myeloma. And basically this term is designed to say, "If we test your blood, and we find this little bit of protein, but it's not at a high level, and it's not damaging the body in any way, you have MGUS." At the other extreme, if people have this bad protein, and it's causing damage, the classic CRAB criteria that we'll come to in a moment, then you have myeloma. And then there's this area in between where people have more than the little schmutz, but not enough to have true myeloma. That little intermediate area is what we call smoldering multiple myeloma. As you can see, we define it by, if we do a bone marrow, how many plasma cells there are in the bone. Remember normal was only 1 to 2%. And we look for other features, but there is a risk of going from MGUS to smoldering, and from smoldering to active myeloma. The majority of people with MGUS in their whole lives will not develop myeloma. The vast majority do not. But there is a subset that do, and this is part of the work, and the research that we do to try and understand it so that ultimately not only can we catch it early, I'd love to prevent it, right? I'm working myself out of a job. That's the goal, right? Is to be able to prevent it.

- Well, we should maybe think of putting Goldilocks on the screen here. Not too much, not too little.

- Not too little.

- But do I need to actually break a bone, or to go into renal failure before I start treatment for myeloma?

- This is what made myeloma such a weird cancer for so many years, is that we said, because of this prevalence of MGUS, we said, you know, basically you can't define someone with myeloma until they have this so-called CRAB criteria. Their calcium is elevated, their renal, or their kidneys have been damaged, they have anemia, or a low red blood cell count, not enough red wine. I don't mean that literally and B, that their bones are affected, right? For reasons, complicated reasons, these bad proteins like to attack your bone. They come from cells that are within the bone, but they themselves can also attack the bone. So for many years we said you don't have myeloma until you have one of these CRAB criteria. But the reality was is this is different than most cancers because we typically define cancer by what we call the histology of what it looks like under the microscope. But it looks the same under the microscope. It was really just about the amount of it. And we don't wanna wait until someone breaks a bone to say that they should have treatment for their myeloma. So the analogy I always give Teresa is, you know, I'm a runner, although Sylvia, wherever she is, is making me cycle across Iceland. We're gonna hear about that recently. So my backside has been getting used to sitting on a bike for hours a day, which is lovely. Anyway, I love my Peloton . Anyway, if I'm a runner, I like to run, and if I'm running towards a cliff, hopefully Teresa will catch me before I fall off the cliff, right? Before a patient develops CRAB symptoms, we want to catch their disease early, right? And so we've also noted that there are other things that maybe you haven't quite hit the cliff yet, but if you have these things, and now they're called SLiM, or SLiM-CRAB. "S" standing for 60.

- Somebody brilliant must have come up with this.

- Yes, whoever came up with that acronym is absolutely brilliant, okay? No, 60% plasma cells, the ally or light chain means when we look at those light chains, we're gonna talk in a moment about how these bad proteins are both heavy and light chains. If the light chains are really high, it tells us that the kidney could be damaged very soon. Or if when we do an MRI and we look at the bone marrow, we see a certain kind of image that tells us that the disease is growing quickly. So what we've done now is instead of saying you have to wait until this damage occurs, if you're getting close to the cliff, then it's time to catch you. But this is a hot area of work and research, and understanding. I don't want to treat 5% of the planet with chemotherapy, but I don't wanna wait until someone is heavily damaged. We want to catch people in the right place. And we've learned, as you'll hear from me tomorrow, that sadly there are certain individuals who are at much higher risk of a delayed diagnosis. I bet you almost every myeloma patient in this room could share with me a story of how long it took to get the diagnosis made. The average person sees their primary care provider three times with signs and symptoms consistent with myeloma before the diagnosis is made. That's even longer if you're African American or Latino American, for lots of different reasons. But every individual patient is different. We want to shorten that time to diagnosis, and whether that's gonna be through a screening strategy, we're not sure yet. Whether it's great raising great awareness of understanding within the primary care world of what tests to order, and when to order them. These are the kinds of things that we're working on.

- Well, and that's a question that comes up so often is how is this not found sooner? Why were the blood tests that they were doing not showing that I had myeloma? Why is that? Why does it take a while?

- Yeah, it often takes a while because these tests that have to look for this unusual protein in the blood, it's just not part of our usual blood testing because myeloma's not that common, right? So until we can prove that we should be doing it on mass in millions and millions of people, we don't naturally test for it. The other reason is that the signs and symptoms that people present with myeloma are often very vague, and could be something else. I mean the top three signs and symptoms of myeloma are bone pain, fatigue, and a low hemoglobin or anemia. And there's 100 other things that can cause those three before myeloma on the list. So that's why we struggle with making the diagnosis. But when we do, we look at those basic blood tests that are typically done. That looks at the red, white and the rosé, what we call the CBC. The chemistry of our blood that also captures things like the calcium level, and the kidney function as we've described. And then we go into the specialized testing that some of you unfortunately have become experts in now where your serum protein electrophoresis, which just looks at all the proteins in your blood, and tries to identify if any of those monoclonal ones are there. And then the free light-chain assay. Because these monoclonal proteins are shaped kind of like a Y, but the short arms of the Y parts of them can break off what we call light chains. And about 20% of myeloma patients only have light-chain myeloma. So we have to look for both the light chains, and the heavy chains. And sometimes we even have to look in the urine because although the vast majority of patients can have their myeloma diagnosed, and followed in their blood, there are some patients that we can only find that abnormal protein in their urine.

- And I suspect we have to do some imaging?

- Absolutely. So when we talk about bone disease, in the old days we used to do a skeletal survey or a good Canadian boy that I am, we were trained to call it skeletal survey and those were just plain X-rays. Well those are helpful if someone unfortunately has a lot of bone disease, we can find problems with them. But now we've learned to do much more sophisticated imaging to catch much more subtle changes to the bone. So we typically do what's called a CT scan, or a low, a whole body low dose CT scan or a PET scan, or even an MRI because we wanna look for any of the damage that's caused. That's what's gonna make that big distinction between being MGUS or smoldering, and true active myeloma if there's evidence of bone involvement. And so we can, as you can see from the pictures here, see unfortunately the bone can be affected in lots of ways. Sometimes it's just the thinning of the bone, but sometimes it leads to a fracture. And one of the most common areas unfortunately are in our the vertebral column and so we'll see patients like in this picture where there could be actually a broken body there.

- And one of the favorite tests that people talk about is that bone marrow biopsy. Why is this so important? What do they do with this?

- Yeah, I wish we could stop doing bone marrows, and I think one of our research projects, the IMF actually is looking at reducing the frequency of bone marrow testing by being able to look for subtle changes in the blood. But going back to the analogy I gave earlier of the factory, you know, looking at those cars that have come off the assembly line tells me a lot about the factory, but it doesn't tell me everything. There are times that we simply need to be inside the factory. That's where the plasma cells live. Very occasionally plasma cells can escape the bone marrow. They're not supposed to, but they can. There is this phenomenon called plasma cell leukemia, which is basically just a very extreme version of myeloma where those plasma cells learn to live on their own. They don't need the bone marrow anymore. They don't need, you know, the supportive environment to the bone marrow, they can go off on their own. But we often do have to get those tests, do the test to get to the bone marrow. When we do get it, we're really looking for two major things. One, what percentage of plasma cells are there in that bone marrow? 'Cause remember by definition myelomas over 10%, there can be the occasional patient has less than 10, but that's for another day's discussion. And then secondly, not all plasma cells are the same. Not all cancer cells are the same. So one of the ways that we can distinguish them is by their, what we call cytogenetics. Now these aren't the genes that you have that you would pass on to your children, right? These are the genes that have been mutated in those plasma cells that have caused cancer. That's what we think, more often than not causes cancer is the cell, which is designed to live for a while and die off, goes through some kind of mutation and it lives forever, right? That's what cancer is in a sense. It's that identical, uncontrolled growth that we described that's sort of immortalized. And so in myeloma in particular, we can look for different genes that we think have been affected. And so you may remember that you get, you know, half of your chromosomes from your mother, and half of your chromosomes from your father. So you've got two copies of each of your chromosomes. And we know that there are on these chromosomes are kind of like codes for genes that actually enact the things that happen in our body. And so we can look for certain chromosomal changes that we know can predict, does someone have more aggressive myeloma, or less aggressive myeloma, or simply divided? We often call it standard-risk myeloma, and high-risk myeloma. Now they're not perfect. We know that these different studies can predict, and say, "Okay, someone has these, as you can see from the diagram, high-risk cytogenetic features. So they have a 17p deletion, or they have a translocation 14;16, or they have a gain of 1q." I know these look like funny letters and words to some of you, but those reflect the chromosome number. So if you have a 1q addition, it means the q arm of your chromosome 1. So chromosomes are built like a sort of X-shaped, at least how we we view them. And they all have what's called a p arm and a q arm. That's where that expression comes from. Mind your Ps and Q's, like, don't talk about my chromosomes that way. You know who said you can talk about my chromosomes, Deb? Like stay away from my, no.

- You're showing your your hematology geekness.

- I know I'm such a nerd, right? I'm sorry, I can win Trivial Pursuit games with you, so be careful. But anyway, so these, so the p arm is affected, or in some cases it's the q arm, or sometimes it's just one little gene. When you see the T letter, the translocation, it just means that one piece of a chromosome that's meant to be over here, and another that's meant to be over there get together. So translocation 4;14 means a little piece of 4 goes to visit number 14 at their house, and they have a little party together. But unfortunately that creates a scenario that can give the cell immortality, and allow it to be more cancerous. And so that's how we make that distinction. And I'm always cautious when I describe this because I don't want people to think if you've been given a high-risk cytogenetic diagnosis that it's a death sentence, right? We thankfully are doing so much better in treating myeloma, but about 25% of patients will have high-risk myeloma, and about 75% will have standard risk.

- So you talk about risk, we also know about staging. For people that are here, what would you say is most significant in pulling all of this together, and understanding the staging concepts, and the risk stratification?

- Yeah, so if you get diagnosed with any cancer, one of the first things that your family, or friends are gonna say is, "What stage is it?," right? Because we're sort of built on this solid tumor model where whether it's breast cancer, or lung cancer, or colon cancer, if it's confined to one area, it tends to be more treatable. But as it's spread, it goes to higher stage. So, you know, stage 2 breast cancer means it's gone a certain distance. Stage 3 distance, stage 4 means it's metastatic, and it's spread to other places. Myeloma's a bit more complicated because we're a liquid to begin with, right? So we're circulating everywhere. So it's not so much a proximity distance. So over the years we've developed different staging system, and it's no wonder that in lymphoma, and leukemia, and myeloma, the three blood cancers, we keep changing our staging systems, because it's just not an easy thing to do. The solid tumor doctors look at us and say, "We've had the same staging system for 50 years. You guys keep changing yours every couple years." Again, that's not to make light of it, but it's just to say it's complicated because we've come to learn that it's not so much, you know, as it's spread further. 'Cause these are diseases that just naturally flow. It's a question of those cytogenetics. And as we study the cytogenetics better, ever since the human genome project, we can now understand the disease better. So we have what's called the international staging system, and then there was the revised international staging system. Then there was the revised again staging system. Let me tell you, I'm sure there's gonna be an R3 and an R4. Like I would be less-

- It's like "Rocky."

- Yeah, exactly. It's never gonna stop. So I would be less concerned about the formal stage as much as, what are your cytogenetics in terms of have they put you in the standard-risk bucket, or the high-risk bucket? And that's generally how we look at it because that does have implications for treatment.

- All right, so as you mentioned treatment. Now we figured out with all the tests that I have a newly diagnosed myeloma, it requires treatment or recommended for treatment. I pretty much just have to have a couple cycles of chemo and I'm done right?

- I wish that were the case. That's our goal. Remember, I'm trying to work myself out of a job, but right now, when people come to be treated, we still generally divide people into these two categories. Are you eligible for transplant, or you not eligible for transplant? And that's based on the phenomenon that a so-called transplant is a good thing for myeloma. Now that's being questioned, and you'll hear about that. Dr. Lonial will talk about it, we'll discuss it. I'm sure it'll come up in the Q&A. With these new therapies like CAR T-cell therapy and so on. Are we gonna be replacing stem cell transplant? It's a little early to tell. But in general we make that distinction. Either way, people get some kind of initial therapy, and based on my first hot topic today. What was the first hot topic? Anybody?

- More is better.

- More is better. Okay. Thank you. Somebody was listening. It's like, but no, we talked about how we're offering now using four drug combinations off the start. Often it's the same whether you're going to transplant or not actually, but at some point the goal there is to what we call induce a remission, or it's called induction therapy. Because the idea is to get the disease down, and then that's followed by what we call consolidation therapy, which is basically to keep the disease down. And then there's maintenance therapy, which is to maintain the remission over a long period of time. Induction and consolidation is all about depth of response. Maintenance is all about duration of response. Which is why induction and consolidation tend to be intense things, because we really want to shrink down this disease. But maintenance therapy, it's so important that it's gentle on you. Some of us were chatting about maintenance therapy at the break because that's what's there for the long term. And as Yelak shared with us, I mean our goal is to allow people to live life to the fullest, right? And so maintenance therapy should not be harsh on your quality of life. And so that's where we have all these different terms. The last thing I'll say about transplant, for those who aren't familiar with it, you'll be hearing more from Dr. Lonial tomorrow, if you haven't heard much about it. Transplant is basically one big whopping dose of chemotherapy. That's all it really is. It's just trying to add another layer of damage to those cancer cells. But because it's so intense, it hits a lot of your good bone marrow. So prior to giving it to you, we collect from you what are called stem cells or cells that can grow a new bone marrow, like if you will, like seeds that could grow a new bone marrow. So we take the seeds or the stem cells from you, we give you that big whopping dose of chemo, then we give you your stem cells back to regrow the marrow. It's not curative, but we know that it can help put the disease into remission for longer.

- In your wine analogy, that'd be like the tequila .

- If you want to have some tequila, you can have some tequila .

- Be a heavy dose. So when we think about-

- Apparently we are not tequila lovers here, yes.

- When we think about the different treatment options, I mean Robin started to allude to this when she was doing the overview of the myeloma.org website, but we have a lot of treatment now available.

- Amazing. I mean when I started in myeloma over 20 years ago, there were maybe three names on this slide, and the next one total. And now look at all the drugs we have. This is not a remedial reading course, I'm not gonna read them all for you. And as you saw from the QR code, you can download these slides yourselves. But it's remarkable how many different classes of drugs that we've had. And as was explained before, you know, a drug has a so-called generic name, a medical name that we give it, and then it gets a trade name once it reaches a level of approval. And so we have all these different classes of drugs, and historically we've worked with the IMiDs or the immunomodulatory drugs, drugs like REVLIMID and POMALYST and the proteasome inhibitors, and then added steroids to it. So someone was asking me at the break, you know, steroids are, back when I started myeloma, often that's all we gave patients. We didn't have access to anything. We would just give steroids. So steroids have a direct anti-myeloma effect. They also reduce the risk of getting a reaction. They can also reduce nausea and reduce pain. So steroids are the drugs that we love. But we also hate it because for any of you who have been on steroids, and now I can look at your partners, you might be affected by it, right? Like it affects your ability to sleep, it affects your grumpy factor, it affects your blood sugar, your blood pressure, it does all sorts of badness. So later on at some point this weekend, we'll talk about the movement that we've created, the new hashtag Down With Decs. Where we're really trying to reduce the amount of decs. I think of decs like the booster rockets on the shuttle, really helpful for the first few cycles, but then we need to taper it down because it causes a lot of damage with time. But now more recently we've added monoclonal antibodies, we've added XPO1 inhibitors like Selinexor, and we've added these others that you're gonna hear a lot about this weekend in particular. Let me, I've already highlighted Belantamab, CAR T-cell therapy, and bispecific antibodies. And I shared with you earlier a little bit about how those work, and I think we've got a picture or two to help describe those later. But in essence, CAR T-cell therapy is different than stem cell transplant. Stem cell transplant. I take your seed cells or stem cells, give you the chemo, then give those to just grow your bone marrow back. CAR T-cell therapy, the collection may be similar, but now we collect T-cells or these soldier cells that can attack myeloma, and in the lab we manufacture them in such a way that they're going to attack your myeloma. And miraculously we multiply them in the lab, and we actually even give them back to you knowing that they're gonna multiply more when we give them back to you. And those, that's what's called CAR T, or chimeric antigen receptor T-cell therapy.

- So we-

- And there's a lot more to come.

- We get the therapy started, how do we know it's working?

- Right, so with any cancer you want to see it shrink, right? If someone has lung cancer and it's 10 centimeters wide, you wanna see that number go down. We don't have a simple tumor that we're measuring in myeloma. So we measure what was ever measurable at the start. Was it the M spike, or that monoclonal protein we talked about? Was it the light chain level? We also look at the percent plasma cells in your bone marrow. We may also look at the imaging. I've often said in my clinic, myeloma is kinda like a crime scene. There's no one piece of evidence that tells you the whole story. You've gotta look at the whole thing together. And over time we want to see all of those measures go in a direction that gives people, so-called remission. And so we have depths of that remission. So typically we consider someone a responder, if whatever measure of myeloma gets cut by half. That's called a partial response or a partial remission. If it goes down by 90%, which is a huge drop, that's a very good partial remission. If it goes down by 100%, it's a complete response. Doesn't mean cure, but it's 100%. And then we even have riders on that to decide how we define complete response, 'cause there's something called stringent complete response, et cetera. But then unfortunately we know that that's not curative, 'cause at some point the disease will come back. But we want to get people as deep as possible. That's why you're gonna also hear this weekend about MRD or minimal residual disease, which is where we barely find any bits of myeloma left. But sadly, even when people get into MRD negativity, there will likely come a time where the disease comes back.

- And that, I guess is the next question. How do we know when we need a new treatment?

- Yeah, and it's challenging because just because the number appears again or starts to climb, we don't necessarily jump on it right away because these numbers are fickle. We've all seen numbers blip back and forth. And going back to the same analogy, and running towards a cliff, I don't wanna wait until my patient gets really sick again. I don't want that M spike to go up to where it was before, and them to start breaking bones and damaging their kidney. So we want to intervene early. So that's why we often call it a biochemical progression, or asymptomatic someone to, "Hey doc, I feel well why do you wanna start treatment?" That's why you get blood tests when you still feel well. 'Cause we want to track that protein, and see if it's climbing. And then unfortunately, when it reaches a level that is truly climbing, we tend to want to intervene.

- So how do we attack that relapse?

- So this is this one slide. I know that it looks like alphabet soup to many of you, but one of the things that I said right off the start, we talked to hot topics, is coming at the myeloma in different ways, is guided by the great research that we've done in the myeloma community across the whole world in understanding myeloma. One of the things we've understood with myeloma is all of our cells, actually, in particular myeloma cells, have these things that stick out of 'em. Sometimes we don't even really know what they do, but we know it's something we can grab onto. And so these drugs that we've developed, the antibodies that tag onto it, the CAR T-cell therapies where the T-cell hooks onto it. The bispecific antibodies is prescribed, that grabs onto the myeloma cell, and to a local T-cell. They all have to find a target on the myeloma cell. And for many years we were very familiar with two targets, CD38, and something called SLAMF7, or used to be called CS1. But more recently we found three new targets on myeloma cells that a lot of these drugs use. One's called BCMA or B-cell maturation antigen. And the other is FcrRH5, and another called GPRC5D. Again, remember this is just to give you an overview. A lot more detail is gonna be coming over the next day around these things. But these now have served as targets for the different therapies that we have as we try to attack the myeloma cells, because these myeloma cells are smart. You know, I attack the CD38 antigen. I grab onto it, I grab onto it, eventually the myeloma figures it out. And the CD38 antigen or the antigen is just another word for target on the cell. When that CD38 disappears, now I can't grab it anymore, right? And so I need to come at it in a different way, and then that target runs thin, and then I need to come a different way. This is how the cancer evolves and begins to evade therapy.

- And we've evolved. Look at where we're at, where we're going.

- This is my favorite slide. I update it now literally every month because there are just so many drugs that we have in myeloma and it's not a perfect list. It continues to grow. But we've gone from 1, 2, 3 drugs in myeloma, to over 20 in the last 20 years. And using them in the right combination, in the right way, I think is gonna help us keep patients in remission for much, much longer.

- Now I'm gonna ask you the million dollar question. What about cure? What about cure versus control? How do we define cure?

- Yeah, it's a challenging way to think about it, but really important, right? So historical use to say there are two kind of camps of thinking in myeloma. Are you in the cure camp? Are you the control camp? Right? If you're in the cure camp, right? Let's just completely devastate this disease. Let's give someone as much treatment as we can. This was exemplified in Arkansas, that developed a program called the Total Therapy Program. They would give people three transplants, and every drug that they've known. They would just try to whoop this disease as best it could. And for some people it may have enacted a cure, but for a lot of people it gave a lot of toxicity, a lot of side effects. The control camp says, "No, no, no. Myeloma's kind of like high blood pressure. We're never gonna cure it. We'll just control it. Let's just give the minimal amount of drug to keep it in check." Well, the reality is both extremes are not the way to go. It's somewhere in the middle. We're probably leaning a little bit more towards the cure side now, but what is cure to you maybe defined differently by someone else. I think of cure as being when you treat someone, and they never have to think about the disease again. And we're not quite there yet. Maybe just taking a pill like you do for high blood pressure is gonna be enough for the rest of your life. But we do see a much larger fraction of patients living longer. When I started in myeloma, the average survival of patients was between one and two years. Now the average survival is over a decade. And for many, as we've already seen today, it can be considerably longer.

- Yes.

- That being said, I do also just wanna be realistic that there's still, I just, sadly, I had a patient who died less than six months after his diagnosis. So there are still forms of myeloma that are extremely challenging to deal with, but overall that curve that you're seeing, meaning how many people are living five years, and beyond continues to grow. And I think it'll continue to get better.

- All right. Well I think we've picked your brain enough for this moment. We're gonna come back and do that again later. But I think Dr. Joe did a great job answering these questions and the answers to many of these questions not quite as eloquent, are available in a lot of the publications. So thank you.

All right, everyone, I'm Danielle Doheny. I met a lot of you earlier, but for those of you who don't know me, I'm the Director of Public Policy and Advocacy for the IMF. Basically, I am the federal lobbyist for myeloma patients. Everybody has a lobbyist and myeloma patients need one too. But I'm going to talk to you today one, about what advocacy is, why it's important, and why you might want to get involved with it. And then I'm also going to talk about some important changes to Medicare that are coming up that anyone who is in Medicare should pay attention to, because there's some big changes that actually we advocated for, but there's some caveats that we'll all kind of need to know about to make sure that you're taking advantage of the changes. So what are the things we advocate? There are kind of three buckets there that we'd advocate for. First and foremost, access to care. So there's a lot, as Dr. Joe was mentioning, a lot of new medications out there that are amazing that have changed the lives of patients everywhere. My dad being one of them, that's why I got into this myself. But we want to make sure that people can access these, that just because they're there doesn't mean everybody can have it. We want to make sure that that's not the case. We want to make sure that any person who has myeloma can get what they need. Number two, financial barriers. We know a lot of people have issues affording their medications, so we want to make sure that that's something that isn't happening to people. And the third one, research funding. That's a really big one. We want to make sure that this progress continues and we really want to make sure that, I mean, it's very, it's a passion of mine to find a cure for myeloma, and not being a researcher myself, advocacy is a way that I can contribute. And this is just a little bit of a bigger picture snapshot, just so you can see some of the things. In that access to care bucket, we have something called insurance reform. That's things like step therapy where you or your insurance company might say, "Hey, you have to try this drug before you can have this one." And your doctor might be like, "Well, I know that's not going to be the best course of treatment for you and you have to fight the insurer." So we are trying to make sure that you don't have to fight insurance companies to get what you need. Also, telehealth and telemedicine, we want to make sure that that is robust and available for patients. We want to make sure people can get that. And then oral parity, I know a lot of you probably have noticed that your out-of-pocket costs for like your Revlimids and your Pomalysts, things that you're taking at home are a lot more expensive than what you're taking in office. And we don't think that that's okay. And we work with a lot of other cancer groups on this. We're not the only ones. So we run a coalition on that one. And Medicare reform, this is a big one. We hear a lot of access issues from our Medicare patients, so that's something we advocated really heavily on. And then in the research funding, there's just several buckets that we advocate for there. And within that, we include clinical trial diversity. We want to make sure that anybody who wants to participate in a trial that's eligible was able to do so, that there aren't barriers there. And I think a lot of people say like, "Well, why would I want to do this?" Or "Why does this matter to me?" That's where I want to present to you today and really just tell you the why. I have pictures here of several of our patients that have come with us to Capitol Hill. So legislators don't really move or make changes unless they hear from people. I can come to them all day with sheets and sheets of facts and figures, but until they hear the story of somebody that really humanizes something to them, they're not going to make a change. I used to work in a congressional office as a staff member and people would come in and sometimes everyone in the room would be crying by the end. But you can bet that absolutely, I would make a recommendation to the member of Congress I worked for to support that person's bill that they're coming into me to talk about because it's important. And I think without that personal story, no one is going to know how important it is to make that change. And I think you might also be asking yourself, a lot of people are like, "Well, I can say stuff all day and no one's going to change anything." I just wanted to talk specifically about those Medicare changes because those are something we advocated for a very long time. And it happened. That wasn't just the force of IMF, that was the force of every disease advocacy group in the country coming together and saying, "We want this." Medicare created an out-of-pocket cap for drugs. So starting next year for your plans, no one who has Medicare will pay more than $2,000 over the course of the year, so that's because of advocates, people like you who came and said, "This is a problem, I can't afford my medication." Or this is just from having to go to all these copay foundations and see who has money. And it's just really devastating to my family. So those stories were shared. So I'm just going to talk a little bit about what those changes are. First and foremost, some of these have already started like no copays for vaccines, insulin copays that are lower, and then 2024, there's something called the extra help program that I recommend to everyone to look in and see if you might qualify for that, because that's going to be a big relief to a lot of folks. But I think a lot of people don't realize that they qualify for it one and two, it's a really big percentage of people who will qualify. And I think the thing that's really important, Medicare won't automatically enroll you. So you could potentially take advantage of some of these benefits such as like lower out-of-pocket costs and not even know it. And then in 2025, the big piece that will be amazing for everyone, that out-of-pocket cap. And this is one thing that I think is really important for people to know about that there's something else we advocated for in there called the Medicare Prescription Payment Program, or they call it the MP3, it's ridiculous, I know. But it's basically a mechanism where you can smooth those costs, they call it smoothing mechanism where you can take those costs as spread it across the course of the year. So instead of like $2,000 in January, you can have payments that are about like $166 a month, but you have to opt into that, you have to go to your Medicare plan and then sign up, and we as advocacy groups are really trying to push that out to people because I've presented to a lot of support groups on this now and not one person has known that this is a benefit that they can take advantage of. So it's really important. We have some points there that I think just folks need to know. So you just have to know that you have to opt into the program and then two, know that you're going to pay so much less next year and we're really excited about that. It used to be there was no limit and you could just pay, pay, pay. And now 2,000 over a year for drugs, it's going to be fantastic. And I just wanted to put this other slide in here just to show you. It's from "The Wall Street Journal," it just shows the difference in cost from this year to what folks will pay next year, everyone paying 2,000, and they just, as somebody who has like a parent who has been on these drugs just to see this, makes me so happy and it just really shows that advocacy matters. So this will be something that we can all take advantage of in the future. And I wanted to show a little bit of what we do, just a little bit of some of our successes, we've successfully advocated for some research funding and I've got some of the programs that we have had that success in. We've brought some patients in to do a congressional lobby day with us, and it was the American Cancer Society was the lead on this one, but they brought people in just to ask for increased cancer research funding overall. And it was a great experience for our advocates. If that's ever something you'd want to do, we would love to have you, sign up with me or talk to me more about it. Then also, we had a congressional briefing just to educate staff on a lot of these issues that people are having. specifically the one we call oral parity, but that's the one that has to do with the oral oncolytic costs versus the IV. And we had people talk about "I can't afford my medicine." Or a man who came and spoke about how he had to, he couldn't sign his kids up for the sports he wanted to because he was going and their family maid was going to his medical care and how much of a difference this would make. So they also met with staff on congressional committees and a big dream of mine ever since I started here would be to have an IMF lobby day where we would bring our patients in, anybody who wanted to, and they could come and tell their stories. That's basically advocacy is is telling your story. I want to also make that clear. Like you don't have to go in and say, "I know all about this policy." What you're doing is saying, "I have myeloma and this is how I was diagnosed. These are the challenges I've faced." That's all they need to know. So I'm really excited, hope you'll join us. Do we have time for questions? Do you guys know? Yeah, yeah. If anyone has questions about advocacy or about the Medicare changes, I'm happy to take them. Okay.

- [Attendee] Danielle , I think it's fantastic if people write down the website where they get called.

- Oh yeah.

- [Attendee] Like so your contact information.

- Yeah. So up with, yeah, up at my booth I have a QR code that folks can take. And I also have a sheet you can sign up on. So go ahead.

- [Len] So my name is Len, had myeloma for 13 years now. Thank God all is good. I have a question for you. You mentioned the 2,000 out of pocket next year. Does that mean the donut hole will disappear altogether from Part D?

- It does, yes.

- Good.

- Yeah, that was something that we heard from a lot of people was a problem. And also you reminded me if anybody has things they want to see changed, come to us 'cause we will be your advocate.

- [Attendee] Basically the same question about the $2,000 deductible for Medicare. I was wanting to know what if you don't have Part D?

- So if you have an advantage plan, it applies there, but it's only Medicare, so it's Part D and Medicare Advantage, it's their drug plans too. So it encompasses that as well. Does that answer your question or?

- [Attendee] I can buy just regular Medicare.

- So you would have to have like a Medicare Part D and have like have the drug insurance coverage as well. So it's any, yeah.

- [Attendee] I see.

- [Attendee] Hi Danielle, question on, I just saw that the, there's 10 drugs that were approved through this new Medicare thing. I noticed that one of them was a blood cancer growth for leukemia.

- Yes.

- [Attendee] Anything in the works for myeloma?

- Yeah, so those, the first 10 were the ones that Medicare selected. We should get the next 10, I think it's in a few weeks actually. So we will be able to see if there's some medic, if there's a myeloma one there. We won't know the answer until Medicare comes out with those next 10 though.

- [Attendee] Hi Danielle, first of all, thanks for your work in the advocacy role. Very much appreciated. My question is, am I hearing you correctly about 2,000, about this year, 2023, and also, excuse me, 2024 and 2025 that we must opt in with our Part D pharmaceutical coverage?

- Yes.

- [Attendee] You have to call them and opt in?

- So everybody will get the 2,000. The opt in is for the ability to make those costs not all in like January. It would be like to spread it over the month, the course of the month.

- [Attendee] Thank you, is it too late to opt in for 2024?

- So 2024 doesn't have it yet. So this is, yeah, this is for the next plan year.

- [Attendee] For the next, thank you very much.

- [Attendee] Hi, I have a question. Thank you, thank you for your advocacy. I purposely did not sign up for an advantage plan, and I got a separate prescription plan, WellCare. Can you buy Part D separately? And you mean would I have then to Part D or do I have to join an advantage plan?

- So do you have traditional Medicare?

- [Attendee] Yes.

- Okay, so traditional Medicare and is WellCare is not a Part D plan?

- [Attendee] Pardon?

- So WellCare is not a Part D plan?

- [Attendee] It's a prescription plan only.

- So if it's a prescription drug plan for like Medicare recipients, my understanding it would be-

- [Attendee] It's separate than Medicare.

- Okay, I'd have to look into it. If you meet me back at the table and give me your info, yeah.

- [Attendee] I just wondered if you knew, I think all of this is so new that-

- It is.

- [Attendee] There's going to be a lot of questions. So I just, I really appreciate this.

- And we actually have an open line with Medicare as well, so if it's something that like I don't know, we can always ask the program managers too, like.

- [Attendee] Yeah.

- Good for time or?

- [Moderator] Other questions? Hot topic, right? Lots of hot topics today.

- Okay, thank you very much. If anybody has questions afterwards, feel free to, I'll be out in the hall.

- So one of the things that... I'm sorry, it's me again, but this is the last you'll hear of me today. So one of the things that we wanted to spend a little bit of time going through also to prepare you for the discussion that will be coming. But also just in general, clinical trial awareness is something that we felt is particularly important. I'll discuss this a little bit tomorrow. We talk about health disparities and some of the disparities in trials, but a little bit like when we did the 101 with Theresa, instead of just having Dr. Joe wah, wah, wah, like Charlie Brown's teacher, we're gonna try and do it as a little bit of a back and forth. So I'll turn it over to the boss.

- Give you the mic.

- Sure.

- I'm going to stay here.

- [Joseph] Sounds good.

- That way, I can actually have the clicker as well. So today, we are going to talk about clinical trials and we have three objectives. One is provide the rationale for clinical trials, right? The second one is be able to outline the phases of clinical trials and then discuss the risks and benefit of clinical trials. But before we go into that, I'm actually going to take us back and forth. One of the things that Dr. Joe, that you say and other experts say is that you should consider clinical trials as part of your care. What does that mean in English?

- Yeah. So what it means is that clinical trials aren't some kind of completely different phenomenon than what you're receiving on a regular basis for your care. We wanna, if you will, normalize the concept of a clinical trial. Sometimes people hear clinical trial, they think like, I guess, I'm gonna be some kind of experimental mouse that's gonna be put into a maze somewhere and I don't know if I'm gonna get out and it's gonna have all this weirdness to it. You know, part of the reality is that the very place that the vast majority of people get their clinical trials is the very same place that they're getting their regular care. Or if not, it's very similar to it. So I think in principle, Yel, the concept is to say clinical trials are part of the natural process of care and we don't want it to be viewed very differently. That being said, we want people to view it differently enough to recognize that it plays a unique role in the way we care for patients and it gives people an opportunity to have access to treatments that they would otherwise not have access to.

- So for me as a patient, when I come to you and I say, I may be progressing or if I progress in the future, what clinical trials are available for me as part of my care should be one of the standard questions I should ask you.

- Absolutely. So, whenever we're looking at options of treatment, we almost always have a standard of care option, but we also may have a clinical trial, whether it's newly diagnosed, early relapsed, or have had 10 different treatments of myeloma before. That's where we tend to think of more clinical trials later on, where people have run out of other options. But don't think of clinical trials as only being the so-called Hail Mary pass when everything else has failed and you have no other choice. We wanna think about as choice all the way through, so that people can have an opportunity to participate even in earlier line therapy.

- So earlier, a few minutes ago, you brought out this word, guinea pig. So clinical trial is a word that is used to hide the fact that this is making patients guinea pigs and it is dangerous and we leave the patients broke, right?

- No. So hopefully, the answer to that is no. So the idea is never to make someone a guinea pig, per se, right? So we're gonna be talking a bit more about drug development as we go through. But being very pragmatic, and I hope it's okay to use this word, I'm saying I want you as a myeloma patient to be selfish, right? I want you to have what's best for you, 'cause sometimes people think, oh, if I'm gonna go onto clinical trial, it's because I'm kinda donating my body to science or I'm gonna help other myeloma patients in the future. Well, it's not to say that there may not be some trickle down effect to others, but it really should be about you. Is this something that would be valuable and beneficial to you by getting earlier access to treatment, by getting something in addition to the standard of care to potentially getting something better than what's currently available? It's not that someone's giving you some kind of placebo, we would never do that in myeloma. We can't ethically. We have to, at minimum, give you what is the standard of care. And very often, it's a question of adding something to what we would normally give. You know, we've learned that this combination works really well. Kinda like I shared earlier that three drug combination of VRd, Velcade, Revlimid dexamethasone has been used for many years, has been very effective. Can we make it better by adding Darzalex or Sarclisa to it? And we learned, yes, we could. There's no way we would've learned that had we not done it in the context of a trial. So if someone goes on to a trial like that, they're at least getting the VRd if not getting the VRd plus something else.

- You mentioned earlier, over the last 20 years, close to 20 drugs have been approved for the treatment of multiple myeloma. Which one of those drugs haven't gone through a clinical trial?

- None of them. They've all gone through clinical trials. So I see the sarcastic tone, I love it. But, you know, that's exactly how drugs get developed and we'll talk through the drug development in a moment and how we get there. But every drug must have gone through clinical trials. We study things in the lab long before we bring them to patients. We study them in cell lines as we call them. So I can have, in my lab, we have like a culture of cells that are mimic what real myeloma cells are like in the body. It's not a perfect example of what, you know, you can imagine that in a car research facility, right? They're testing out tires and they're putting them through all sorts of tests. The tire is not on the vehicle at the time. They're testing it in a test tube as it were or in a place to see if it has validity by itself. And then they'll test it on a car in a similar capacity. We've put these drugs through a lot of tests in the lab before we ever bring them to patients.

- So what I'm hearing you say is clinical trial is part of the normal drug development cycle.

- Absolutely. So that cycle, which we see a little bit outlined here, is starts with... Remember how I showed you that picture of the myeloma cell with Theresa and we saw all the different things sticking out of it. We wanna learn. We can't develop a drug for something we don't understand that what we're attacking. So that's why so much research goes on in trying to understand and characterize what does this enemy myeloma look like? What does the cell look like? Where might the cell have its Achilles heel, right? Where can we attack the cell? Where can we get it? And so we identify these concepts or targets as I've listed here in the lab. And then we wanna see if we can actually prove that. We test, as I mentioned, in cell lines or in animal models, because believe it or not, you're a lot more like a mouse than you might think you are. We actually have a lot of similarities, genetically speaking. I know it's a little creepy, but it's true. Genetically speaking, we're quite close to them. And then once we've tested that, then we can now bring it into to a larger patient population.

- So those are the preclinical trial, the clinical trial, and then the drug development portion, right? What are the various phases of clinical trials?

- Right, so when we talk about the phase of clinical trial, we classically talk about phase one, two, and three, and to some degree, four. But even before phase one, we do have some things that we have to do. And as I've mentioned, this is where we test in the lab, where we work on it in animal models or in cell lines where we want to see is there any evidence that this compound, this drug is actually gonna damage myeloma cells and prevent their growth? And then we bring that very first phase one clinical trial, we call a first in human trial. In the clinic that I have in Arizona, this is what we focus in on. I've had the privilege of doing several of these first in human trials where we've tried a new drug that has never been used before. But when we come to phase one, the concept here is a little different. This is what's important. This is where sometimes I think people have thought, oh, am I just a guinea pig? First of all, you're clearly not a guinea pig, but the concept of a phase one trial is the very first time we bring it into humans. if there are three words I say repeatedly in my clinic when the students and residents work with me is safety is paramount. So the FDA guides this, it's under very careful protection. Safety is the most important thing. We wanna make sure we're not overdosing people. So we typically have to start very low dose. So it could mean that if someone's going onto a phase one trial, they're gonna get a very low dose of the drug. A lot of our trials allow that same patient to get a higher dose, assuming they tolerate the first dose well. So the focus of phase one is not so much, is the drug working to kill myeloma cells as is the drug safe? And at what dose should I be giving this drug? So if we think a drug's gonna work at 10 milligrams, just to keep it really simple, we might say the very first patient we treat with this drug, we're gonna give them one milligram, sometimes even .1 milligrams, because that estimate for 10 may be way off. And I've developed drugs where we thought it was gonna be 10 milligrams, it turned out to be less than one was the right dose. So we start low and then we move up relatively quickly over a few patients to get to the dose that we think is gonna be effective, and we wanna make sure that we characterize that it's safe. That's the essence of a phase one trial, which leads it to a phase two trial where we say, okay, you know what, 10 milligrams seems to be the go-to dose, but now we've only treated half a dozen people with it. Now, let's do a trial of, let's say, 60 patients who get that 10 milligrams. Now, we're focusing on how effective is the drug. And some trials will have a system where we don't put all 60 patients on right away, right? We put on several a time. And if out of the first 15, we don't see responses, we may have to abandon the study. On the other hand, if we see lots of responses early on, we may increase the numbers to even further confirm the fact that the drug is working well, and that becomes the phase two trial. Most phase two trials are what we call a single arm. You're not comparing one treatment strategy to another, you're just introducing this new treatment. But ultimately, the mother of all trials, as it were, is the phase three trial. And that's where you say, look, this drug is working so well at that 10 milligrams, so many people are responding to it. Now I'm gonna compare it to the standard of care. So is the standard of care this other drug? So let's see we do this other drug versus this other drug plus this new one versus just the old one to see is this new drug adding to it? There are different ways that we can design trials, but as long as the people in the so-called control arm, the arm of the standard of care are getting clearly the standard of care and then the patients in the intervention arm are getting the standard of care plus something new. That's typically how we do a phase three trial. And these ones are much, much larger. These are typically hundreds of patients that need to be on this trial. And this is the trial that ultimately leads typically to approval of drugs.

- But there are also drugs can be approved with the result of phase two clinical trials in an accelerated mode.

- Correct. So I mentioned this briefly when we talked about belantamab earlier, that there is this accelerated approval. And, you know, Danielle beautifully described the importance of advocacy and so on. This has been advocacy in the cancer community for many years of saying, if we only wait to get a drug approved after it is completed a phase three trial, may give you a sense that I helped develop that the drug that we now use Sarclisa, led the first in human clinical trial. And that was over, let me see, that would've been 13 years ago where we did that first in human study. And it was only a couple years ago that we really completed the large phase three trial. So we would've had to make patients wait 12 years essentially to get access to this drug. So the FDA has said, okay, in that early phase two trial, after you've worked out the phase one, you worked out the dosing, in that first trial that you did of 60, 80, 100 patients. If there's enough of a signal that the drug is working, we will give it approval, sort of, if you will, a conditional kind of approval, saying, we'll prove it, but you need to go on and do the phase three trial. But patients in that interim get access to the drug. And that's what becomes really important. I mean, maybe the most important lesson if you're, you know, busy on Instagram right now or doing whatever else, you're not really listening to me, which is fine. But if there's one thing I really want you to listen to is the fact that the key of clinical trials for the patient is to give you access to something earlier than when it's fully approved. It's not just about helping others, that's a noble and lovely thing to consider. But getting that access early on, and very often, getting that access early on saves lives, because by the time that phase three trial is done, that patient may not be with us anymore, who would've had access to it. So that's the key of being able to get accelerated approval.

- So Dr. Joe, before I ask you to summarize the three phases of clinical trials, you mentioned during phase one, one of the goals of phase one is to be able to find out what is the maximum tolerated dose of a drug, right? Earlier when you're having a conversation with Theresa, you mentioned about the side effects of steroids. Use steroids, the four days on, four days off versus the current practice. And talk about what is the difference between the maximum tolerated dose and the minimum effective.

- Yeah, the phase one community outside of myeloma, even just in cancer is questioning this old adage that I shared earlier that that more is better, right? That you just wanna give as much drug as the patient can handle 'cause it's gonna hit more cancer cells. That's what we call the MTD or the maximum tolerated dose. So in that phase one trial, as I tell, we tested at .1, we tested at one, we tested at five, we tested at 10. Oh, 10 is the maximum tolerated dose because we learned that at 10 people, maybe we even went higher to 15 and found, oh my goodness, at 15, there was a lot of side effects, so we come back down and keep it at 10. But just because 10 was the maximum they needed, maybe they don't need all time, maybe five was actually enough. And this is the kind of work that we're trying to do now. And sadly, sometimes we just do, we end up figuring it out later, right? As I commented earlier, almost every drug in myeloma now, we give it a lower dose than the way it was first approved, because it was built on that maximum tolerated dose. And the reason why we focus on this so much, one is not just to affect the way we develop drugs, but also to reassure you, 'cause I've had patients say to me, you know, "I heard, doctor, that the clinical trial used 25 milligrams of Revlimid, but my doctor gave me five. Why is she only giving me one fifth of the dose?" Right? These drugs don't work in that simple way of thinking that five is one fifth of 25. It's not that simple. It's the way the drugs interact with us. And so we're learning now that often we can use lower doses of drugs. And this becomes particularly important when we start combining drugs together, because maybe you need just a little bit of this and a little bit of that. Now, sometimes people take it to an extreme and they're like, here, just smell these six bottles and then leave, right? Like, you know, we're not necessarily giving homeopathic doses of these drugs, but we are trying to find the minimally effective dose, meaning what's the lowest amount that I can take, but still have benefit.

- So I don't know if it is intentional or unintentional. He avoided my question about steroids. So when I was treated for myeloma in 1995, I took 40 milligrams of dex every day for four days, took a four day break and came back on 40 milligrams of dex for another four days. I basically lived next to the refrigerator and I was a little bigger than I am right now. But over time, there was a clinical trial that was initiated as input by a patient, Mike Katz, who some of you may know, who was a board member with the International Myeloma Foundation. And he challenged one of the physicians and asked, "You guys talk about creating clinical trials for new drugs, but how about for steroids?" And they actually tested, and I'll let you speak about the output of that.

- Yeah, it's an incredible story. One, because I just loved Mike Katz, incredible. And now, Jason, his son, sits on our board. But it was one of the earliest examples of patient engagement and patient involvement in research where we have a group of institutions that work together to do clinical trials called ECOG, the Eastern Cooperative Oncology Group. And now, Yelak sits in that position. And the patient, Mike Katz, at the time said, "Look, can't you guys do a trial that involves us getting less dexamethasone?" You know, if you didn't fully catch what Yelak said, you might think 40 milligrams of dexamethasone every week is a lot. That's four days a month. These patients got 12 days a month of 40 of dexamethasone, four days on, four days off, four days on, four days off, four days on, seven days off, started all over again, right? That's how I initially treated people with myeloma when I was a myeloma fellow 25 years ago. We would just write them all that dexamethasone. And so Mike, at the time said, "Look, could you do this?" And so in conjunction with Dr. Rajkumar, who's now actually the chair of our board, as many of you would know him from Mayo Clinic in Rochester, said, "Okay, well, let's do this study where we give Revlimid, same dose of Revlimid to both arms, but we'll give high dose dex in one and low dose dex in the other." And that's what led to now us giving this low dose dex or 40 milligrams, a low dose dex. 40 milligrams once a week is still a lot, right? So now, we're looking at doing trials with what we're calling lower dose dex, eventually lowest dose dex. But, you know, we find that Goldilocks in the middle, where we're giving the right amount of dose. So it's an amazing story of not only how drugs could develop, but how the patient voice makes a difference, 'cause patients were saying like, this may be working, but look at all the challenge we're having. And by the way, what was interesting in that clinical trial, it wasn't just that the lower dose of dex was as good as the higher dose, it was better, because more people died from steroid side effects in the high dose dex than in the low dose dex arm. So it taught us that some of these drugs are harsher than we first thought.

- So I'm not sure I may be invited to ask Dr. Joe questions in the future because I'm completely off-script here, right? So you-

- Shocking. Shocking that you're off-script, right? I don't know if he's ever on script, but okay. You mentioned ECOG, what is ECOG? And are there other bodies like ECOG within the US? So that question number one. And question number two, another board member who's a boss of mine is in the back over there. She's from Canada, province called Canada of the US.

- Now, those are fighting words, man, so watch out. I might be moving closer to you now.

- So do clinical trials also happen outside of the US?

- Yeah. So two great questions. I love you, Martin, and I always will, right? I'm a duel citizen now. It was tough during the Olympics, by the way, because my wife's American, right? So when Emily's in the room, I'm like, yay, go America. Soon as she leaves, go Canada, go Canada, right? And we did pretty well. Canadians did pretty well this year. Yep. And not just when it involves ice and snow. So it was quite good. So to answer your first question, ECOG or the Eastern Cooperative Oncology Group. So there are several across the countries, alliance, there's SWOG, there's transplant groups. The whole idea here is every institution, you know, likes doing clinical trials. They wanna provide those options to the patients, right? I've had the privilege of working at Mayo Clinic. Now, I'm within the City of Hope Cancer Center System. I had privilege of working different places and those individual institutions can do a lot. But sometimes you want multiple institutions to come together to do trials because no one institution is big enough to do these big phase three trials. And that way is a lot of collaboration. It also provides greater sense of diversity geographically by race and ethnicity depending on where the sites are located. So there are multiple of these groups, they're often called cooperative groups meant to be sort of collaborative, cooperative groups. And yes, absolutely, if anything in myeloma, we've seen unbelievable outcomes from clinical trials all around the world. The Canadian Myeloma Research Group that was created by Myeloma Canada, that Martin has the privilege of leading, have actually done some of the most important studies in multiple myeloma. We go overseas. We see that in Europe in particular, a very strong myeloma research groups in Spain and Italy and France and the UK. And then, of course, the IMF has created under the leadership of Dr. Durie in the past now with Wiju Chung. We have incredible number of clinical trials that are now opening in Asia. We've just created a network in Latin America called the Latin American Myeloma Network. And so there are trials that are done really all over the world. It's not just about God bless Merca. There's a lot going on elsewhere. And that's really important because we wanna make sure that these drugs are not only developed in multiple countries, but they're applicable to different countries, because we are seeing, as I'll comment tomorrow, even with these new CAR T-cell therapies and bispecifics, there are differences by race and ethnicity and geography in the way these drugs work and in the way they cause side effects.

- Thank you. So I will call out Todd Kennedy here. He's also a patient advocate with Alliance, I believe. And so ask me, ask him what it takes to be a member of one of these groups and be able to advocate on behalf of other patients. I have one other question.

- Sure.

- Before I ask you some... Or I guess two or three. So when I went to myeloma treatment, initially, I was in Dallas. I moved to Arkansas and I got my CAR T in a semi-clinical trial setting called expanded access here at City of Hope. We also have a patient here from Harrisburg, Mississippi, Ken Oliver, in the back. And he may not have access to clinical trials in his area, so he may have to go to other places, Mayo or other places. So if a clinical trial is initiated at City of Hope and someone else is participating at that same clinical trial at Mayo or other places, are the clinical trial designed how I get treated, how I get tested, how I get the drugs, is it the same or it depends on who my doctor is?

- Yeah, so it's a great question. So two ways to answer that. So answer number one is if it's the same clinical trial, we set very careful parameters around how patients are treated, 'cause we don't want them treated differently because they're at one site versus another. So if Mayo and City of Hope are sharing a clinical trial, those patients have to be treated the same way. That being said, we also... And in COVID, if one of the tiny silver linings of the hideousness of COVID taught us was that even from a regulatory standpoint, we need to build in more flexibility. You know, it used to be that for clinical trials, your blood work had to be done on this exact day at this exact lab. And we started to build a bit more flexibility into the system, especially when it comes to geography, because if someone lives in a more remote area, it may be harder and harder for them to access clinical trials. So we are also trying to be more flexible. There's a whole movement of what we call DCTs or decentralized clinical trials where we're trying to say, okay, well, maybe at the big academic centers, we need certain trials, but can we do them out of the community? Can we have satellite sites? 'Cause it's not fair that if someone, you know, here, of course, in urban Los Angeles, you have multiple places even in myeloma to go for clinical trials. But if someone lives, you know, considerably up the coast and they're far from Los Angeles, can they still get opportunity to be on trials? And so we're trying as much as possible to be able to have that flexibility. So it shouldn't just depend on, if you will, who your doctor is. It's partly the design of the trial. And this is some of the, I know we'll come to it later, the pragmatic things when you talk to your doctor about whether they provide the trial or they can send you to a site like here in Los Angeles. As I mentioned, there's Cedars. We're gonna have Dr. Viseo join us tomorrow. We've got City of Hope as we've mentioned. There's USC, there's UCLA. I mean, there's so many different choices here. Whether you're with the your own doctor or at one of these sites to ask very pragmatically, how many times am I gonna have to come in? Do I need any other additional testing that I wouldn't normally have? What are the financial implications? I know we'll talk more about that in a minute too. But usually, we try to ensure that there isn't a financial burden to patients, because if you're gonna receive standard of care treatment, that should all be covered in the normal way.

- So when patients normally think about clinical trial, they expect some sort of intervention, but are there also observational clinical trial? And is there a great example of an observational clinical trial that you can think of?

- Correct. So yes, you're right. When you think clinical trial, you think I'm getting a drug or I'm getting an intervention or a vaccination or whatever it might be. But we have lots of ways of collecting information. You still have to give consent because it's your blood, your results, whatever it may be. A lot of times, we have non-interventional trials that are people just enrolling to have information collected. Or next time we do your bone marrow test, can we take a small sample and take it into our lab to do this and this study on it? That's really important to us because without that, we wouldn't understand, you know, how different myeloma is in different in people. One of the ones that I can think of, Yelak, as being a great example of a non-interventional, if you will, clinical trial is what the IMF is doing in the immune therapy registry. So you're gonna be hearing about CAR T-cell therapy, bispecific antibodies, that other drug I mentioned, belantamab, these are all new drugs that we're learning a lot about them. I mean, even if you're in a center that treats as many patients as anyone else, there's still a lot to learn from each other. So if only we could pool that information and data to understand it. You know, we, for example, sadly, see that there's a small fraction but an important fraction of patients that have some very unusual side effects from some of these drugs. Some of them are, for example, neurological side effects. So if I treat a hundred patients with CAR T-cell therapy this year in my program, I may only see one patient that has this unusual side effect. But if I pull the information with 40 other myeloma sites, now all of a sudden, we've got 40 of these and we can understand it all the more. And so the IMF has created what we call this immune therapy registry where de-identified information from each of these sites can be pooled together. And then we have this big database that we can interrogate and we can ask questions that no one would be able to ask. Right? Again, I don't wanna sound like I'm being a commercial for the IMF, but that's the superpower of the IMF, right? Is bringing people together in a way that otherwise that information would not be accessible. That we're like the Olympics convening people together, so they can perform at their top level, right? And that's why so many records are always broken at the Olympics, 'cause there's something about being in that environment, being with others, we wanna create that kind of concept. So there may be situations where your doctor will speak to you about a clinical trial as it were or a study, they may call it that, where they're not expecting you to receive a drug, but just be your information is being collected to put into a registry. Or you may fill out a survey every month as to what your quality of life is like being on a certain drug or not being on a certain drug.

- So why don't you quickly touch on what a phase four clinical trial is and I'll ask you to summarize the benefit of participating.

- Right. So a phase four trial is actually beyond, as you would expect it, beyond the phase three trials. So phase four is when we're collecting now information, in, if you will, the real world setting as we start to see what happens when it goes out into the real world. And it is actually amazing how many times we have learned things that we wouldn't have seen in those individual trials. You know, some of these myeloma phase three trials have 2, 3, 400 patients in them. Even then, that may not be enough patients to fully understand some signals. So in summary, phase one clinical trials is small number of patients, right? Finding the right dose to make sure that we know the drug is safe. Phase two is based on that dose, giving it to more patients to see how effective it is. Phase three is comparing it to the standard of care to see if it exceeds it. And phase four is analyzing and evaluating the intervention once it's already made itself into the public

- And quickly, benefits and risks.

- All right, so why would you do a clinical trial? Well, the greatest benefit is that you might have access to a drug that you otherwise wouldn't, that can control your myeloma and give you longer and better life. That's always, always the objective. Very often, as I described earlier, it's that the trial is being done before the drug is formally approved. So you may have access to that drug or that combination earlier on. As you can see here, that you're still at least receiving the standard of care in that you're not forsaking, you're not saying, okay, well, I'm just really, you know, spinning the roulette wheel. I have nowhere idea how it's gonna land. You're still gonna receive the standard of care. And then, of course, you are contributing to the greater knowledge. It's not that there isn't that benefit. I just wanted to make sure that we weren't necessarily viewing that as the top benefit. On the risk side of things, of course, there are things we still don't fully understand what these drugs, so there are potential side effects. Usually by the time we're giving this to humans, we have a pretty good sense of what side effects we might expect. And so we can discuss that with you. And this all comes down to how important the communication skills, how important the communication is between you and your healthcare team. If there's anything we've proved in oncology, and I teach this to the medical students and the residents all the time, is that having a therapeutic relationship with your healthcare team, much like Theresa was describing when she described shared decision making, that has an impact on your survival. So it's one thing to have the fancy-schmancy drugs, it's another thing to have a good relationship with your healthcare team. If you don't have a good relationship with your healthcare team, you may wanna evaluate that, 'cause it isn't just a convenience, it actually affects your outcomes. You're more willing to share how you really feel about things, what your signs and symptoms are. They're more reactive to it. There's lots of benefits of having that kind of connection. So there are risks, of course, of that. From a financial standpoint, it's never perfect and there's always discussion. Sometimes people see this as a benefit because if they get access to newer drug, then if it's a non-FDA approved drug, ethically, you cannot be charged for it. So the drug is provided free. We are trying to ensure that the process of even receiving that drug or traveling to the clinic, for example, for transportation costs and so on, this is a big issue of disparities in trials that I'll mentioned tomorrow. That in most situations we try to find a way to have that covered as well. But there can be some insurance plans that will have difficulty with certain clinical trials. So that has to be evaluated and looked a little bit more carefully.

- So I'm an introvert, and during the break, and a geek, sitting on the corner and went to clinicaltrial.gov and found out that there are 445 open and recruiting clinical trials that are available. But statistics also shows us, Dr. Joe, that only about 10% of these clinical trials will successfully complete. And so, I guess, the question here is why so little patients participate in clinical trials?

- Yeah, it's a great challenge and part of it is, you know, there are lots of, you know, companies making these drugs and people wanna have their opportunity to see if their intervention works. And so we just expect that not everybody is gonna be successful. But a lot of the things you see on this list have clearly contributed to it. That's one of the reasons why we've spent half an hour doing this with you today, hopefully, to demystify a little bit to help people understand it, 'cause I think people may not be aware, they don't think of it. They think, oh, I'm only gonna think of a clinical trial when I've gone through every other approved therapy. There's a lot of mistrust within the system. The history of research is terrible. I give a lecture to our fellows about the history of research. It's terrible. Within the black community, within the Latino American community, within the white community. I mean, you just go back and look and see what we've historically sadly done. And that's why we have so many rules and protections now. So we have a lot of trust to rebuild. Sometimes patients, they feel like, oh, well, if I go to one of these other larger centers, you know, I'm cheating on my doctor, you know, but I tell you, I've been doing this for years. That's why I often call it an expert opinion, not a second opinion, 'cause second opinion makes it sound like the first opinion was wrong. And I have to tell you, the physicians are very supportive when their own patients get an expert opinion from someone who's truly an expert in the field, because then we work collaboratively together. My phone rings at least two or three times a day from a community oncologist twice already today to a community oncologist asking questions about myeloma. And so building that relationship is important. So having, as Theresa showed on her slide, your community oncologist, but having access and connection to a myeloma specialist, I think, is really important. And then we have responsibility as a medical community to make sure we offer them, that we don't prejudge you and look at you and say, oh, well, they're probably not gonna be interested in a trial. We are very bad at estimating that. That's historically been one of the reasons why we've seen under-representation in trials from African Americans in particular. You know, 20% of myeloma patients in this country are of African descent. Most clinical trials have less than 5% representation of African Americans. And so a lot of it has to do with the way we've couched it and presented it to our patients as well.

- I think you're trying to preempt my question. I'm black, originally from Ethiopia. There are a lot of patients that are Hispanic, member of the LGBTQ community. So they should not participate in clinical trial, right? Because they will be experimented on.

- So the answer, of course, is no, that we want to be as inclusive as possible. If you haven't had a chance to read it, I'm just gonna assume that all of you have read it because I'm sure that you all read the weekly blog that comes out from the IMF. You know, Dr. Durie had a weekly blog for so many years and people were so benefited from it. It was marvelous. I always used to enjoy reading Dr. Durie's. And now, every week, we have somewhat a different person doing it, you know. He's irreplaceable in that way and so, but I wrote last week's blog, or, I guess, two weeks ago now, blog on diversity in clinical trials. So you all read it, right? Remember this means yes. So just pretend, just humor me, just nod and say, oh, yes, it was riveting, Dr. Joe. But in that, I identified a group of us that gathered, we called the Maui Declaration. We were declaring our commitment to diversity in clinical trials by really being thoughtful of the barriers that have historically led to under-representation. Everything from geographical and barriers to the things that I discussed earlier of trust and ensuring that we have greater community engagement and so on. So the whole idea is that everybody should be included in clinical trials. There are some things that may exclude you from a clinical trial that you don't have control over. There are things that we're trying to reduce those numbers. There's some things that may. If you had colon cancer last year along with myeloma, some clinical trials will say, it's hard to know if one thing is influencing the other. I'm just being very open and blunt with you. There's some things that can exclude people from trials. But some of the things that we've historically excluded people from trials, we're trying to reduce, like, white blood cell count, right? So many of us from Mediterranean or African descent have a lower white blood cell count. And it was just always assumed that low white blood cell count means that you're gonna be at high risk of infection. So clinical trials say, well, unless your neutrophil count is over a certain number, there's no way you can go on this trial. Well, you've actually come to now understand the genetic basis of that, something called the Duffy-null status, some of you may or may not be familiar with. And we've learned that people who have that status, who have a lower white count actually have just as good a response to infection as anyone else, even though their white count is lower. So now, we're trying to go back to our clinical trial exclusion criteria and remove that clause that says if your white count is less than one, you can't go onto this trial. Those are the kinds of things that we wanna do, Yelak, to make sure that we're inclusive, that the language is inclusive, that even the booklets reflect the people that are gonna be treated.

- You quick mentioned the importance of having diverse population participating in clinical trials, can you say why?

- Why? For lots of reasons, one, it's not just because we all wanna feel good that everybody's included per se, is that I wanna make sure that I know this drug or this trial, this intervention is applicable to my patient. So I commented briefly earlier, we've noticed, for example, with some of these newer therapies like CAR T-cell therapy, we see some differences in race and ethnicities. The risk of getting cytokine release syndrome that we'll describe a little bit more tomorrow, this reaction that people can get when they get their CAR Ts is actually different by race and ethnicity. We see higher rates of CRS in Hispanic patients when compared to white patients, for example. And so if the whole concept of clinical trial is to prove if a drug is safe and is effective, I wanna make sure I know it's safe and effective to my patient in clinic. And my patient has the right to say, you know, I'm black and this study was done and 99% of people were white. How do we know that this drug can apply to me? So the inclusivity is for the immediate patient to feel to be included, but also to make sure that the purpose of this study, which is to be applied to all myeloma patients, can be done.

- Yeah. While Dr. Joe is finishing, Theresa, Wendy, Robin, you guys can warm up to come up here. Clinical trials are not easy, right? Both for designing, running, participating, there's a lot of logistics and a lot of uncertainty that is involved in there. What are some of the questions patients should ask their doctors? Are they considered participating in a clinical trial?

- Yes. And some of these are listed here and we have resources on the website to help. But the point I really wanna emphasize here is you'll hear about the informed consent, you know, the sort of legal form that you end up having to fill, and these consent forms are getting ridiculous now. Just they're like Warren peace novels. It's a bit ridiculous. No one is gonna read the whole thing. But what's critical is that open, honest communication. Why would I go onto this trial? What am I going to expect with this trial? What are the side effects that I need to be watching for? What implications is this gonna have for me for time? Maybe it's just a pill, but it might involve you going in every day for the first month, or it may involve you only going in once a month. So understanding the logistics of it, doing an quick insurance review to make sure that the burden of insurance is not affected, that it doesn't affect you financially. These are the kinds of things you should be able to ask anything. If there's ever a time to make sure that you're not feeling rushed in the clinic, it's when you're having the Q and A around a clinical trial.

- Prepare your questions. But I think I want to close with this, which is where should you go to find a clinical trial that you are eligible for and that you should consider participating? One of the things that we are doing, I mentioned this at the beginning and I'll mention this again tomorrow, is we are fearlessly collaborating with other organization who can help advance the mission and the vision of the International Myeloma Foundation. One of the things that we are doing is powered by Spark Cure's clinical trial finding engine. We are embedding clinical trial finder within myeloma.org and this will be launched on September 12th, the day our support group leader summit is kicked off in San Antonio. So I wanted to mention that, one, to tell you that we are bringing clinical trial finder on myeloma.org. Two, that we are fearlessly collaborating with others who want to collaborate with us to advance the mission of the International Myeloma Foundation. And three, I wanted to give time to the panel to come and participate in the Q and A sessions that Dr. Joe. So thank you, Dr. Joe.

- If there are no questions, you'll be forced to speak to each other. So I think you may want to have questions, at least for Dr. Joe and some of the other people. All right. I see a hand up on the left here. Michael is coming to you with mic number two. Yeah. There you go.

- [Participant] I'm a little mixed up on something. So I have a three-part question that may help me get unmixed up on something. The first part is, is the standard of care today three drugs together or four drugs together? Do different doctors have a different standard of care? Some doctors believe the standard of care is three drugs together and others believe the standard of care is four drugs together. And some of the doctors, even in the same institutions, believe that the standard of care is three drugs. And other doctors who have spoken here today, I think, who are part of that institution, believe that the standard of care is four drugs. So if you can clarify when doctors think about the standard of care for a patient. I'm newly diagnosed multiple myeloma patient, and I moved from MGUS through smoldering to active standard myeloma in, like, 45 days. So since I'm on a three-drug treatment and my doctor sits on me, that's the standard of care, but now I hear four drugs is a standard of care and I've only was diagnosed within, oh, earlier this month or late last month with active multiple myeloma.

- So first of all, thank you for your question. And thank you for being here, especially this soon into your diagnosis. I hope you're... Oh, thank you. I hope you're feeling the support that you need and getting the information that you need. I'll be more than happy to spend some time with you later on during the break as well. So the word standard of care is challenging because there isn't some perfect ideal, "Everyone is cut with the same cookie cutter," because myeloma is complicated, and myeloma is a little bit different in each patient. When I made reference to the fact that we're sort of moving from three drugs to four drugs or from triplets to quadruplets, we're seeing that in general that four does work better than three. But lots of caveats come with that. Caveat number one, it takes a long time for that transition to happen. So even though a clinical trial shows it, it takes a while for that. Then the company that did it submits it to the FDA, the FDA reviews it, it gets approved. So for example, in patients not going to clinical, not going to stem cell transplant, those four drug trials are under review. They've not been, if you will, approved in that way. So it'd be very fair for someone to say, it's not really the standard of care yet because although the evidence is mounting, it has to go through formal review to ensure that that's a standard of care. What makes it also a little bit complicated here in the US is it's... In a lot of countries, a drug gets approved or not, and it's available or not. Here in the US, it's a little bit different that even before the FDA approves, let's say a four-drug combination, if a group of experts get together and add it to what we call the NCCN or the Cancer Comprehensive Network guidelines, then insurance companies will reimburse it. So we've actually had quadruplets for patients who are eligible for transplant for a couple of years now on the NCCN, but the approval from the FDA was much more recent. So that's a long-winded way of me saying, "It's actually very rational that some would say three is the standard." Others would say, "No, four is becoming the standard." The other caveat that's really important is it's gotta be applied to the individual. I don't just tell every patient's newly diagnosed, as I said before, "You'll take it and you'll like it." Like these are the four drugs and I'm giving them to you. We have to match that to the patient's other medical issues and comorbidities and desires and interests like Teresa shared with us in shared decision making. And some patients may still only get two drugs. Some may get three. Some may get four. So it really depends on the exact scenario. 'Cause it's very hard for us, especially in disease like myeloma, to just say, "Everybody gets exactly this." You know, I'm not trying to make light of it, but it's like asking 10 Michelin-rated chefs, "How do you cook a steak?" You know, and they're gonna have 10 different ways of doing it. There'd be subtle differences. There'd be some central pieces to each of them. And so there is that subjectivity in the treatment. And so that's why it's hard for me to just say, "It's go" or "No go." Lastly, I think the idea of using four drugs in a patient who's not planning to go to transplant is a hot topic. That's why I mentioned it's a hot topic, but it's not really considered the standard of care yet. We still need to learn how to apply it a little bit better. It's more so for those patients who are going to transplant. I hope that answers your question.

- Yeah, since I also have the mic, I want to add a couple of things. One is the need to have a myeloma expert as part of your treatment team, and then choosing the right myeloma expert for you. There are myeloma experts who say, "In our institution, this is how we treat myeloma patients." You want someone, a myeloma expert, in my opinion, who only treats myeloma or they live, breathe myeloma, to be able to be part of your treatment team, if not directing your treatment team. I think the second one is this person, in my opinion, needs to have the clout and needs to be high up in their institution, in some cases, to have the ability to override what others may say, "In our institution, this is what we are doing." In spite of everything that we talked about clinical trials, don't forget that you are an individual and you are unique.

- The only other thing that I would add to that, mainly because you're so recent with your diagnosis and the Isa-VRd combination is not formally FDA approved, this is something that I've seen over the last couple years as we've heard about quad therapies and should we or shouldn't we until the data really came out, is the doctors oftentimes were waiting on some of the blood or the bone marrow results, the FISH studies, and would reserve that quad concept for people who are demonstrating high risk features within the bone marrow test results. And so it may still be a consideration that your doctor is thinking of, and by all means, you should be bringing this conversation to that doctor. But it may be something that's still in the works considering that option based on those FISH results if they haven't come back yet. I'll just throw that little bit in.

- Okay, number two and then number one.

- [Participant] I was wondering what is the difference between a patient that's on their way to a bone marrow transplant and one that's not?

- Yeah, that's a great question. Again, a question that will have multiple answers depending on who's asking it, but... The concept that I shared earlier in the 101 session was that, historically, we've felt that transplant or that big whopping dose of treatment that I described is of benefit to myeloma patients. But we know that it can be really harsh on certain individuals. Historically, we kind of had more of a simple age cutoff, and frankly in most countries in the world, there is an age cutoff and that age is often 65. So in most countries on this planet, if you're 65 or over, you are not eligible for transplant. Period. That's why they do a lot of these clinical trials with patients that are... You know, in the two trials that I mentioned, the IMROZ study and the BENEFIT study where patients were so-called ineligible transplant, those patients were pretty much all between 65 and 79. They had a cutoff of 80. Here in the US, we've been a bit more flexible. We've said, "Look, you know, we have a lot of patients in their mid and late 60s who are still very fit, very active, who could tolerate the procedure. So what differentiates them, this eligibility, is not easily defined, but is a process of evaluating someone as to whether or not they're healthy or fit enough to go through it. Because the process is quite difficult. You know, you become immune compromised for several days. You can get quite sick with it. So in general, if someone is under 65, they're usually eligible. If they're over 75, they're usually not eligible. Where that assessment of someone's fitness becomes really important is between 65 and 75. And again, some centers are very transplant-aggressive, and they want to transplant as many people as they can up to that age or around it. And others are a little bit more, "Hey, we've done really well without transplant in a lot of patients so maybe we don't need it." But that's usually what makes the decision. And it comes back, as we've said so many times today, to a conversation with their doctor, do I want to transplant or maybe do I want to collect my stem cells for transplant and not have it right now and defer it or delay it for later, that's also a third option.

- [Participant] But why would you give the four drugs to someone who is going to transplant and only the three to someone who is not?

- Right, so a great question. So if you didn't hear the question, the question is, why would you then give four drugs to someone who is going transplant and three who's not? It feels like they're getting even less therapy. Historically, those patients not going to transplant, obviously, are older and more frail and we didn't think they could handle three drugs, let alone four. But now as we've come to use these drugs more effectively and more carefully, we've learned that with lower doses, and the right strategies, we can give more to them. So the idea was not to try to deprive those people who are not eligible for transplant but was to make sure that we're not overtreating them. Right, our greatest Adagen medicine is, above all, do no harm. And so I want to be careful. I have a 86-year-old individual who's frail and weak. I'm not gonna give them four different chemotherapies together, that may be very inappropriate to do. So it's a question of matching the treatment to the patient.

- We're treating a person with myeloma, not myeloma, yeah.

- Right, number one.

- [Kent] So Dr. Joe, I'm interested about the community physician component to clinical trials and specifically... I guess, kind of two questions here. The first is how do you find most community physicians are alerted or educated on the ability or eligibility of clinical trials currently? Does it come from pharmaceutical networks? Does it come from things like ASCO or ASH? And then, secondly, how how does the IMF or patients like us become also more engaged with them in terms of, potentially, informing them or educating them about the potential for clinical trials?

- Yeah, I can start, maybe, Yelak, you can wrap up with the second question. So first question was really how do docs know about clinical trials? And you summarized some of them, and I think it really depends regionally where they are is that... In a disease like myeloma where the majority of patients are still treated by a community oncologist who spends the vast majority of their time in solid tumors, they have their go-to person for myeloma, right? So I joked earlier about my phone ringing all the time. I'm the go-to person for a lot of community oncologists in the Phoenix area, and we have a lot of community oncologists there. And so they learn about what's available through their go-to person or their go-to institution. And one of the things we've strongly encouraged, like, for example, my institution, we send out an email every two weeks with a listing of all of our trials in very simple, sort of, digestible bits instead of the whole long description to anyone who's ever referred a patient to us through an email. And so that's how that network grows. We think that's something we can leverage and do even better. And then you're right, when people go to these medical meetings and so on. They're aware of CAR T-cell therapy. So before CAR T-cell therapy got approved or bispecific antibodies got approved, they were aware that those modalities were under investigation, and were under clinical trial. And so now, we're telling them, "Look, we have a whole new wave of bispecifics and a whole new wave of CAR T's that are being developed. These patients can come on those trials as well." In terms of the IMFs approach to it, I'll let Yelak answer even a little bit more, but I think our audience, says the IMF, has historically been a patient population and a myeloma doctor population as well as our advanced care providers, and particularly, through the Nurse Leadership Board. I really see us moving in a direction where we're, in addition to that, really trying to be a stronger voice to the general oncology community. Because myeloma's become so complicated, because there's so much that a community oncologist who treats breasts, colon, lung, you know, I mean, they treat 40 tumor types, they can't keep up on anything, we want to be a greater resource to them. And even things like the SparkCures program that Yelak is describing, I think, will be a great resource to them.

- Yeah, absolutely, Dr. Joe. I think there are two aspects of your question as well, Kent. One is how do the community physician know about it and send their patients to a clinical trial or refer them to a clinical trial? But don't forget, there's also a fear of losing the patient to a center of excellence if that patient is referred and doesn't come back. So I think there needs to be some level of trust that is established between the community physicians and the centers of excellences where if I refer you for CAR T or BCMA therapy to the centers of excellences, you'll get your first few doses and you'll come for your maintenance dose or whatever it is in your community physician. So I think there are opportunities for us to educate and also advocate on behalf of myeloma patients and on behalf of whoever is doing reimbursements for these community physicians as well. So there is the bottoms up, educating the patients so they can actually advocate for themselves and go to the doctor and say, "These are the clinical trials that I want to participate in." There is the angle of us empowering the community physicians and the patients through a digital technology and allowing them to bring that knowledge to the community physician, but there's also that additional level of trust that needs to be established between the community physician and the centers of excellences.

- And I would just add to that the role of the patient advocate in things like ECOG and NCI and these places where the clinical trials are being developed, we need to make change in what those concepts and protocols become so that we can start a therapy at an academic center and transition into the community so that there can be a seamless, you know, stream of care and still allow people to participate in clinical trials. So the role of advocacy is really big in this particular topic.

- Yeah, number two over there.

- [Participant] Hi, Dr. Joe. I have a couple questions about the understanding of the labs. So my husband's been diagnosed seven years ago and we've been doing all the standard, you know, IgG, IgA lambda-kappa ratio and so on so forth. And then recently, he started on Tecvayli, and all of a sudden, his kappa and lambda says they're undetectable. So like, at some point, it just goes away and it's no longer a marker or how does that work? 'Cause when I saw it undetectable, I was alarmed, but the doctor doesn't seem to care. And the other question about the bone marrow autopsy, is there a rule of how often that needs to happen? It only happened once at the very diagnosis for us, but the way you were talking about it, it seemed like it's something that happens somewhat regularly.

- So two great questions, and I'll be brief in my answer 'cause I know time's going quickly. So one, we are learning with a lot of our newer treatments now that the normal levels of our regular immunoglobulins... So we all have some of the IgG, the IgA, IgM, as you mentioned, and we all have some of those light chains, right, that Teresa and I showed on that original picture. So whether you're here and you have myeloma or not, we all have some that should be circulating our body. When we treat myeloma, often, we try to get rid of the bad ones, but there's some friendly fire and we hit good ones too. We sometimes call that hypogammaglobulinemia or people get a low immunoglobulin level. Some of you have already talked to me at the break. I know some of you are getting replacement immunoglobulin, what we call IVIG, or intravenous immunoglobulin, because you're higher risk of infection by not having that. Some of these new therapies that we're using are particularly powerful in that. That's why I started the hot topic where the third hot topic was less is more 'cause I think we're actually probably overtreating some of these patients. And what's happening, like you described with your husband, where that kappa and the lambda level disappears, that could be too low, 'cause that may be reflective of his immune system. But I don't think it's 'cause your doctor doesn't care. They're happy that it's not high, right? 'Cause it's telling us that, "Okay, maybe we've wiped out some of the good, but it also means we've wiped out the bad." So that's something we need to monitor. Your second question was bone marrows, how frequently? I'm not a big fan of putting a needle in someone's butt unless they need it, right? I'm just being, you know, very blunt here with you that there isn't a strategy where we say, "Everyone needs a bone marrow every year or every two years." Sometimes, in certain protocols or institutions where they're collecting information, they do it more regularly. But typically, we do the bone marrow test to originally make the diagnosis. If someone has a bone marrow transplant or a stem cell transplant, we typically do one somewhere around day 100 afterwards as sort of a convention to see what the marrow's like after a transplant. And then we may consider doing a marrow at any point when someone relapses because people can go from standard risk to high risk myeloma, and the only way we can know that is by doing the cytogenetics. And the only way we can do cytogenetics is by doing a marrow. So it's not something we may do as regularly as blood tests or even as scans, but we don't have a formal, you know, "Thou shall have a marrow every year, every two year" concept.

- [Moderator] Sorry, okay.

- [Participant] My question is about two steroids, at least, I think, the second one is a steroid. So I've been on Velcade for seven months and a very low dose, like, one...

- Sorry, can you move the mic right to your mouth? It's hard to hear you, I'm sorry.

- [Participant] Okay, I've been on Velcade for seven months, just one... How is it measured? Milligram, 1 milligram. And right away, I developed styes, styes that don't dissipate. They don't go away. They get better, but they stay on my eyes. With the first one, my doctor prescribed an antibiotic. Didn't seem to help, and I can't live on antibiotics. So it's worrisome for me. And now, I'm going to be getting maintenance on Monday. And instead of 1 milligram, he's going to up it to 1.3. So I'm concerned about styes. I'm wondering, why you think people developed styes when they're on Velcade and some don't? I don't think it's because my immune system is low, because it's not, but they're just there. And I mean, it interferes with the... You know, the eyelashes are missing permanently. So that's my first question about Velcade. And then, I'm going to start Medrol every other day starting this Monday, and I'm worried about that also because friends have told me that you can develop the moon face. And I'm wondering what your thoughts are on those two drugs and why?

- You wanna start, Teresa?

- Yeah, Well, it...

- The styes and...

- With the styes, you know... First of all, we know that with some of the newer therapies, like the Belamaf, or Belantamab mafodotin, that people have experienced ocular toxicity and we're aware of that, but it's not very common with Velcade. Actually, I've only heard of it a couple of times with Velcade, but there can be some infection, irritation of the eyelid, and you know, sort of makeup related, making sure you're getting rid of all old makeup and putting on new, maybe taking a holiday from it. But my first question, I guess, would be, you know, has an ophthalmologist been involved or a dermatologist been involved to really take a look at what might be the true source? Is it truly Velcade? Or is it infection based?

- Yeah. I think the other thing I might add to that is...

- Yeah.

- I've had a few patients in my practice... If you're getting styes... And again, you know, the caveat always is we're not... I mean, I am a medical professional, but I'm not sort of serving in that role here. You know, obviously, discussion to have with your physician. It's hard to be very specific, but I have had about half a dozen patients over my career who just have recurrent serious styes with Velcade exactly what you're describing. And honestly, the only way to stop it is to switch from Velcade to something else. The mechanism is not fully understood, and I think it's a good idea, get derma holiday. I mean dermatology involved. I like teasing my colleagues, you know, to have a look. You know, again, I'm not trying to make light of it, but, you know, they have some idea... There's some, you know, symptomatic things that they can do. But ultimately, if they keep coming back, in my experience in the few patients I've had, but I've discussed this with lots of other doctors 'cause this comes up about once every 20 patient-family seminars, the only way to really get rid of it is to stop, unfortunately. So typically, we'd have to look at what other options there may be if it's affecting your lifestyle as much as it sounds like it is. Because as Teresa said, I don't treat myeloma, we treat people. So we have to be really careful with that. I assume that they're talking about Solu-Medrol, like on a steroid, that they're gonna give you every other day. And there's different strategies for steroids. Typically, we've talked about dexamethasone so far, which is typically a once-weekly thing. 'Cause if we think of dexamethasone being so-called a pulse, it's kind of like a really slap in the face of myeloma once a week. Sometimes, that dex, so that steroid, is too much for people, and we've historically gone to a much lower dose and give it every other day. Maybe you and I could chat after a little bit more about that because, you know, I don't wanna question someone from the stage, but that's not a strategy we typically use a lot in maintenance anymore to continue steroids. If anything, we tend to want to not give steroids. I have seen steroids themselves, by the way, cause styes. So I may want to minimize steroids in your situation, but maybe we could discuss a little bit more at the break.

- All right.

- One more question.

- Yeah, we can take two more questions if there's more question over there.

- [Participant] Why do they wait...

- [Moderator] I got you. You wanna use the mic?

- [Participant] I can yell pretty good, but why do they wait until you took some fairly dramatic drugs to collect your stem cells? Why not get 'em before that? I just doesn't... I'm just curious.

- Sorry. Did you ask why do we give that induction treatment before collecting the stem cells?

- Sure, yeah.

- As opposed to just collecting 'em off the start.

- Good.

- Right, great question. So the reality is these stem cells in your marrow are surrounded by myeloma. And we have tried exactly that thing. It is very hard to collect good stem cells when someone has a marrow full of myeloma, even if it's not full full, like 10, 20, 30%. You know, the thing with myeloma that is weird is that you don't go to another patient and say, "Well, how many plasma cells did you have in your bone marrow?" And I'm like, "I had 20%, and I heard he had 40%." You know, again, I'm not trying to make light of it, but that absolute percentage doesn't mean that 40% is twice as bad as 20%. Myeloma is evil and even small percentage of it can really invade and overtake the bone marrow. So it is not gonna let those stem cells get out easily. So that's why we've learned that the collecting of stem cells, let alone the benefit of transplant, is had when someone's disease has dropped at least by 50%, if not 90%.

- One more question.

- [Participant] Hi, what is your opinion of the new Pemgarda, especially because the new COVID vaccine is not available. I know it's not readily available at all centers, but would that be something that you recommend?

- Does anybody else wanna take that? I feel like I'm taking every question here.

- No, I don't wanna take that one. I just, again...

- Yeah, I think it's just a little bit early yet. Like it's... So let me back up for just a minute. Because we're trying always try to find this balance and you probably saw from our blog last week, you know, that COVID, there's been a bit of summer surge in certain places. We don't wanna make it sound that myeloma patients are so at risk of COVID or other, you know, community acquired infections, that you're gonna get it tomorrow by noon and you're gonna be sick and be horribly sick with it. On the other hand, we also want to encourage people that vaccinations have clearly demonstrated tremendous benefit in all patients. Cancer, non-cancer, cancer on therapy, not on therapy. I mean, it's very, very clear that there are benefits. Obviously, it has to be discussed individually. There are a whole series of products now that are being developed to help protect people either because they can't get a vaccination or it's anticipated that they're not going to have as robust a response to vaccination. The reality is we just don't have a lot of evidence for it, right? I've always tried to think of whether it's COVID or any of these infections. I mean, long before anybody got excited about masks... You know, we were talking about masks after transplant... For those of you who've had a transplant before COVID, you're familiar with this, right? We had the whole discussion about the hand washing, social distancing, hand sanitizer, masks. Those weren't new when COVID happened. We had been doing those. And I try to think of it as sort of a multi-hit phenomenon that we want as many layers of protection as possible when we're at greatest risk. So I think I would stay tuned to the IMF website because we do try and comment on these things. I think the evidence is emerging. I think, in short, I would encourage people to keep up with their vaccinations, to talk to their both oncologists and their primary care, 'cause sometimes, we as oncologists think that the primary care is taking care of it, the primary care thinks that we're taking care of it, so that the ball can get dropped. And to just to keep up on, you know... The FDA actually has been quite good, and the CDC and their guidelines on the websites, that's how most of us have kept informed.

- So we'll have more panel questions tomorrow. I want to say two things before I invite Robin to close us for this afternoon. Daniel, Robin, Dr. Joe, Teresa, Wendy, thank you for your presentation and being on the panel. And I also want to tell you that whether you are here... After a couple of months of your diagnosis, you are here because you have a broken back. You are here having supported IMF for many years after losing your loved ones. Or you are really doing well and thriving with myeloma, thank you for being here. And welcome, again, to the Los Angeles Patient and Family Seminar.

- Robin mentioned that when I was asked how I want my title to be, I said, "A 28 year myeloma patient," it used to say, or the suggestion was a 28 year myeloma survivor. For me patient much more than survivor indicates the journey that myeloma patients actually goes through. We are always waiting for the other shoe to drop regardless of we are in remission or in extended treatment holiday or we are inactive treatment. So for me over the last 28 years, it really describes being a patient better than being a survivor. I do understand the dictionary definition of a survivor is, and or survival actually starts the minute you are diagnosed. But this is how I internalize the fight, the dance, the journey that we, myeloma patients make. So having said that, I stand here before you as president and CEO of the International Myeloma Foundation. For those of you who haven't been around IMF for a long period of time, next year we'll celebrate our 35th anniversary since we were founded. So we, hands for us. So the IMF was founded by three visionary people. Brian Novis was a myeloma patient at age 37 and he died before he turned 40. Susie Durie, who was his wife at that time, and they found Brian Durie not in the US actually outside of the US 'cause they even at that time understood that myeloma doesn't have border, myeloma treatment, should not have border and myeloma expertise really can and should come from around the globe. So the IMF will always be grateful for the three founder visionaries and what they have done for the IMF for me personally and for thousands of patients around the world.

So I mentioned to you that I am a myeloma patient. I was diagnosed in 1995, 3 months before my 26th birthday and told I will be dead before I turned 30. And the doctor called me at the place where I were doing internship and he said, "Hey Yelak, you have multiple myeloma. It is not curable but come to my office and we'll figure out what the treatment options for you are." He never said cancer. So the approach I came up with at that time was he don't say cancer, he don't say, he said, you'll die. But he really didn't indicate he knew when. So I said I'm going to fight this as much as I can. And at that time the drug of choice that was available, some of you here know what is, that is VAD, Vincristine, Doxorubicin and Dex. So you guys complain about being in the hospital for three, four hours when you are getting your daratumumab infusion. This was a 72 hour infusion that lasted days. The advancement when I got myeloma was that instead of being in the hospital, they actually gave you a pump you carried and you carried them pump for three days plus wherever you went in the bathroom, in the shower, in school work or whatever it is that you want to do. That is actually me. I actually crop that picture because I was showing too much leg. But that thing you see in the bag is actually all of the medicines that I needed to carry for the three, four days that I was on treatment. And this is really a life as many of you know, giving blood, waiting for your blood work to come back, deciding what to do next, finding your myeloma expert and having them explain what you have just heard from your MyChart results has been really the journey that I have traveled and I'm sure many of you have traveled. And one of the number one questions I get actually is, oh, you are a 28 year survivor because you haven't been on treatment the first few years or you were diagnosed as an MGUS. You'll have this as part of the QR code. The rate items on that are all the treatments that I have been on.

So I have been on many drugs, have had at least five remissions and relapses and I think I have chosen to get up whenever I relapse it. I have chosen to celebrate whenever I achieved however long that remission is. And I have really chosen to educate myself, connect with others and build the relationships I need in order to be able to navigate my myeloma journey. But as I mentioned to you at IMF, it's not just about me. Sometimes it is but not always about me. It is also about the patients that touch us and we serve. This is Ponima, she lives in the Bay Area. She was diagnosed with multiple myeloma in 2021 at age 39. And she had those things are not really pumpkins, those are her twin daughter and son that were 1-year-old at that time. And her thought process was, I have myeloma, it is incurable, it is cancer, I'm going to die of it. Do I have three months? Do I have one year? Do I have five years? So life, as she said, it was very turbulent during those times. This is actually her right after she got her stem cell transplant and really went back away from her family for a period of time to recover in that 90 day quarantine, this is her during that time. During her diagnosis, she also had a lot of soft questions, right? What treatment should I be on? What help is available for my physician, for my family, financial and emotional? What are, who are this she called it, she called us unicorn patients that have survived 10, 15, 20 and in some cases 30 years. So she was able to find me and she and I had a conversation and we kept in touch throughout the her myeloma journey and this is her now. She has really been, she had founded a genomics company and she has been promoted from just being a CEO to a president. And she was invited and gladly joined the board of directors of the International Myeloma Foundation.

So I tell you that to tell you also that myeloma is and can be relentless opponent in your myeloma journey. Once you have myeloma, however long is your remission. I recently heard of a patient who has gone through a stem cell transplant and has been of all treatments for over 20 years. And I hear there are many of them like that. But all of these patients, whether you are in treatment or in remission, you are actually waiting for the next shoes to drop. And we all of us leave blood test to blood test, whether that is monthly, quarterly, every six months or on a yearly basis. So our goal at the International Myeloma Foundation has always been to empower patients with myeloma and their loved ones to live a full life. But our promise has been and will continue to be, we will fight alongside you every state of the way. So the way I describe the International Myeloma Foundation is this way, right? The mission of improving the quality of life of myeloma patients while working towards prevention and the cure has been our founding mission. And not only were we interested in finding the cure and preventing myeloma, we were also really interested in ensuring that myeloma patients have a full life and a high quality of life. The vision that we have articulated and started speaking towards is a world where every myeloma patient can live life to the fullest unburdened by the disease. We understand that as a myeloma patient you'll have ups and downs, but our goal is to make sure that each one of you, your loved ones caregivers, your family member is able to live a full life. Whether a full life is jumping off the airplane for you or a full life is being able to take a walk from here to your home. So those are really our now vision and mission and they are all boldly, in my opinion, formed on our four founding pillars of support, education, advocacy, and research.

That is why that the IMF has been holistic organization, an organization that has really been able to then go up and down with the times as needed because we have four solid founding pillars of support, education and advocacy and research. And we are able to support the family, the patient, and the other doctors around the US and in the world to be able to meet patients wherever they are. When I came to the IMF, one of the things we said was we need a multi-year strategy on how to move the IMF forward and meet the challenge of today but also be prepared for the challenge of tomorrow. Over time, instead of making those strategy outcomes, we decided to make them guiding principles. How is IMF going to meet those challenges? How are our programs to continue to thrive and evolve in order to meet those challenges? And we came up with input from you patients, key opinion leaders, pharma companies, and many other people that are within the IMF ecosystem. We have three guiding principles. Number one is raising the bar. Every program that we have done, we are doing and we'll be doing. We will understand its impact, we'll measure its reach and make sure that it is driven with input from each one of you as we move forward. So when you give us feedback today and your feedback from tomorrow, it just doesn't come to me. It doesn't go to the shredder. It actually goes to informing us how we can improve our programs as we move forward. And that this patient and family seminar was tweaked if you would. We had a really good patient and family seminar in the past, but we feel like this one is a step above that because we have collected feedback literally from 1500 patients and family members who have attended our seminars over the previous 18 months. And that is what we use to inform how we will we tweak the programs here today. So our goal will continue to be to listen to your voice, adjust our programs and meet you and the challenge of today, wherever we need to adjust as an organization.

The second one is broadening our reach. The IMF reached thousands of patients, thousands of key opinion leaders and myeloma specialists from around the world. But we still believe that we are not reaching all those who we need to reach in order to really bend this curve and flatten it. And I don't mean kill it, it's actually make sure that everybody is living their full life. So one of the things that we are advocating for is can we reach 90% of the myeloma patients that are diagnosed with myeloma within 90 days of their diagnosis and ensure that they have the information they need, they have the resources they need in order to be able to battle myeloma for the rest of their lives. This could be connecting them with key opinion leaders. This could be providing them expert opinion. This could be helping them navigate their resources or this could be actually telling them that doctor you see over there, Dr. Joe, you may not want to to be with him, find another doctor. You know, maybe go to Emory or something like that, right? We want to be able to say that. The last one is we really want to be able to innovate every step of the way.

We see Amazon, we see Netflix and other what I call for-profit organizations significantly taking advantage of today's technology in order to personalize and customize services to the population they serve. Why can't we use those same technologies, those same advances in data and analytics in order for us to be able to provide a more personalized experience for you? And I chose the word experience intentionally. We don't want to have a transactional relationship with you. We don't want Eric to come get something from IMF website, come to the patient and family seminar and then we don't see him until the next time when he needs us or when we need him. I really want to make sure that we are transforming our interaction with you from being transactional to experiential. We want to improve your experience of having to live with myeloma. Whether you are a newly diagnosed patient here with a broken back or someone who have gone through a transplant and because you are double hit myeloma, you haven't, that transplant hasn't really worked for you. We want to make sure that we provide you the experience you need and you want and you deserve in order to live a full life with myeloma. So one of the questions I keep on asking myself and getting feedback from others is not how we become a superpower, but understanding what is IMF's superpower today that we should be leveraging and amplifying as we continue to move forward with our research and support education and advocacy strategies. So the four pillars are this, and I won't read all of the programs here, but one of the things that I'm really proud of because I grew up in that system is the IMF support groups.

We have over 150 of them in the US, I was a part of the North Texas Myeloma support group, the best ever support group, right? No, okay. Then I moved to Arkansas for work. There was no support group. I felt alone and like I felt like I was really living myeloma by myself, although I have had all of the supports that I had. So I ended up forming a support group in the northwest Arkansas area and I said, uh-uh, I'm not going to navigate this journey by myself. So I tell you to tell you that you don't have to navigate your myeloma journey by yourself. You don't have to recreate the playbook. You can actually have others help you. But be open to that help as needed. We also have an info line. Missy is somewhere in the back, Theresa, she mentioned that yesterday. She's here in the front. We also not want to just engage with you here and be done. We don't want to just engage with you on social media on our website and be done. We really want to make sure that if you need, you have the ability to call someone who's able to answer your question. Do we need to expand our info line? Probably. Do we need to provide more service through our info line? Probably. But it is really one of our signature offerings that we have had for the last 25 years plus. The other one as it comes to research is the research you may have heard from the International Myeloma Working Group or IMWG, that is a collection of over 320 key opinion leaders from around the world that come together and decide what are the unmet needs? How do we move the guidelines of treatment forward and how do we engage and interact with the food and drug administration for drug approvals and providing treatment outlines.

And these are key opinion leaders today from 41 different countries and over the last 15 years have published over 62 papers that have been published in the major journals. And today actually the Food and Drug Administration, the European Medical Association, use some of these guidelines as it relates to treatment, treatment outcomes and things like that. So this is really one of our key superpowers that we have is being able to convene various key opinion leaders in spite of them, making fun of them working at Mayo or Emory or TGen. They are choosing to work with each other in order to advance science on behalf of myeloma patients. So these key opinion leaders work from MGUS all the way to relapsed refractory multiple myeloma and anything in between. So that you say, okay, your focus is on research only. No, we do the same thing as Daniel showed you yesterday. On advocacy side, we advocate for access, we want to eliminate financial barriers and we want to secure fundings for research by working with others in the same space. MMR, FLLS and others. Yes, I call their name because we are wanting to collaborate on behalf of you. And when I say sometimes at IMF is about me, not me as president and CEO, but me putting on my patient hat, I want to make sure that we advocate for that. But the question I have been asking myself and others and key leaders within the IMF and outside of the IMF is, is everything we do enough? Are we doing enough? Initially I started answering it no, but no meant like what we did we should not have done, right? But so I have tweaked it based on feedback from people. It is now, yes, but we are doing a lot, but we need to do more. And the question then is where should we be doubling down on our effort and resources as we move forward? And these are five areas. This is not a timeline.

These are all the things that we'll be doing at the same time as we move forward. Number one is, can we ensure that you are diagnosed on a timely manner? I don't want to necessarily say early diagnosis is good, but are you diagnosed in a timely manner? If you talk to Richard back there, he'll tell you that he was a day away from his kidneys shutting down and being able to not get off apheresis for the rest of his life. And he was two days away from actually completely dying of multiple myeloma that was undiagnosed. There are many stories like that in the patient population that I can tell you that if they were diagnosed timely manner, their outcome could have actually been much, much better. So that's number one. The second one is if you are diagnosed with myeloma in a timely manner, you should also have access to good quality care. And we are working through coalitions, through our support, education, advocacy and research arms in order to ensure that patients have the access they need to good quality care. But the other item that's related to that is also being able for you to have access to novel therapies by specifics, CAR Ts and anything else that may be coming down the line. We want to make sure that you have access to that. What does that mean? It means that not only will we be advocating for those drugs to be accessible, but we will also make sure that we advocate for you to participate in clinical trials to bring those drugs into market. That's why Dr. Joe and I yesterday focused for 30 minutes what it takes to actually go through a clinical trial. The fourth one is we need to ensure that we do research that matters. In the slide I showed you during my diagnosis, the first 40 years from the '50s into the '90s, there was two approved drugs. All of them in the treatment of myeloma as it relates to high dose chemotherapy.

From 2000 and to today, over the last 20 years, there are 17 brand new drugs that have been approved for the treatment of multiple myeloma. But we believe that that's not enough. We at IMF in collaboration with others want to make sure that research that matters most to the patients is done, research that matters most to drug approvals is done and we want to continue to bend the curve so myeloma becomes curable. The last item is a strategy collaboration. We'll collaborate with whoever wants to collaborate with us in order to move the needle forward for multiple myeloma. And so, how do we translate those five items into a strategic priority for multiple for us, for the International Myeloma Foundation. Number one is, is I told you when I spoke of our info line, we are doing a lot of work there, but we can do more. So leveraging our unparalleled access to the myeloma patient population, key opinion leaders, our relationship to industry payers and others. We want to stand concierge service for myeloma patients. I can't call any myeloma doctor in the world, not because I'm a myeloma president and CEO of IMF, but because over the years I have been able to build the relationships through the various work I have to get me into something. How can we ensure that same level of access that I have actually is democratized, if you allow me to use that word. But we also understand that 60 plus percent of myeloma patients get diagnosed and get treated in the community physicians hospital. So we need to also provide lifeline to the community physicians to understand when Todd is sitting in front of them, what treatment has he been on and what treatment is recommended for Todd.

So that is really the concierge service we want to bring in, in order for us to be able to reduce the time to hope. The second one is the craziness today is related to real world evidence. We want to use not only clinical trial data and or sanitize data like that, but input from you and your experiences in order for us to be able to inform research and policy as we move forward. And the last item is Dr. Joe says the question is the answer. What is the question that really needs to be answered in order for us to make meaningful progress towards finding this cure? Ensuring that we don't have to hopefully someday take decks and really be able to live a full life. And we believe that we have initiated that thought process through our scientific advisory board. Which brings me to this almost last slide, which is we are not only the industry, not only the landscape and the ecosystem is going through a transformation. We are going through a transformation as well as IMF, right? For the first time in our 34-year history, we have a non-founder, President and CEO and we have a non-founder board chair. Our guiding principle will still be you, the patient.

We will still be patient centered and will advance the need of the patient. But we have gone through a transformation, and we will continue to go through a transformation in order for us to meet the challenges of tomorrow. We have significantly new board members that have really helped challenge our thinking and have, some of them are I think in this room, maybe, have become my bosses that are holding me extremely accountable not only to what we say but also to the patient population. And then the last one is ensuring that we do research that is meaningful through the scientific advisory board. And one of the speakers today is a member of the IMF Scientific Advisory Board. And we are very bullish where we want to go using that. But I want to conclude this with this, what did I say yesterday? My motto is to live as long as possible with utmost quality of love possible, understanding myeloma is not yet curable. But one thing I want to continue to remind you and you should not forget, is while avoiding to die, don't forget to leave. So that is my last slide and before I turn it over to Dr. Joe, I want to show you this and then I'll let Dr. Joe come.

- So I'm gonna ask you Sagar some questions over the next little bit trying to peer into the future. And maybe I'll, I'll let you just sort of kick off. If you were to be prophet Sagar for the next couple of minutes, can you predict two or three major things that will change significantly in the lives of myeloma patients or in the myeloma community in general as to what we're gonna be either treating or diagnosing or how myeloma is gonna change radically over the next few years?

- Alright, well thank you and thank you all for being here today. So I'm gonna start off, I'm gonna avoid the question. I'm gonna pretend-

- Yeah, well see. You know, he's a leader in management, he knows how to avoid the question.

- I'm gonna come to the question, first, but I do wanna address one thing that Yelak said, which is sometimes we poke fun at each other in our different centers. And quite honestly, we do that only out of a sense of camaraderie. Nobody I think in our field believes that anybody has the answer. I think we all believe that there are multiple paths up the mountain to try and cure this disease. And we may have our preferences, we may have our biases, and we poke each other 'cause we know each other and we enjoy each other's company. And that's one of the things that I think really makes the myeloma community so unique. If you go to other diseases in cancer, you don't see that level of camaraderie. You wouldn't see the IMWG output that Yelak put up there. If every disease, it wouldn't be unique for us. Every disease doesn't have that sense of collaboration and partnership that I think we have. And I consider myself very fortunate to be a part of that team, 'cause it is a lot of fun. It's a lot of fun for all of us to get together and just brainstorm. So I'm gonna get-

- I'll pay you later for that comment. That was fantastic. You know, it was really well done. But it is true. I just wanna emphasize that we've often had people from other diseases say, you know, we need a version of the IM, we need the leukemia version, or the prostate cancer version of the IMWG.

- Well, I'd say good luck to them. But anyway, so I think, when I think about what does the horizon look like? The first thing to say, again, getting back to that kind of competitive spirit that we all have is I'm right. And nobody can tell me I'm wrong because nobody knows the answer. And so I think the first thing I'd say is, I think we're gonna get to limited duration therapy. And what I mean by that is, most of us now, if people are responding to treatment, we'll continue on that treatment until either toxicity or it no longer works. And I talked to somebody earlier today about being on Revlimid for 25 years, or 26 years, or however long it's been. That is the norm right now. But I think that the new classes of drugs we have are more effective at eliminating the clone as opposed to just controlling the clone. And that will be one revolution that I think we'll see. The second thing that I think we'll see, and then I'll stop.

- Yep, no, it's fine.

- The second thing that I think we'll see is understanding how precursor disorders can predict for higher risk of developing myeloma. And we know that MGUS is an age related phenomena and that it goes up as patients age, but I think we're gonna get better at understanding which MGUS and which smoldering patients we should intervene early on and which ones we shouldn't, and potentially prevent patients from ever developing symptomatic myeloma. Those are things that I think we're gonna be doing in the next five years.

- Fantastic, well, let's drill down on those two and then I've got a couple other questions for you. So, coming to the stopping of therapy and I can't imagine that any patient in this room is going to disagree with that concept, right? How many people here want to stop therapy? All in favor, sit down. Right, okay, good. So like, you're all with me except one person who stood up, right? As I said that, there's always one in the crowd. No, but help me understand that a little bit more. 'Cause right now, you know, we do have these glimmers of light. Like when patients get a CAR T-cell therapy in general, it's a one and done approach. We treat and we stop. We don't typically put people on treatment after CAR T, but for things like maintenance therapy, you know, historically we've just said, you'll take it. Not very many people get to over 20 years of Revlimid. But most people will go on for long periods of time. How do you think that's gonna happen? Is that just gonna be because we're gonna develop different drugs and sort of the next gen? I know you've been a big part of the next generation of Revlimid drugs, the cell mods and things like that. Or is it going to be that we're going to have tools that can say, you know, you're the person that we can stop right now instead of giving you Revlimid forever?

- Yeah, no, I think that's a great question and I'm gonna undermine your first premise, with CAR T, is one and done because we actually, at my center, I give maintenance therapy post CAR for the first six months. And I don't do it for the same reason that we traditionally give maintenance, which is we think there's something there and we're trying to treat it. I do it to try and wake up the T-cells. So I think the biology of why we give therapy is gonna change a little bit. When we give Revlimid now until progression, it's because we know that there's something hiding somewhere and that the Revlimid can suppress it, but may not eliminate it. In the CAR T setup, we know that patients can achieve MRD negativity and patients that achieve MD negativity can have really long remissions, but even patients that are MRD at 10 to the minus six still have relapses. And so we've not eliminated the clone. And so what I think we're gonna do, and again, this is the crystal ball, is I think we're gonna use CARs to get to debulk, if you will, to get to really low levels of disease and then come in with something a bispecific on a different target for a limited duration to try and eliminate the escape mechanisms of relapse and then stop. So that's a totally different paradigm than what we currently think about, which is something works, let's just keep doing it until it doesn't work anymore. Now I think we're gonna build on what we're doing to try and get better outcomes.

- So that kind of fits actually for those of you here yesterday with part of the discussion we had around this notion that you know, coming at myeloma in different ways has led to such better outcomes. That's why we've gone from doublets, to triplets, to quadruplets, you know, that it even in lower doses of those different drugs coming at it in a different way. So what you're seeing is that we could come up with some kind of strategy that says, okay, we're gonna reduce the bulk of your myeloma with a certain strategy and then come a different way to get the rest of it. Sort of the analogy I sometimes give to patients says, we really want to clean your kitchen floor, so we're gonna sweep it first. That gets a lot of the dirt away, but then there's still something else. So now we need to mop. And so we get the mop, but then we need the scrub brush in the corner. So if we can predictably use the broom, the mop, the scrub brush in an order, then we can say we can stop scrubbing.

- Yeah.

- Instead of just constantly sweeping all day long because dust is re-accumulating.

- No, I think that's-

- Okay with you?

- That's a great analogy. And the way that I think about it in practice is, many of you know, BCMA is a target for many CAR T, the two CAR T cells we have approved. When patients are progressing after a BCMA CAR, those myeloma cells don't always express BCMA, or their BCMA low, meaning that if all you did was just keep giving more BCMA directed therapy, you're not gonna get anywhere because those cells have already figured out how to get around it. So what you and I are talking about is you give a BCMA CAR and then you come on the backend with something that targets GPRZ-5D or FCRH-5, because that receptor is still there, it hasn't been messed with yet. And that's your opportunity to really try and scrub and sweep and mop sequentially.

- Excellent, okay, well I think we got something with this mopping business, right? So hopefully most of you, you're here yesterday when I showed that picture of the myeloma cell with all those things that stick out of it, just to make sure we're clear, that BCMA or B-Cell Maturation Antigen was one of those targets. But we had those other two targets that Dr. Lonial just referenced. GPRC-5D and FCRH5. The other thing I wanna drill down on a little bit with you in this vein, because it's a hot topic. I had two patients even already come to me and say, "When are you gonna talk more about this MRD business?" So very quickly we use these phrases, you know, as I mentioned yesterday, we love to use words that patients don't understand. The second thing we love to do is create acronyms that people can never remember, right? So the acronym of MRD, or Minimal Residual Disease, sometimes it's referred to as measured or measurable residual disease. It just is this notion that we can test for tiny amounts left of multiple myeloma. And it's not something we did historically, because for the vast majority of patients, we didn't fully debulk their multiple myeloma. So you may remember yesterday I commented that whatever measure someone has of their myeloma, their M-spike, their light chain level. I remember myeloma's a crime scene as I said yesterday that it's rare that one a piece of information tells you the whole story. You need to look at the whole picture. But when that gets cut down by half, we call that partial response or PR. When it gets cut down by 90%,, we call it very good partial response or VGPR. When it gets cut down-

- And our lymphoma colleagues always say, "Well what about the NBPR?" The not so bad partial response.

- The not so bad partial patients Exactly, I thought they were asking about NPR. But anyway, so, and then when we get to a 100%, we call it complete remission, but what we call it a 100% complete remission, we know just as Dr. Lonial said, there's still some disease left, right? If you look at the floor here at the Hilton, no disrespect to my homies here at the Hilton, it looks really clean, doesn't it? But I guarantee you there's some dirt there, right? If I get a wet Q-tip, I'm gonna go down and show you that there's still a little bit of dust in those carpet fibers. MRD or minimal residual disease is testing for that tiny little bit of dust. And even with MRD, we have different layers of depth. Dr. Lonial mentioned that we had a 10 to the minus five, 10 to the minus six. Those are just cutoffs of how many myeloma cells we can find in a certain number of other cells. So we look for one myeloma cell in 10 million or a hundred million cells. So that's a tiny, tiny amount of dust in the carpet. But we know that although it may be a tiny amount, it could still grow back and be a problem later. So my question for you then Saga is now that we're doing more of this MRD testing, and we don't necessarily have to get into the details of how we do it 'cause there are different methods and so on. But what does a patient, what should a patient now know about MRD and secondly on the theme of the future of myeloma, do you think MRD is going to play a greater role in the way we decide on stopping therapy like you said before or completely switching gears with therapy? Is it gonna be something, is it gonna be a tool that's gonna guide us a lot more in the future? And obviously I'm leading the witness your Honor, because I'm assuming that you're gonna say it's going to be more used in the future.

- Yeah I think it will. But I think we have to understand the nuances of what the test means and how often to get it, and what an individual patient's myeloma tells us. So every patient that's MRD positive that was MRD negative doesn't necessarily need to change treatment. And in fact, I would argue most patients don't need to change treatment. But let's do the first one. So can you use MRD negativity as a way to talk about discontinuation? So Jonathan Kaufman, one of my colleagues, has a series of 60 patients that he treated where if they were MRD negative at year two and year three after a transplant, he stopped their Revlimid. Now our practice as a group is, everybody gets Revlimid until either progression or side effects regardless of what MRD or anything else looks like. Jonathan said, I'm gonna carve out a group and we're gonna see what this happens. And the control arm is my patients, where patients get it forever. And so preliminary analysis looks like that works. At two years, nobody in his group has relapsed. Now we're going back and double checking all the numbers and the data and looking at progression-free survival curves to understand. But that kind of an approach may be useful to help us understand who needs to stay on versus who doesn't need to necessarily stay on. So that's one way that we could use MRD. I think the second thing is that can you use MRD to make decisions about treatment? And I'm not quite ready to say that somebody who goes from zero to a hundred copies needs to change treatment. Because when somebody goes from a CR serologically to an M protein of 0.4, I don't necessarily start them on treatment. So why would I think about this any differently? And so I think that's where the art of being a myeloma doc really kicks in. What do you know about that patient? Is it going from zero to 900, to 5,000 in the course of one year? That's somebody I would be concerned about. Or is it going from 10 to 15 to 20 over three years? That's somebody I'm probably not that concerned about. So the subtlety of how to use those numbers and when to use those numbers and when to pull the trigger, I think is gonna continue. This is why I don't worry about a computer replacing me. Because it's experience in time that helps you know how to do that. And quite honestly, most community docs don't have either of those. They don't have the experience, 'cause they don't see a ton of myeloma. And they don't have the time because they're seeing lung cancer and colon cancer and everything else. So this is where being tied into a major myeloma center is so key to knowing how to interpret that data and maximize long-term outcomes.

- That's great. Yeah and computer can't wear that jacket the way you're wearing, let me just tell you that. But so still he looks good and yeah, he's just like strolls out of Atlanta. Look at that, but I do want to emphasize that point because we have the privilege of hosting so many patient meetings and I think sometimes and at the IMF, we've been very excited about the concept of MRD. We've written blogs about it, we've done sessions about it. And a lot of patients come up saying like, "I need to know, I need to ask my doctor, am I MRD negative or not?" And I've had patients come up to me and say, "You know, I found out that I'm still MRD positive.." And they sort of feel like their life is crashing because of it. If there's one simple message to leave you about MRD is that it's not that simple. Let me just emphasize a couple of areas to help you understand what I mean by that. So we have some patients who will never become MRD negative but live a long and well life with myeloma. Our German colleagues just published a paper this last year looking at their greater than 15 years survivors. Almost half of them have never actually achieved a complete remission, let alone MRD negativity. So please don't think that it's MRD or bust, because that really isn't the case. Paradoxically, we have some forms of very slow growing myeloma where having a little bit of disease seems to protect someone from their myeloma coming back. I can prove this to you in the lab. I don't wanna get totally nerded out on you, 'cause I know Theresa's gonna say, "You're getting into your myeloma nerd phase." But I always say my wife loves the fact that I'm a myeloma nerd, right? She always says, "I love you're such a nerd." I'm like, all right nerds, nerds get it good.

- We didn't rule in high school, but we do now.

- Yeah, we didn't rule in high school, we rule now. That's right, yeah. Yeah, sweet.

- That's right.

- I wasn't really a nerd in high school but anyway, we'll get into that. It's a little TMI, I think this is being recorded too, sorry Jake. But the the point being is that if I took you into the lab, ironically, I can put a really slow growing clone of myeloma into a mouse and that protects that mouse from a more aggressive myeloma. So sometimes a little bit of naughty protects you from a lot of naughty, I think having a little bit of dessert saves you from going to the dessert buffet, is the way I put it, right? So myeloma's very complicated. So I don't want people to think that it's all about MRD negativity or not. In general, yes, achieving MRD negativity is a good thing. But Dr. Lonial said it beautifully, he said, in each individual patient you have to be looked at uniquely. We said this several times yesterday, multiple myeloma's called multiple myeloma for a reason. It really is different in every patient. Alright, I want to move to your second major prediction of the future. This whole idea of predicting in advance who's gonna develop myeloma. I mean, do you think Saga, and I know I mentioned briefly yesterday the ISTOP study in Iceland, you know, where we've screened nearly 90,000 people. We're gaining all of this incredible information. And I know it's a little bit premature to ask you, but this is the future of myeloma session. I mean, do you see us reaching a point in the future where we're gonna start screening people for myeloma and maybe most relevant to our patient population? Would we be starting by screening family members of myeloma patients? What's your thought about how that field is evolving?

- Yeah, no, that's a great question. And we are part of a project with seven centers that is trying to understand the risk of progression and smoldering. And at the same time on the side is gonna be looking at screening for first degree relatives of African Americans, because we know their risk is much higher as Ice-T told us.

- So you listen to Ice-T?

- Ice-T, it was good.

- Yeah, I'm from the south. We drink iced tea, no, it's okay. So I think, I think there will be patient populations where we do embark on screening. I think the question about methodology, 'cause I worry and Dr. Dispensier is probably our in the room expert on this, but if you're using mass spec you may start to pick up a lot of stuff that isn't really MGUS. And so understanding where to set those cutoffs, I think are gonna be really important. And that's where a study like ISTOP is critically important because they have the numbers to help us do that. But I do think first degree family relatives of patients with myeloma, I think we will eventually get to a screening process and I suspect African Americans will look at screening as well.

- And I remind people that, you know, when we determined how to screen for breast cancer, when we determined how to screen for colon cancer, it took decades to figure it out. And then it was very meticulous, right? We don't just screen every woman on the planet for breast cancer, right? We don't just screen every person for colon cancer. It's based on family history, on age, on gender. You know, I had to be screened earlier for colon cancer, 'cause unfortunately my father died of colon cancer, so we were trying to figure out those riders now. But I think most of us feel that the highest risk groups are patients like myself of African descent but also potentially family members. So the only other very pragmatic point I make here, because sometimes people leave a seminar like this and they start talking to their family about you know, should we be screened or not? Should we test or not? If someone is asymptomatic, meaning they don't have any signs and symptoms of myeloma, is that does require a discussion and some thoughtfulness because there isn't a recommendation to do that yet. And then honestly on a very pragmatic note, I think I mentioned yesterday that I had a family come in to see me where there were three siblings with myeloma and they had two other siblings who were considering testing. You know what I told those two siblings before we tested them. I said, "I suggest you get your life insurance an order now before we do the testing." I'm not trying to beat the system, I'm just trying to be very pragmatic that once you have MGUS, it's much harder to get life insurance. One of the most riveting conferences I have ever attended was the American Association of Insurance Medicine. I'm almost tired saying it anyway, no disrespect to anyone who's a member of the AAIM, I know it's a just riveting conversations. But I remember I met with them 'cause they said is there a possibility for us to ultimately insure people with MGUS? And they're debating that. But at present now, if you have MGUS on a test, it is gonna significantly impact your ability to be insured with life insurance and the rates that you might pay. So just very pragmatically, if someone's gonna go get tested for it, I might suggest that they get the insurance in advance.

- And I just want to go back to highlight something that you mentioned a moment ago, which is about the ISTOP study. So the ISTOP study first of all, is a phenomenal opportunity that Iceland is one of the few countries in the world where you could do this. Cause everybody lives sort of in the same place and you have access to, I mean I think everybody's had their genome sequenced in Iceland.

- Almost yeah.

- So I mean it's the kind of place where you could do this and it wouldn't, that study would not exist without the support of the IMF. So I think that's the first thing to say is, the IMF came out early and really pushed for this kind of a screening study to be done. And so it will tell us whether screening actually makes a difference. The challenge I have with ISTOP, is that it's a very homogeneous patient population. Very white, very northern European, all Vikings I think, and not Minnesota Vikings.

- Yeah, yeah, no I get it.

- But it doesn't necessarily answer the question about African Americans and screening, which I think is a separate issue. And I think we need to do that kind of work here to answer that question.

- And if only we had our vice president of development and philanthropy to later talk to us about what we're doing for Iceland. Sylvia will come and talk to us a little bit later, as some of you know, coming up in just a couple of weeks. And believe me, I know 'cause I've been training every day for it, a group of us are gonna be cycling across Iceland to raise further funds and to raise awareness of myeloma and for the project, the ISTOP MM, which stands for Iceland Screens, Treats or Prevents multiple myeloma and the project that we're doing. That being said, also our colleagues in Charlotte are just about to launch, and we're working as the IMF with them, about to launch a much smaller scale, but a similar kind of concept of screening population of African American patients in the North Carolina region. And so you're very right. ISTOP, had to be done at Iceland because it was the right place to do the testing and to understand it. They have a universal healthcare system, so we could test, look for things that otherwise we couldn't. But it clearly doesn't reflect the diversity of the planet.

- So if you're gonna use the Iceland biking thing by the myeloma doc activity index where we compare how fit each of us are, you get no credit 'cause it's flat. You can bike for a hundred miles, you get no credit, 'cause it's flat, you gotta go up.

- So, so...

- I'm just saying.

- If you've seen the landscape of Iceland, it's very much like a serum protein electrophoresis, right? There's lots, let's just say the M spike that I'm gonna be climbing is will be disturbingly high. But all right, there's my nerd gene being activated again. So Sagar, we have about three and a half minutes left and I just wanna give you an opportunity for us each to give a little sort of closing thought about anything else sort of looking into the future that excites you about myeloma.

- Yeah, I mean I think, and people have given this trial many different names, but for three years now we've been trying to put together a trial that basically takes all of the immune targets in myeloma and exposes a patient to those sequentially over the course of two years of therapy. And the idea of, I mean, we talked before about, if you hit with BCMA, does it make sense to continue to sort of flog BCMA? Well it doesn't 'cause myeloma cells are smart, and if you hit them with one thing for too long, in many cases it's gonna figure out a way to get around it. And so the idea of keeping myeloma off its heels and saying we're gonna continue to change the target. We're gonna continue to not let you evolve and hit you with every immune target we have. And right now we have five or six I think in myeloma, in a defined period of time, that's a trial we are trying to shop around right now and are very close to being able to open next year, where it's two years and then you're done. And the goal is to achieve sustained MRD negativity, hitting BCMA, CD38, FCRH5, GPRC5D, and using PIs and cell mods at the same time to sort of augment each of those different phases. That to me is really exciting because it's limited duration therapy. It's not like AL therapy where you're sick for two years. Most of these treatments are very well tolerated and we have the tools. So now that we have the tools that we didn't have two decades ago, it's our responsibility to put them together in a way that changes the paradigm and ultimately increases the fraction of cured patients.

- That's beautifully said. It's hard to add anything to that. But my only addition to that is that, I'm very excited about the very same thing, the sort of next generation of immunotherapy. I mean as we talked yesterday, the whole concept of immunotherapy, of engaging someone's own immune system to destroy myeloma is a brilliant concept. And it's now gone way beyond the concept to actually pragmatically having multiple therapies approved and more coming. I'm excited about the ones that are coming. I shared yesterday that, you know, there's no drug in myeloma we use today the way it was first introduced. Everything goes through an evolution. As that evolution happens, I think the fraction of patients, whether we call it cure or whether we call it long-term control off therapy, we can debate, but I think that fraction of patients is gonna considerably increase. And it's all under the tenure of what Yelak shared with us earlier too. That the patient engagement in these trials and in this approach is so important. 'Cause I said it yesterday, Theresa said it yesterday, "We don't treat myeloma, we treat people." And so being able to capture in real time the real world evidence as we call it, of the patient input, like at meetings, and in situations like this, where you tell us, 'cause I can look at your, as the nerdy scientist, I can look at your marrow and say, "Hey, you only have one in 100 million cells that are myeloma cells." But if you're feeling terrible, what's the point? So being able to do so in a way that supports your quality of life the way you define it, so that you could enjoy life the way you want to enjoy it, is really our ultimate goal. And that to me is a very exciting future of myeloma. And when Sagar and I started a myeloma, I won't tell you how many exactly years ago was, you know, as I mentioned yesterday, our average patient sadly lived one, maybe two years. But now we're seeing patients live longer and live better. Living life to the fullest is of course our objective.

- So

- Just for the record, that inflection in the survival curve, is when I started in the field.

- Right, yeah, okay, sorry. You know, it's the humility that always draws me to Saga. Thank you Sagar.

- So I wanted to highlight why you need a myeloma specialist on your team. This was not a prepared conversation that they have had. They have not rehearsed this. And for me, I always say a myeloma expert is someone you shake up in the middle of the night, like2:00, 3:00 AM in the morning and wake them up and ask them a myeloma question and they will be able to answer you, give you the answer. So these are why you need people like this on your team. So thank you.

- Welcome back everyone. This is going to be the session for approaches to relapse therapy. If you happen to be someone who is maybe within that first year of treatment smoldering or have monoclonal gammopathy of undetermined significance, let's just say MGUS for now on, you will be meeting in the club room. Have everybody find their seats? Are a couple more people still trickling in? All right, well, I typically would be in the newly diagnosed or approaches to treating newly diagnosed myeloma room because that happens to be my particular area of interest. However, because of our guest speaker who happens to be my BFF. Dr. Angela Dispenzieri is going to be talking on approaches to relapse therapy. And it's my pleasure not only to introduce her but to have worked with her for the last 33 years. Thank you. Come on up Angela. So Dr. Dispenzieri is at Mayo Clinic in Rochester and has been working in the myeloma space for that long, for 33 years. And she is amazing. Her patients love her. She actually works across the whole gamut of myeloma care as well as other protein related disorders. And so I will let you come up because she has way too many accolades for me to even remember, but she is my best friend so that's the most important one.

- And we all know Theresa has good taste, so I must be okay. Anyway, so hello, welcome. So the way they have it set up is that I do maybe 30 minutes of just going through some of the therapies. You probably heard some about these things yesterday and a little bit today. But we're going to go through that and then we have time for questions. 'Cause obviously those are often the most important things is really trying to personalize it for you. Okay, so my disclosures. Okay, so what we're going to do is just a little bit of background and I'm going to focus a lot on the immunotherapy because I know there's been stuff said about all the different bispecifics and CAR Ts or whatever, but it is kind of confusing. So I thought we could spend some time with that and again to general principles and then some recommendations because you know, an approach to relapse myeloma, there's no such thing, you know, because you're all individual. There are many approaches to relapse disease and so there's no right answer, there's no one pathway. You're all different and your disease is different. And so again, you know, there's some concepts that hold true but it's pretty hard to be very specific. Okay, so you saw something like this earlier and this is basically 77... Whoops. It went ahead by itself. Oh well, that's not good. How do you make it go back?

- [Speaker] Sometimes there's a slight delay on the button, but sometimes you just click it once, let it load and then it's good.

- Huh?

- [Speaker] Sometimes there's a slight delay when you hit the button. But if you hit it too many times in a row, it like skips ahead.

- Oh, can somebody make me it go back? If you can't, I'll tell you.

- [Speaker] We can go back. You want to-

- Back please go back one.

- [Speaker] Yep.

- Okay, so that timeline is basically showing you 77 years. There it is. Oh, it's funny. What's there is different from what's there. Okay, so 77 years and you kind of saw that this is not to scale, but you know, 40 years of not a lot of activity. If you look at the blue, we had melphalan and transplant that which we sort of put away even though Yelak had it at that time because that's what was there. And then the next 18 years there was some more action and we ended up having a number of different drugs, many of which you probably are well aware of and may have already had. Bortezomib, which is known as Velcade. Lenalidomide, Revlimid. Carfilzomib, which is known as Kyprolis. Ixazomib, daratumumab, pomalidomide. We have also... You have selinexor, isatuximab, autoleucel, teclistamab, we have lantamab and we're going to be talking about all of these, talquetamab and so forth. But you can see in the past eight years an awful lot has happened. And so that is really exciting. And when we look at our treatments, whether it's for newly diagnosed or relapsed, we kind of have 'em in little buckets sort of group. So each box is sort of a class, like they share something similar to each other. And so, you know, if you start in the left upper corner, you have what we call the alkylator. That's really the old fashioned kind of chemo, but it's part of transplant too. And some of it's perfectly good. We don't ever want to forget about it 'cause it can help. But then if you go down, there are things like what we call targeted therapy. Selinexor is something that was approved in the past five years or so. Venetoclax is another therapy that's targeted. It is FDA approved but not for myeloma. So a certain percentage of patients, about 15% of myeloma patients have in their chromosomes on their FiSH something called translocation . And it appears that the patients who have that translocation are extra susceptible to that medicine called Venetoclax. And so that probably will be approved and we can still sneak it in and get it for patients even though it's not approved for those particular patients. And then there's something called proteasome inhibitors and some of the names you recognize, of course corticosteroids, which everybody loves dearly, but we have our Revlimid and pomalidomide and thalidomide in one box. The CELMoDs are drugs that are sort of the next generation to the Revlimid in the pomalidomide or Pomalyst.

And those are not yet FDA approved but probably will be. And then we have all these antibodies. So the whole kind of right hand side of the slide is immunotherapy and we're going to focus more on that. But we have all these different antibodies and we have things called bispecific T-cell engagers, and then the CAR T cells. And so we have all these little pieces and as both Joe and Sagar just shared, you know, we're learning how to put it all together because there's so much that's new and what's the best order? Like how do you put the pieces together? You do one at a time, do you do this one first, the next one second. And so these are all questions that are being addressed and the better the therapy, the longer it takes to figure out if it's better or not. As you get better and better therapies, especially if you're looking to see, you know, overall survival when patients live as long as they're living now it takes a long time to get there, which is really good news. But at the same time to dogmatically say, A is this much better than B, it sometimes takes a little bit of work and effort to get there. So I just wanted to run through a few general principles, therapies change over time and then clinical trials make this possible. Outcomes. So outcomes like survival changes over time as new therapies emerge, people living longer and longer. But also, you know, if you have a certain regimen and it was used in people who've never seen a drug from that class before, it's going to work way better than if you try that same regimen in somebody who three years ago had that same drug and maybe it didn't work. And so there's all kinds of moving pieces that we look at. If one therapy didn't work well, it doesn't mean that another won't. Terms like overall survival and progression-free survival refer to statistical probabilities for groups of people and don't seal the fate of an individual. So you know, you have to give estimations and when we say, you know, progression free survival with this drug is let's say three years. That's true. If you had a hundred people, yeah, about half of 'em, you know, would be without progression at that time point.

But we can't pick out whether Joe, Mary, George, whatever, you know, whether they're going to be the ones that are still doing great on that therapy or that it, you know, it's not working so well for them anymore. So those are really important concepts. And then there's often no right answer at a given point of time because so much is happening so fast. Okay, so I'm actually going to start with a patient of mine, just to give you an example about relapse. I don't know how... Like are there people with myeloma for... How many have had myeloma more than five years? Oh wow, okay, good. 10 years? Good. That's great. So this is wonderful. So this is one of my patients who's a 17 year survivor and she had myeloma and she had what we called ISS3. So you know in that parlance it was sort of advanced myeloma and back in the day we were using mostly doublets. So Revlimid, she started with Rev/dex and what happened is her kidneys got kind of funky with that. And so she went on to Velcade dex and she had a transplant and she did achieve a complete response. Now, I'm going to go to the next line and the scale is different. So when she started, her light chains were 1200 or depending on which units you measure 12,000. But as we do better, we're using a smaller scale, like it goes up only to 200. But what you can see is if you follow the line, so we're going from time left to right and each of the words going up and down is another regimen. So you know, the bottom starts at year five and she had a remission for about... A complete response for four or five years. And then her disease started activating again. And so then she had another transplant because she was somebody who, quality of life, it rules. She's like, "I don't care if I have to live shorter, I want my life to be good quality." And I'm like, "Hey, you know, we're in this together, we're working together, we do what you need to be done." And so we had our second transplant. She definitely didn't want maintenance.

She's like, I want to ride my horses, I want to do this, I want to do that and I just don't want to mess with things. Okay. So we did well for two years, even after her second transplant, she relapsed. We tried something, we tried something, you know, a little bit of benefit. She went on a clinical trial, she then moved to, you know, Dara pom-dex, then we moved to Venetoclax. Now her numbers you notice are not at the bottom. You know, up is bad and down as good, but she's living with relapse disease. Her numbers aren't perfect, but she is having a great life. And so, you know, numbers are important and trends are important, but it was even said, you know, MRD sure it's a goal. On average, you know, if a regimen produces higher MRD rates, that's good, but that isn't the whole name of the game. It is that we're keeping the disease under control and that people are living their lives. And so, you know, she was sort of, you know, doing okay, not perfect numbers, but holding her own with different combinations with the Venetoclax. And then she went on a clinical trial with one of the bispecific antibodies. This one isn't approved yet, but she did that for a year and whew, her numbers did great. She was in remission and MRD negative even, but she had one of the complications that we know happens with these immunotherapies. She ended up with wicked infection. So she had to come off the clinical trial and she recovered from her infections and we said, "Well, let's just hang tight for a while." You know, in theory we're supposed to continue indefinitely, but we couldn't because the trial, you know, wouldn't allow it. But she went for a whole year with no therapy, still in remission. And then, you know, she started relapsing again and we tried a CAR T, it didn't really work for her, but then she went on good old fashioned carfilzomib or Kyprolis and it's a year and a half and she's doing really well. But this is a journey, you know, it's... You guys that have been around for a long time with this disease, I don't know how many have been in, you know, complete remission for the whole time or you've kind of had to dig into different therapies here and there, but you know, sure it's nice to just be in remission forever. And that's our ultimate goal of course. But people can live with disease as she is a perfect example. And so, you know, she... 12 years, 13 years after her first relapse, she's still doing well and as mentioned, not in CR but good quality of life. So let's talk about immunotherapy. So again, the whole idea here is we want to train or re-train the immune system to kill myeloma. Our immune system is to fight infection, but also it's supposed to do surveillance. It is supposed to keep these antisocial cells in check, these cells that want to be cancer or cells that are cancer. The immune system shouldn't let that happen, but somehow it does in myeloma and other diseases. And so the idea here is how do we train the immune system to work as it's supposed to work? And so a lot of what we do is with using lymphocytes and sort of these T-cells are kind of what we're really engaging in a lot with the CAR T and the bispecific T-cell engagers.

But here's a cartoon and it is kind of busy, but what I'm showing you in there in the middle is that big blue blob is the myeloma cell, the darker blob inside is its nucleus and then it has little red things around it. And those are little what we call antigens. They're little surface proteins that every cell has and there's a whole assortment of them and so forth. But what we do with immunotherapy, the goal is we say, are there coatings or decorations or antigens on the myeloma cells that are mostly only on myeloma cells and plasma cells? We don't want to have that same target, you know, in your brain or you know, your skin or your gut or whatever. Because if we're going to stimulate the immune system to hurt things we covered with this, we want it to be very specific. And so there are a number of different targets that are... They weren't put there to be targets but for our purpose targets that we go after. And then there are different ways that we go after it and those are the various types of immune therapy that we're going to go through. And this idea of this targeting, it's kind of that lock and key thing. Just not any lock and key are going to go together. Okay, so you got the naked antibodies, which are just that little Y-shaped thing. The four pronged Y-shaped thing is an antibody, it's a cartoon of an antibody and basically it's going after that myeloma cell. And so those naked antibodies, daratumumab, isatuximab, elotuzumab, I'm sure you've had at least one of these or many of you have maybe encountered, but they are recognizing different coding. So daratumumab and isatuximab, they recognize something called CD38. And so that's the declaration or the coating on the cell that it's going after. Elotuzumab goes after something called SLAMF7. When we get into a lot of the newer immunotherapies, and this is what we call an antibody drug conjugate, it's going after a coding called BCMA or B-cell maturation antigen. And that is something belantamab or Blenrep. And that had been FDA approved, but then it was taken away off the market because it didn't meet its ultimate endpoint.

There was a trial comparing it to pomalidomide and it didn't have better progression-free survival even though the response rates were better. But now there's some interesting data that are showing that maybe it may come back, it's still approved in Europe. But what it is you have that antibody, but there's a toxin, a chemical that is very poisonous to cells. And so you're bringing that toxin directed towards the myeloma cells to help kill. And so this is just an example, this is a DREAMM-7 Trial. Velcade Dex with belantamab or daratumumab. So everybody got Velcade Dex, but you either got the antibody belantamab or you got daratumumab. And the idea is you want the line to be higher. And so the red line on the left is the belantamab, what we call progression-free survival, alive and without the disease getting worse. And the blue line was the Velcade Dex with daratumumab. So very promising. And even on the right when we look at survival, again the red line is over the blue line higher than it. So that seems that it's better and based on this I suspect the drug is going to come back to the US. And there was another trial using pom dex with belantamab or Velcade, pomalidomide. And again the curves with belantamab look good so we will see. But moving to what we call the bispecific antibodies. So there are three drugs approved and what they have here is the purple is the myeloma cell and then the green is a T-cell. And then you have that funny Y with the four prongs and essentially that is the drug, these bispecific antibodies. One arm so to speak is reaching out and sort of grabbing onto the myeloma cell that has the BCMA on it and the other arm grabs out to the immune cell, the T-cell. And it basically is like, here look this is bad. You know, kill it, kill it, it's bad. And that's really the way these things work.

The two that are FDA approved, teclistamab and elranatamab are basically, again the target they recognize on the myeloma cell is BCMA, just like I showed you with the belantamab. And then there's something called talquetamab which is recognizing something called GPRC5D, another different coding. And so you know, we're trying to figure out how do you, you know, organize this? Like do you, you know... Once you've had one BCMA, anti-BCMA, can you have another anti BCMA? I think it was... I can't remember if it was Joe or Sagar who said it, but you know the myeloma cells get smart and you know, if you give it something targeting the BCMA, can you give it again a different thing targeting BCMA that may not work so well and... Or maybe you need a certain amount of time before that'll work for us. So just a little bit of a summary point about bispecific antibodies, the T-cell engagers. Overall about 60% of patients will respond to these therapies. Their myeloma numbers get better, their M-spikes get better and they tend to be deep responses. And if there is a response it lasts about a year and a half, that's an average, there'll be some shorter, there'll be some much longer. There's less what we call cytokine release syndrome. You guys heard about that already. Theresa, did they hear it or it's coming? Later. Okay. Cytokine release syndrome, which is basically an activation of the immune system that can make you very sick while you're getting the therapy, usually the first few doses. And so it has less of that than the CAR T does, which we'll talk about in a moment. And then a big thing, serious infections in about a third of patients. So like that patient I shared with you, she had a serious infection. We use intravenous gammaglobulin or immunoglobulins to sort of replace some of the immune stuff that we are sort of getting rid of with our therapies because, again, we're... Although we're stimulating the immune system, we're also blunting a part of the immune system. These are very handy because they're off the shelf, you don't need anything special. You know, your doctor can just have it infused in without any special preparation other than, you know, we do dose escalation and stuff because of the cytokine release and all that. And currently these drugs, you have to have had four prior lines of therapy in order to get access to these drugs. So it's later in the course of the disease and they are cumbersome because they really, most of them start out weekly and the way the trials were originally done, every week you come in for infusion. some are subQ, subcutaneous, so it's not that bad. But still not going into the doctor's office every week is a little bit of a bummer. There's every other week dosing after you get to a point and there's some that are, you know, looking at every four weeks.

But again, a small problem. Talquetamab is one of the drugs that has a slightly different mechanism in terms of bispecific. It's given weekly or every other week. It has less infection than do the other BCMA. Bispecifics and response rate is about 70%. But there can be troubles with taste and nails and skin because again that coating that it... You know, that surface marker for, that it's going after is also expressed on some of the skin cells and sort of the epithelium of the mouth. And so that's a side effect. Some people don't have those issues but others do. But just to sort of share, if we look at... So this is sort of a summary about bispecific antibodies and sort of where we are with them. We are trying to figure out when is the best time to use them. It was alluded to in the last session, you know, maybe it's part of first line therapy after CAR T, you know, all kinds of questions. Is that the best time? When do you use it? You know, is it better to use before CAR T after CAR T? Do you use it in combination with other agents? And what these little blue bars represent is the response rate in this sort of foray into using combinations. So the first bar showing 78% response rate is combining talquetamab with daratumumab and the next one is showing talquetamab and teclistamab and you know, these just various kinds of combinations and what are we seeing? So there's just a lot to learn and the data are emerging just about every day. And then finally moving to CAR T. So there are two FDA approved drugs. Both of them target that coating called BCMA. And again the myeloma cell is that purple guy up at the top. And then the green is this modified T-cell. And so it has the sort of the arms, it's two arms instead of four, but it is really part of the T-cell. It's not just an in-between. What has been done is that the cells, the lymphocytes are taken from patients kind of that procedure leukapheresis, it's very similar if you've collected stem cells, the machine is a little twisted, changed a little bit, but we're collecting those cells, it's one session to collect the cells. And then those cells are modified, they really...

The gene for this chimeric antigen receptor is put into them and those cells are grown up and then they're given back to the patient after some what we call leucodepletion therapy, just a little bit of immune suppression to make sure that they can find a nice space. And then basically they're there to kill myeloma. And again, the time from arm to arm they kind of call it, you know, from getting the cells out to then putting a product in is typically at least four weeks. There's some agents that are being experimented with that are, you know, more like a week from arm to arm kind of thing. 'Cause four weeks if you have an aggressive relapse is a long time to wait. And so that is potentially, you know, a drawback to the CAR T. But the benefits of the CAR T, we have very high response rates. 75% of patients improve. Currently no maintenance though Dr. Lonial Sagar told us that, you know, they are experimenting with using some maintenance in the setting. There's no steroids, no dexamethasone and, you know, we show benefit in patients who have had a lot of lines of therapy, but I'm not going to go into this very much, but there are risks. The most profound risks are the time, like right around the infusion. And so that's kind of a timeline, you know, kind of that first week.

And that's where a lot of times patients are hospitalized or seen on a very regular basis as an outpatient and have remote monitoring or whatever. And then there's some neurologic stuff where people can get delirious and confused and things like that and they can even have seizures and stuff. So nothing's for free, but most people don't get these things. But it is a risk. But the really interesting... And I know this is a busy slide, but the really interesting thing is there have been now clinical trials looking at using it earlier. So if you kind of focus on... Is this a pointer? Yeah, it doesn't matter. If you focus on the first two columns or column two and three, those are using ide-cel and the columns three and four are using cilta-cel. And what you're seeing is in the first column under KarMMa, those are patients... That was the original that got it approved, FDA approved. And the number of lines of therapy those patients had had was six. Okay? But they did another trial, they said well let's look using the ide-cel in people who've had only two to four prior lines. So the average number or median number of lines was only three. And then they said... Well, they didn't actually compare it, the slide is made up to put them side by side just for an illustration. But the expectation that I think many of us had is that there would be higher response rates and longer progression-free survival. But interesting that progression-free survival, meaning alive and not progressing, the myeloma not progressing, was really very similar. 12 months versus 13 months. Whether you were very delayed in your disease, had been through a lot of therapy versus whether you had it earlier, whether it was done, you know, within two to four lines.

And similar, the other product, the cilta-cel, same type of clinical trial. The original one, that second kind of light blue column, six lines of therapy was the median. The early was for this second trial or this other trial, two lines of therapy. But when you look at the overall response rate and the CR rate and everything, they're not that different. 95 versus 85%. And again, at 12 months the number of people progression free and alive is comparable. And so, you know, I personally was surprised. I would've thought, you know, it would seem that much better. But we need to learn so much more. We have to follow patients longer. But what this does... That trial gives us, or both of these trials, the KarMMa-3 and the CARTITUDE-4 is that the drugs are available at earlier lines. So up until about, I don't know, six months ago or something, it was that you had to have quote, failed four prior lines to get access to these drugs. Now you can get access much earlier, it's approved and insurance should cover it. So again, questions with CAR T in doc... When do you use 'em? We're not sure yet. We're figuring it all out. Again, do you, you know... We think it's probably better to be using this before the bispecific antibodies if it's... Especially if you're going after that same coating or same BCMA therapy.

But do you use maintenance after? Do you use it with other drugs? We're really excited about faster production, products that may be give us even longer duration of response. Products that could be made from the stored cells you have in the freezer that may be your second stem cell transplant that you haven't used and also new targets. And so we're learning a lot. So back to general principles, if we look at... So what I'm showing you in blue is the overall response rate of different regimens. So in each of the lines are going across horizontally. So the percent of people responding is the blue and then the green is the duration or the progression free survival. And if you notice that as you go further to the right, those are bigger bars showing you that those immune therapies, the talquetamab, the teclistamab, the elranatamab, the ide-cel, the cilta-cel, something I didn't talk about, which is a CAR T after that is not approved, but it is showing really good effect and it's after the GP65D target. all of those have really high response rates compared to our old favorites. You know, pomalidomide, carfilzomib, daratumumab is a single agent, selinexor and even the green bars are also going up. The progression free time is even better. And so it's very exciting how much has been going on in these past few years with just individual therapies offering much better outcomes. So the good news is that there are many treatment options. The bad news is there are many treatment options and the only way it's bad news is that it's confusing. You know, we can't say for sure sometimes do this versus that because we just don't know yet. But overall, it's great to be having so many options for patients.

And again, you know, as we think about what's our approach to treating a patient with relapse disease or even new drugs or approaches to treat disease, we're always thinking, you know, what's the tolerability of a regimen? What's the sequencing? You know, is it bad if we use this drug upfront because then we don't have it down the road? Don't know. How long do you use it? You know, we'd love to have limited duration therapy. How does that all work out? It's true in newly diagnosed, it's true in relapsed. And then even the dosing of different therapies, you know, again, we're learning with some of the bispecifics, you know, they don't really necessarily have to be every week. The ABBV bispecific, which isn't FDA approved is dosed every four weeks and it seems to work quite well. So again, a lot to learn. But then the other really important and interesting thing is that there's something called synergy. When you basically put sometimes two drugs together or even three drugs together, the whole is greater than the sum of the parts. That's where I have one plus one is, you know, greater than three. It really is... Sometimes there is an interaction between these drugs and they really are... It's important to have them together. And then there's what we have clonal tides where disease sort of goes through sort of different phases that, you know, when you have your myeloma, we talk about it being a clone, but each of your myelomas, it sort of has its own little evolutionary life where mutations occur and it derives slightly different features and characteristics. And so, you know, you may be respond...

Your disease may be responsive to one therapy, but then it's not responsive down the road because again, those sensitive clones have basically been killed. And now you have the resistant clones. And so there's a lot to think about. I would direct you... I have some slides on, you know, how do you treat first relapse, second relapse. It's a bunch of just flow charts. But we put at Mayo out there for anybody to look, you know, how do we deal with first relapse, your second line off study and you know, different conditions, refractory to lenalidomide, not refractory, you know, second or later relapse. You can just go to those web pages. But for me to talk through it, I think you'll all be asleep very quickly. So I'm not going to really do that exercise, but I'm more than happy to, you know, talk through specifics and clarify things. But that's kind of the approach. But I want to leave you with the idea, I mean the future is bright. There is so much going on in this space. I've been in this business, you know, for almost 30 years with myeloma and it's unrecognizable in terms of the duration of life that patients enjoy, the quality of life that patients enjoy and just the opportunity. So with that, I thank you for your attention and I'm happy to answer-

- [Theresa] So with that in mind, we've got hands already going up. This is our time to do a Q and A and something people I want for you to do, knowing that this is complex and only going to get more complex, make sure that you are creating a journal, a timeline of your own treatment history because you're going to need to know that. Eric.

- [Eric] Thank you. So regarding CAR and trying to extend that time before the disease comes back, Dr. Lionel mentioned that his patients, he puts 'em on maintenance. I read a journal article a week ago that talked about CAR E. So it was some sort of enhancement, some sort of additional treatment that was given after the CAR T was given to do just that, to sort of keep the T-cells up, alive, engaged because they die off at some point in time, right?

- Yeah. And so I can't say I know that specific article, I apologize and I could look and give you more, but I can tell you just in general stuff 'cause there are things that are, you know... You see at meetings and then when they're published they're a little different. But, so there are different constructs that are, you know, trying to actually keep things around longer. There's a couple of things out of China where they have longer persistent type of CAR T, so that's one. There's work using like what we call checkpoint inhibitors, you know, trying to upregulate the sort of the immune system so the CAR T may work better. You know, the Revlimid data. I think in some, we know that it's immune enhancing, you know, for those few patients it's sort of out of fashion to do an allogeneic stem cell transplant in patients with myeloma. But you know, we saw that if a patient had an allo and you give 'em a little Revlimid, you can put them back in remission if they're relapsing after. So there's all these different ways of trying to modify, you know, the immune environment and either through persistence or through just, again, affecting the milieu. But I can't specifically address that article, but happy to look it up and go over it with you if you like later.

- [Theresa] And I apologize, I should have mentioned, Eric is one of our support group leaders.

- Sure.

- [Theresa] And he's on top of it, man.

- Yeah, well-

- [Theresa] I'm telling you.

- There you go.

- [Attendee] Yeah, thank you for your talk. But I have a question about the synergy idea. Batolime, I am probably saying his name wrong, the old pioneer-

- Barlogie, Barlogie. Yep.

- [Attendee] Yeah. Barlogie, he always believed in like eight or seven, you know, treatments all upfront. But it seems to me like over time that was sort of drifting You know, two is better than one, three is better than two, four is better. So I'm wondering if anybody's looking at his old stuff. That was about eight in the beginning.

- Yeah. And so, you know, the drugs that he used, they were all like very similar to each other. There were a lot of alkylators and there are a lot of medicines that we don't use anymore. But his concept of the idea of using everything that you know that you have upfront, do it sequentially and you know, then do some maintenance and consolidation is an approach that was just talked about, you know, before the break. The idea, you know, if you kind of keep at it and you come at it from all different ways, you know, the hard thing is you don't know until you get there. You know, whether you're sort of by doing something you're blunting you know, you're having the opposite of synergy, you're having some kind of antagonism or whatever. And that's why these things... You know, people can make stuff up all the time, but you really need to do clinical trials to understand, you know, is this really better? And so, but his concept, which is really he borrowed from acute leukemia is very much the approach that people are taking and going more in that direction. But the drugs used are just obsolete at this point 'cause we have better stuff. Yes. Theresa.

- [Theresa] I have a question on your philosophy of when to treat biochemical relapse.

- Yeah.

- [Theresa] You know, we hear, okay now with a four drug regimen on newly diagnosed, let's hit this thing really hard.

- Yep.

- [Theresa] Then with biochemical relapse, you hear, well, let's watch and wait.

- Yeah.

- [Theresa] And for me sometimes that feels in conflict with, let's catch it early or-

- So again, that was a little bit... It's a great question. You know, it was touched upon at the last session as well. You know, most of us don't treat with just biochemical relapse. The concern number one is that you don't want to hurt the person. You know, we can... As a physician, you know, we can flog patients till the cats come home. But that's the antithesis of good quality of life and all of the rest. There is precedent where, you know, more treatment can be harmful. Again, in the modern day we haven't shown that, but certainly in the old days when we only had alkylators and things, we found that we were giving people, you know, high rates of acute leukemia and things like that. And so, you know, you always, you want to put your toe in at the same time. The other thing Joe also shared, he said, you know, "Sometimes maybe a clone is coming up a little minimal residual disease, but maybe it's not an extra wicked clone and maybe its presence is suppressing, you know, maybe one of these more aggressive clones." So we can theorize and hypothesize as much as we want, but we don't really have the answer. And for something like that, you know, the endpoint really would be overall survival you'd have to measure. And there are people looking at various things, you know, when do you stop therapy, you know, a little bit treating with, you know, as you're gradually coming up. But those trials literally to get a good answer is 10, 20 years 'cause patients are living longer and longer. And so it's a very hard thing to address. But, you know, we don't treat MGUS, we don't treat early smoldering. And maybe... Certainly you never want to treat MGUS, period. I mean, I can't unless it's some kind of magical, you know, hormone or you know, a leaf to chew or something. But, smoldering, you know, maybe we'll creep back and treat more and more smoldering. So, but it's that balance of not trying to do harm but it's a great question that just doesn't have a perfect answer. The other is the reliability. If you treat somebody, what's the reliability? You know, you stick a needle in the bone marrow and myeloma's patchy, you know, so you are MRD negative here and you know, then you're there. It could be, you know, a little bit positive or something like that. Or again, when you do a immunofixation test, those are not very specific as the immune system is regenerating. You can get little clones that weren't even necessarily your original myeloma clone and you don't want to be treating that, right? And so again, it's also in part the measurement tools that we have to sort of follow those things and to know that we're actually not just flogging a patient but doing something that's actually beneficial to 'em. Yeah.

- [Attendee] So I'm always really intrigued by the gap that exists between centers of excellence and community oncologists. And as I watch this, I see first off incredible information and data, but it's also very overwhelming. And I think to myself if I was a community oncologist keeping track of all these things associated with every other solid tumor out there and other things, right?

- Bingo.

- [Attendee] So what do you see as a, you know, potential paths to help get more of that expertise out into community oncologist. And then secondly, I think you're seeing more of the treatment options that you even referenced being available in community places because these are not... Some of these are not highly intensive the way that they used to be in terms of you'd travel to a certain location to do it. So you know, I guess the aspect of that question is are you seeing more and more experts or specialists making their way into the community environment?

- So I think, you know, Yelak was saying that he wants the, you know, the IMF to make available to all patients that kind of expertise and you know, what mechanism is there to do that? I agree. I mean, you know, I can't fault a community doctor, you know, for not knowing everything about every cancer. I mean it's a lot. But I think that there is a role for referral. You know, it doesn't mean you have to be treated at a center of excellence, but if there is one, you know, within reach to potentially go to, I think that that's an opportunity in the current day. I think that, again, there is... You know, we do education all the time. We, you know, speak at various centers, but it is a lot even to go to a community doc and expect him or her just 'cause they heard something once for them to remember everything. And so again, I think that that's where IMF is so important in really trying to sort of spread knowledge to patients and, you know, have them consider or have, you know, the info line to sort of have some of the nurses say, hey, you know, maybe you want to like... To get an opinion somewhere, but... And you know, every day people are sending emails, you know, "I have this tough physicians" that you've never met before. You know, "I have this tough patient," you know, "What do you think?" There's more and more with virtual kinds of consults that was big during COVID. It's harder across state lines nowadays. So it's challenging because if you have tons of, you know, financial resources, you know, you can tour the country and, you know, get experts everywhere. But, you know, most people don't have those resources. And so it's not very democratic in getting, you know, the best opinions unless you just so happen to live in a place where there is an expert center.

- [Theresa] And I'm going to just put a plug for our advocacy team. That is an area of advocacy that needs to happen is to be able to have a cross state line on a federal basis, medical consultations.

- [Speaker] Got it.

- [Attendee] Absolutely. And thank you for your presentation, really appreciate it. So I noticed in your case study at the beginning it was t . On t I'm just kind of curious if you are willing to share how many here have the t translocation. All right, so-

- That's a high percentage.

- [Attendee] My question is, when I learned I had this, you know, it was opening some doors.

- Yeah.

- [Attendee] But also I heard from one expert or another that, "Oh this one, you know, you don't get as deep response or this one..." So that kind of presentation that you showed for that one individual I've been trying to find. And so how do... Are there databases of, I'll call 'em user stories, you know, or patient stories that show what the progression is. And I'm t what worked for this person and then kind of related to that and specialists, you know, I tried... I knew there was a lot of research done at Emory Winship on t

- Yeah.

- [Attendee] So it's like, how would I access those doctors? It would be nice if I could do a consultation across state lines. I do have Southwest points. I could go to Atlanta, I guess. And then kind of wrapping that up is other... I did see at ASH last year, some was mentioned as a research done, I guess in Australia and the UK and just wondering if just the t landscape, if you can comment on that.

- Yeah, no. So, again, anybody who's immersed in myeloma knows the t story in myeloma. You know, there was a trial, the Bellini trial, which was doing Velcade and Venetoclax in all comers, but they did the subset of the 11;14 and, you know, they saw that there were higher response rates in the 11;14. Well, actually across the board higher response rates. But there were more deaths in the group that didn't have the t or upregulation of BCL2. And, but clearly there is an improvement. So you don't have to go to only one myeloma center per se to get information about that. There's literature published and so forth. So I think that any community doctor, could read these papers or whatever and you know, you have to get authorization and there's a little squiggling or maneuvering to get it. But you definitely can get it or go on a trial and there are a number of different BCL2 inhibitors next generation that are in research and time will tell, you know, will they get approved and so on. But again, I'm not saying that for example in myeloma that it should necessarily be first line, but maybe it should for translocation patients, certainly in the amyloid space, which is a cousin to myeloma. About half of the patients in that population have that translocation and it's really moved in, in a big way into that space even though it's not approved and their clinical trial's ongoing so we can get approval for that. So again, you don't necessarily have to go to the place where the research is happening, but you need to go to a place where they know that such a thing exists and that gets back to the center of excellence and you know, a community doc, it's a little challenging for them to know everything about every cancer. I mean myeloma, although second most common hematologic malignancy compared to things like breast and colon, lung. Phew, it's, you know, this big. So that's where you need to get some expertise. Yes.

- [Attendee] Good afternoon. Thank you very much for your presentation. I'm a over 12 years survivor of high risk myeloma. I have to say I've been very lucky in my un-luckiness. I've benefited from a lot of treatments most recently Carvykti, which I think is really a science fiction, futuristic treatment. I'm very... I recommend it to anybody who can qualify. My question is, what is in store for someone who relapses from a CAR T-cell transplant? Are you eligible for a second CAR T-cell transplant or do you go to bispecifics? That's of course on my mind. And I have a more specific question. I know there was an Israeli study where they combine both teclistamab and talquetamab alternating, if you know the results of that. And have they done anything to mitigate the ophthalmological side effects of those bispecifics? If you know anything about that?

- Well, the bispecifics don't have eye things. That's belantamab. So that's the antigen-

- [Attendee] Oh, thank you.

- Antigen drug conjugate. But in terms of these combinations, you know, again, I showed you, you know, some of those blue bars were some of the preliminary information on these different combinations. Most of these studies you mostly have just response and the, you know, the follow up is 10 months. This year at ASH or you know, at the IMS meeting, we'll probably get more follow up but it's hard to say anything really very specific about these things. It's just, it's interesting, it's promising, but where does it all fit? It's just too soon to say. In terms of what happens post CAR T, you know, there are definitely options and part of it depends on what you've had previously. Again, you know, the lady I shared with you, she had had prior BCMA, she had had the bispecific first 'cause that's all that was available. She wasn't eligible for CAR T at the time and you know, so she had the bispecific, it did well by her, but we did... 'Cause talquetamab wasn't available, we didn't have a trial and you know, so she's like, "I want to try the CAR T." It had been like two and a half, three years between the two anti BCMA. It did nothing for her. But she went to Carfilzomib, you know, a drug that's been around now for a decade and that's working well for her. So kind of looking back and what Theresa said about knowing what your therapies are, you know, you don't have to like quote them by heart, but if you could have them written down when you go to the doctor and sort of... That's really important. That's like the most important part of a consult that I have with a brand new patient that's multiply relapsed. I want to know those details. I want to know, you know, why did they give up on therapy X, maybe there wasn't a really good reason to, you know, and so you can circle back to that. But again, in this space to do, for example, Talquetama would poten... If you haven't had that, that's a bispecific. Again, not against the BCMA antigen, that would be something of interest or a clinical trial with something targeting a different coding might be of interest. But even just looking through your, you know, your history. Is there something that we A, missed or you know, maybe you used it but maybe now it's been, you know, 10 years since you had it, maybe it'll work again. So it's a little bit like detective work and a puzzle solving and then also just looking what's on the horizon.

- [Theresa] All right, so we are actually at time, but I'm going to take one more question and take a couple of minutes out of your break and the transition time between rooms. Malcolm is also one of our support group leaders.

- [Malcolm] Yeah. I have a different question. Someone who's been in remission for some time hearing all of this and becomes extremely nervous about when... Oh my God, when is it going to come back? What do you say to them?

- Yeah, I mean, you know, I think Yelak really pointed that out, you know, living with myeloma, it's hard. And you know, I say, look, first of all, you've been in a remission so long, that is a great prognostic thing. You know, the likelihood that you're going to get in another remission, deep remission with whatever we do next is very high. And so again, you know, a prognostic thing, you know, we talk about FiSH, cytogenetics, LDH, extramedullary disease, yada yada, but a long remission duration, you know, is also a very positive good prognostic marker. So, you know, you try to reassure people and you don't want the myeloma to kill you the day you have the diagnosis. Emotionally easier said than done. And some patients are masterful at, you know, only thinking about it like the week before the appointment kind of thing, you know, and they just live their lives and they sort of forget about it. But it is a challenge and sometimes, you know, counseling or whatever, but you want to... You don't want myeloma to, you know, get the satisfaction of taking your life in a different way, taking your emotional life. But that is a challenge.

- [Theresa] And I think you asked a really great question that everybody from smoldering throughout the journey really struggles with. And that's why we started the Smolder Boulder group for people who are living with the emotional or psychological challenges of myeloma without having myeloma, without having the symptom, physical symptom burden. But it is, there has to be a day-to-day strategy for working with some of that anxiety, that stress. I know Tiffany's going to talk a bit about that today also, along with some of the other side effect management tools that we have put together as a nurse leadership board. So with that, I believe we are at time, if not beyond time, but want to thank Dr. Dispenzieri for her expertise. want to thank you for your participation and your questions. And we'll be transitioning from the newly diagnosed. We'll be coming back in and we'll be getting started with the next part of our session.

- Thank you so much, Yelak. They always complain, right? They give me 20 minutes and then they say, "Oh my gosh, you're going on and on and on." And you know, Dr. Joe, it was not me. Are you keeping count of the time? All right. It is such a pleasure to be here, all of you. I started August 14th, 2023, so I've just completed my one year anniversary. This was this past Wednesday. And to say that it has been a whirlwind and the most gratifying, rewarding journey is an understatement. I have been on the road pretty much for the last year or so and you know, I travel almost seven days a week, if not more. And cumulatively, probably in the last year, I have been in town for about three weeks in total but I wouldn't have it any other way. And I have been to, this is my fifth Family seminar, Patient & Family Seminar in a year. I've been to seven regional community workshops and I've probably met close to about, I would say 15 to 1,700 people, one-on-one, across the country and internationally. I was in Madrid. We have a Global Myeloma Action Network and you know, we also, you all heard about the International Myeloma Working Group. I met our clinicians, met our European partners, and it has just been fantastic. Yesterday morning when I woke up, I felt a little bit different. You know, these are long days. We do a lot of work. We are out there, meeting a lot of people, doing what we are supposed to do for the IMF. And while I was in Minneapolis, while I was in Boca this year, while I was in other states, cities, you know, I walk into a room just like this and I have to introduce myself. They don't know me. I have to introduce my work, I have to introduce my team, you know, talk a lot about, and I have trepidation, right? Are these people gonna like me, not gonna like me? How is this all gonna shake out? Am I gonna see them again? If I call them, are they gonna pick up my phone call? If I email them, are they gonna respond? Yesterday morning, I woke up at 5:30 and I looked at myself, I felt very different. I was like, "Wow, what is going on? I was really tired Thursday night. Why am I feeling this way?" Can any of you guess why that was the case? I was roaring with energy, extremely excited to be here with all of you. Anybody wants to take a guess why that was the case?

- [Audience Member] Full moon?

- Full moon? Home-court advantage, y'all. Los Angeles, this is home for me. I am with my people. I pretty much know 80% of the folks in this room and the rest 20, I'm going around meeting all of you, right? It was fantastic. Very exciting. And for the 20% who don't know me, I'm going to introduce myself now. I am the Vice President of Development for the International Myeloma Foundation. I've been here for about a year. My job is to secure philanthropic support and resources for the IMF through a variety of diverse mechanisms. And I'll talk a little bit about what that is in a second. I am not alone in what I do. I have a fantastic team that does this work with me and I have them here right now. Matt and Kate, can you actually stand up? They're right in the back. And I also have Kim. Who is not here today with us, she had to be at a wedding, at her best friend's wedding. I also have somebody by the name of Amirah Limayo, who's been with the IMF for a very long time. Amirah, can you actually stand up? There she is. Amirah helps us with our grants and foundations, and our team is growing. We have a lot of work to do. I cannot do this alone. I cannot do this just with executive leadership at the IMF. I cannot do this just with my team. I need each and every one of you. I need each and one patient across the country, across the world, care partners, clinicians, nurses, anybody who cares about myeloma to be working with the IMF on this. I also have the incredible honor of working with dedicated volunteers from across the US and from across the globe. And you are all going to be that very soon, if you aren't already. So, what are the three ways for us to engage with the IMF? First and foremost of course, is philanthropical. We are a nonprofit organization. I've had conversations with a lot of you at the reception, throughout the course of this last couple of days. How do you guys do this? We are part of other boards. We are part of other organizations. We have family members who have other sorts of, you know, cancers. No other organizations has patient and family seminars, convenings, conferences, like you do. We bring you here to the Hilton Universal. We make sure you're fed. We make sure you're taken care of. We are a patient-centric organization. But to do this, we don't climb up the tree to get the money, right? Somebody has to ensure that we are getting the resources to continue to advance our mission, our work, and our efforts. So, philanthropy is extremely, extremely important. And you can obviously, you know, there are multiple ways for you to do this and I'll get into a little detail as I'm going along. Volunteering is also very important. I was talking to a patient who was here from San Diego this morning. Newly diagnosed, you know, she's obviously still working full-time. Not everybody, just like myeloma affects everybody very disparately, we are not look, I'm not looking at everyone in this room and saying, "You all have to open up your wallet, open up your checkbooks, write a check." There are multiple ways for you to step forward and help us advance our work. If you have skill sets, you have all been either, you know, financial analyst, a lawyer, you're a venture capitalist, you have done, you have accomplished. So there are skills that you have in your, you know, at your disposal. You can reach out to me, reach out to anybody at the IMF and say, "Hey, I'm interested in this. I heard Yelak speak about data initiatives that you have going on at the IMF. You have a fantastic grassroots advocacy program that's coming up. I would like to lend my voice, my talents, and my skills." You can also help the IMF, be a volunteer in terms of like talking to other patients, other care partners. And again, I'll get into a little bit of details with all of that. Intellectual capacity, as Yelak mentioned to you, we are still transforming. We are at a critical juncture at the institution right now. We are really revamping what is it that our board of directors could look like, what kind of people do we have on the board. We are looking at pipeline building, even, for the board. We are at the point of thinking through a patient advisory council, we are thinking about a president's advisory council. This is all, we're making sure people are coming in one step at a time into the organization. Typically, at the reception on the Friday evening, I have an opportunity to do an informal talk with Robin Tuohy and with Yelak. But yesterday, all of you were just guzzling that wine from the bar. Didn't have a chance. You know, we were like, "Let them all enjoy and disconnect with each other." But Yelak didn't become the president and CEO of the IMF, like waking up one day, because of his skills. He was diagnosed at the age of 25, as you all heard. He found a support group in Dallas. He became a support group leader. He was heavily, heavily involved with the IMF. He went to all sorts of patient advocacy programs. He went to American Society for Hematologists. That happens across the country, it's been happening in San Diego. Being an advocate for the patients on behalf of the patients, for himself. And then, he became a member of our IMF Board of Directors, you know, I think it was in 2015. And in 2021, the board unanimously voted him to become our president and CEO. You have heard from Robin Tuohy. You know, she didn't become the vice president of support groups, waking up one day. Her husband Michael Tuohy was a patient. They got on, loaded their dogs, their kids into a Waco, went around the country, city to city, establishing a support group. And through the continuum of years, they have been engaged with us for how many years now, Robin and Michael?

- 2001.

- Since 2001, 24 years. Slowly, through the ranks. They know everybody in the myeloma community. And Robin said, "I want to make my passion into work." She's leading our support groups across the country now. So, there are multiple ways for you to come closer and closer with the IMF and help us move the needle forward. So, let me talk a little bit about philanthropy, right, because this is obviously the most critical part. When I came onto the IMF a year ago, our budget is anywhere, depending upon the year, depending upon the programs, initiatives, projects, and what we have going on, could vary between 15 and $18 million. About 80% or 85% of that actually comes from, thankfully, to our pharma partners. We are very, very grateful to them. They help us. Let's give our pharma partners a hand, actually. We are very grateful for them because they do sponsor us for all these events and they make this possible. But, you know, myeloma is disparate. Anything can happen any day. You know, pharma, as much as we love them, they love us, they do this, philanthropy helps us to move the needle with unrestricted funding, right? We are visionary. There are bold ideas for us. We want to accomplish a lot in this next 10 years. One of the things that you may or may not hear from Yelak, from Dr. Joe, and from the IMF leadership, we are really accelerating our efforts to find a cure. We want to make sure the fathers, the sons, the mothers, the daughter-in-laws, you know, sitting in this room, who are patients, continue to live and enjoy life to the fullest and we don't want to lose any of that. We want them with us. But it's not gonna take a miracle. It's gonna take science, it's gonna take research, and research and science requires money, right? So, we need the community to step forward. How are we going to accomplish this? So one way you can do this, you know, you are like, "Oh my gosh, I'm interested, but I don't have that kind of resources. But I do want to do something for the IMF." The peer-to-peer fundraising model is very effective. This is something where you can start from scratch, from your ideas. Something that you're already doing, you know? Maybe every year during your birthday or your wedding anniversary or kids' anniversary, something that you do in the summer, you know, for fun in your community, you can turn that into a fundraiser. I have got Kent Oliver in the room here somewhere. Kent, can you put up your hand? There's Kent. Kent is a 10-year myeloma patient, survivor now, and from Hattiesburg, Mississippi. For the last 10 years, Kent has been organizing an event called Laughs 4 Life in Hattiesburg. I was just there three weeks ago. That event got a 1,000 people from his community. It's a comedy celebration. He had a VIP reception with 250 people. These are people that he's grown up with, lived with, worked with, people who care about him. I often get questions from our community. "I want to do this for a patient, you know, but I don't want to offer because I don't know how they're gonna take it." It is sensitive. People in your family, in your network, in your work life, they want to help you. When you ask them to support you, you're not taking away anything. You're giving them the opportunity to do something for you. So, get them. Get them along in the ride. Make them feel a part of your journey. You don't have to do this alone, right? So, a peer-to-peer fundraising model is fantastic. It could be something, you organizing just a dinner at your home, you know, and saying, "Hey, 10 people come, 100 bucks per person. Let me talk to Sylvia. I'll bring somebody from the IMF, talk to you a little bit about what myeloma is, what I'm going through, and then we'll have a fun time." There is Ron and Sheree Pask in the room. Ron and Sheree, can you put up your hand? There you go. That's Ron and Sheree Pask. They're here from Clark, New Jersey. For the last 12 years, Ron and Sheree have been hosting a 5K run/walk called Miracles for Myeloma in Clark, New Jersey. They raise funding from that and they actually give it for a Brian D. Novis senior or junior grant that helps us move the needle on research. So, and you know, it is very noble. They want to do this. They want to make a difference. They enable, they empower their community to come join them in this journey. So again, this is your idea. You could do anything. You can organize a dance-a-thon, you could organize a concert, you can organize a bake sale, you know? I was just talking to a lady yesterday, it's her fifth anniversary from a stem cells transplant this December. That's around her birthday. And she said, "Hey Sylvia, I really want to, I walk, I do a 5K for another organization. And hearing you speak in Charlotte, I just realized, why am I doing all of this for another organization? I want to do the same 5K run/walk, get my community, I'll organize it, and we'll support the IMF," right? So anything that you're already doing, we can help you amplify that even more. Yes, that's right. Oh, I was correct. We also have something, you know, peer-to-peer fundraising is, again, not everybody's cup of tea, right? It does require some amount of work, both from you and from us. We have to set up a webpage, blah, blah, blah, X, Y, Z. Not everybody has a time, energy to do that. You could simply give us a check. You could start with as less as $25 a month, $50 a month, $100 a month, make a $1,000 commitment a year. You probably go to Starbucks, right? Your Starbucks maybe costs even more than that if you get two caramel latte with whatever toppings you all get, right, at Starbucks. So, allocate that money to the IMF. Say, "You know what? I'm gonna make this commitment. I'm gonna give 100 bucks, 200 bucks, 250, but make it a recurring donation for us. Because when we know we can count on you, month after month, year after year, we know we have that funding that we can allocate to something that is the institution's greatest needs. We have something called the Hope Society. Kate Fitzpatrick, who just stood up and you've already probably met, leads our monthly and annual giving program. Please talk to her. We are really revamping, there are benefits associated with monthly and annual giving that you can actually take advantage of. Last but not the least, the transformative gifts. These are the gifts that's a moonshot ideas. We have stuff that we really want to do with research. There is stuff that we really want to do with our support groups. There are stuff that we really want to do with advocacy. There's things that we want to do with M-Power and our education. So, these need a lot of more commitment. These require bold visionaries who are in this room, you know, listening to me say about all this stuff. You've heard about us speak about Black Swan Research Initiative that was launched in 2016. It was somebody like yourself who was sitting in this room, got an idea, spoke to the leadership at that time and said, "Hey, your research portfolio is actually not that great. I want to do something. What are some of the things IMF wants to accomplish and where are the gaps, and how can I come in and fill the gap?" This individual gave us a transformative gift at that time, a multi-year pledge. We were able to launch the Black Swan Research Initiative and because of the Black Swan Research Initiative, we now have the ASCENT trial, the CESAR trial, the iStopMM trial. Each completely blew and knocked us out of the park, right? So, you just never know what your support can help us get to. Again, this is something that you can have a conversation with me. It starts off and you can keep thinking. It is not an overnight thing. We are partners in this together. I've already spoken to you about Laughs 4 Life. You know, Kent has been doing this for eight years. That is, again, that is the amount that the IMF has been a beneficiary of. He's raised a lot more. I spoke to you about Miracles for Myeloma. Ron and Sheree have been doing this for about 12 years. I am leading the inaugural cycling expedition in Iceland in a couple of weeks. This is a group of fundraisers who are patients, care partners, clinicians, and nurses. I know a lot of you heard and a lot of you spoke to me about this. You're all, some of your cyclists, right? You all cycle every weekends. You're doing this for fun anyways. You're doing 35, 40 miles. Come talk to me. If you're doing something like this for your hobby, you want to fundraise, you have a great community, you have a network that will back you up, we will help you get set up. It's a very fun event. This year is six nights and seven days. It's a jam-packed schedule. Each of these participants bike for about 40 to 60 miles a day. They get to visit the deCODE Genetics Lab at the University of Iceland. They get to hear from Dr. Kristinsson, Sigurdur, who's one of our scientific advisory board members in terms of like how the research in Iceland is going, how the partnership is working, so it's really, really excited. We do have a waitlist for next year, but we might do it twice next year because of the interest we are getting. So, if any of you are avid cyclists in the room, come talk to me. I would love to have you because yours truly goes but doesn't bike. I only sit on the bike for photo opportunities, okay? I already spoke to you a little bit about the monthly and annual giving. So, did speak to you about the Black Swan Research Initiative. Something that, you know, I want to put a plug in for all of you is the aspect of legacy giving. While you're going through a myeloma journey, you're probably not that liquid. You know, you're doing a lot of planning for yourself, for your family, for your near and dear ones, your grandkids, depending upon where you're in your life. But some of you do have assets, you know? It could be your estate, it could be stock options. It could be something that you've invested while you had a flourishing, thriving, you know, corporate career. Please talk to me. We would love to be a part of your philanthropic priority. Include the International Myeloma Foundation as part of your will. Please give us, talk to me about your IRA distribution. It's tax deductible. Because if you cash out your IRA, it's very high tax. If you give it to a non-profit like us, you don't get taxed on it, so it's a great way for you to cash out your IRA and actually make IMF the beneficiary of it. So, a lot of you are also still employed. You're working. We would love for you to talk to your employer and see if there's a matching gift option at your organization. Some employers match you one on one, some employers match you two to one. Whatever you give, they actually double up that gift for you. So, please go back and say, "Hey, I would love to give something to the IMF. Is there an option?" Talk to your HR beneficiary. Talk to your HR person and they should be able to support you. We have a Iceland cycling expedition participant, and his company, a lot of his coworkers from his company actually donated to his fundraiser. And then, the organization found out about it and now, they're actually matching all the people from his organization who supported him, they're doing matching gifts for that. So, you know, we actually multiplied that gift, his support, his participation by threefold if you know what I mean. I do want to speak a little bit about a couple of things that's coming up this year. How many of you here are actually part of the support group here? Can you all put up, raise your hands? Okay, that's quite a good chunk, Robin. Yeah. So, it's our Support Group Leadership anniversary summit's 25th anniversary here. We are running a fundraising campaign to help Robin and her team scale on her work, make sure she's able to do all the stuff that she wants to really accomplish. Compared to what they do for all the 160 support groups across the country, this goal is very minimal, right? This should be three times more than, but this is a test run. And we have actually, as of yesterday, we have raised $240,000 towards the 250,000, yeah. So, congratulations, Robin.

- [Robin] Thank you. Thank you.

- Of course.

- [Robin] Thanks to all the people that listen to you and work with you and make these things happen.

- Indeed, every dollar that has come through. I had a conversation with Malcolm, I think now about a month and a half ago. Malcolm does a San Fernando Valley support group fundraiser every year. I said, "Hey Malcolm, you know the Support Group Leaders Summit is having it's 25th anniversary. We are doing a fundraising campaign. Would you be willing to direct your support group, you know, fundraiser towards this?" He said, "Absolutely." And he's been on it. I'm sure all his members from the support group probably have gotten multiple hits from, you know, Malcolm already to support his fundraiser. But there are things that you can do. Yesterday, we spoke to somebody who's not able to, you know, participate in a fundraiser like this, but they allocate a significant chunk of, you know, their assets to ensure that is going towards this campaign. Every dollar matters towards what we are trying to accomplish. Last but not the least, I know I probably have surpassed my time. Dr. Joe? Team? Yeah, a lot? Okay, no worries, it's okay. Listen, if I don't speak, you're not gonna be able to do this anyways, right? So, this is important, okay? This is very, very important. At your tables, if you see, there is a QR code, okay? We are not asking you to make a gift, please. This is not a fundraiser event. But if any of you are moved by me, by what you're seeing, what you're feeling, what you're experiencing, scan that QR code, make a gift today to the IMF. We are about 1 /12 month away from hitting our fiscal year end goal. I want to be able to tell the president and CEO, "I have raised as much money as possible for the IMF," and all of your support is gonna make a huge different. There is also a QR code on your table if you want support the Support Group Leaders 25th anniversary campaign. You can also make a gift to that. The choice is yours. I always say, "At the IMF, there's something for everybody." It's like a Chinese buffet. You walk in, you can have the wonton, the noodle, the fried rice, the chicken, whatever, okay? We have research, support, advocacy, and education. You can also support any of these pillars. Whatever your passion is, whatever has changed and transformed your life where you think you want to make a difference and pay it forward, talk to any of us and we are here to partner with you. Thank you for listening.

- Good morning and I'm really excited to talk to you this morning. So we're gonna be talking about the seasons of myeloma. Now I'm from Houston, we don't really have seasons. It's either like super hot or hot. But I did grow up in Wisconsin, so obviously very familiar with the seasons. So we're just to kind of lay the groundwork, right? There's so many different treatment options. So yesterday was actually my 20th anniversary of starting at MD Anderson as a baby nurse practitioner in myeloma. And over the last 20 years it's just been absolutely amazing all the different drugs that we have now for myeloma. It's really just mind-boggling if you begin to think about all the changes that have happened. And there's drugs that we used to use that we don't even use anymore because we have so many better options now. So just to kind of talk a little bit about the different phases of stem cell transplant, there's three different phases, right? We have the beginning phase where we're, you know, making sure that you've responded to treatment. We're making sure that we have insurance approval and then during this time we're collecting stem cells, right? Then you move into the next phase where you're going to get the high dose chemotherapy. You're going to get those stem cells that we collected back and then waiting for engraftment. And during that time you may be in the hospital, you may not be, you'll be getting growth factor support and we'll just be maintain helping your body to recover from that high dose chemotherapy. And then we have the post-transplant period.

During this time it's really about helping you to get your strength back, helping you to get your appetite back. And then about, you know, three months post-transplant is when you'd begin your maintenance therapy. And then we have CAR T, right? And so I know Dr. Dispensari already talked about CAR T and kind of the process but just to kind of, you know, do a brief overview. You know, once you've been, your doctor has determined that you're a candidate for CAR T and insurance approval has been obtained, then you're gonna have those T cells collected and then they're going to be sent off for manufacturing. And during this time you may receive what we call bridging therapy. So bridging therapy is when you're on treatment to try keep the myeloma, you know at bay while we're waiting for those T cells to be manufactured. And then you'll come into the hospital, you'll receive those T-cells back and for the next 30 days you have to stay within near the CAR T-cell center. And part of that time you will most likely be in the hospital to monitor for the effects of CRS and neurotoxicity. And then about 30 days post the CAR T is when you'd be able to go back home. But during that time you're still being monitored by your local physician and you can't drive for eight weeks unfortunately. But it's a, generally speaking it's a one and done right? But in other approaches, bispecific antibody therapies. And so Dr. Dispensari also talked about the mechanism of action for that. And so we have two targets right now, right? We have got the BCMA and then which is B-cell maturation antigen and then GPRC five D. And so they work similarly where we have the bispecific antibody that's binding to a target on your T-cell called CD3 and then it's binding to the marker on the surface of the myeloma cell. And so we have two BCMA therapies, we have Teclistamab and Elranatamab and then for GPRC 5D we've got Talquetamab. And so the main side, the unique side effects with CAR T and bispecific therapies is going to be the cytokine release syndrome. And so, and it's common but it's often mild and it's manageable. We know how to manage CRS, right?

But you do need to be monitored. So we're gonna be monitoring you for fever, headache, shortness of breath, confusion, nausea and vomiting. And then we also have the neurotoxicity. And so if those of you who've had CAR T or bispecific, I'm sure you probably got really irritated by being asked the questions, where are you? What year is it, right? All these different questions, writing out this sentence to make sure that you're not having any changes in your mentation, right? Because we wanna be able to catch that early so that we can start intervention to help prevent more severe neurotoxicity effects. So now we're gonna spring into managing some side effects. So what I always tell my patients is I can't help you if I don't know what side effects you're having, right? And I find that a lot of times patients like to minimize their side effects because they're afraid of having dose reductions, right? But what we know is, is that when patients' side effects are being managed, they're able to stay on therapy longer even if we have to reduce the dose, right? And so it's really, really important that you communicate to your healthcare team 'cause we can't help you feel better if we don't know that you're feeling bad, right? Unless have a caregiver that uses like their hand signals behind your back during the doctor's visit to say that there's a problem. And so side effects of treatment can cause GI symptoms, it can cause low blood counts, it can place you at risk for infections. We can, it can place you at risk for blood clots, neuropathy, fatigue. And so we really need to know proactively.

And it's helpful if you keep a symptom diary like keeping a journal with the dates so that, 'cause sometimes there are certain side effects that are very predictable and so we can then look at that journal and kind of help to do some prevention, right? So you know I always say that if we can prevent something, that's the ideal situation. Now steroids, it's the drug that we love to hate, right? I would probably say that of all the side effects that patients experience, it's the steroids that cause the biggest problems, right? And so it can cause irritability in mood swings. And so that can be really difficult not just for the patient but also for the caregivers and family members, right? And again, we need to know if that's happening because we can't help that if we don't know that that's going on. It can cause changes in vision, cataracts, it can cause muscle weakness. And so one of the things I always tell patients, it's really important that you're getting out and doing some sort of physical activity. It can increase the blood pressure, it can cause fluid retention which can cause swelling and it can cause some insomnia, right? And so one of the things that you can do for the insomnia is I usually tell patients like once you take your steroid dose, like kind of keep track of when you start to feel the effects of the steroids. 'cause there's some patients they feel it right away. They're like okay, within an hour they're ready to go and take on the town, right?

And there are other patients that it can be delayed. And so if it, if you're one of those patients where it's delayed, sometimes you can actually take it right before bed as long as you're taking it with food because then you may allow you to get some sleep before you start getting the revved up feeling. It can cause stomach bloating, it can cause heartburn. And so again you wanna make sure that you're taking it with food. Sometimes will put you on a medication called Pepcid to help minimize that risk. It can weight gain. And I think out of all the things, another problem right is you get that famished feeling right like two o'clock in the morning munchies. And so I usually tell patients like get rid of all the junk food in the house so that you're not tempted at two in the morning. 'Cause it's probably a little bit harder to go out to the grocery store at two in the morning when you're hungry. And it can increase the blood sugar. And if you've already, if you already have diabetes, you know you're gonna need changes in your insulin or your diabetes medications. So infections can be really serious in myeloma. So particularly with some of our newer immunotherapy. So it's really important that you're doing what you can to help minimize your risk, right? So doing good hand washing is super important. Making sure that you're not around people that are sick, making sure that you're staying up to date on all of your vaccines, right?

And then also making sure that you're taking your supportive medication. So you may be on something to prevent shingles if you've gotten CAR T or bispecific you may be on some other prophylactic antibiotics. So it's really important that you're taking those. And then also if you have a fever greater than 100.4 or if you're having shaking chills to go to your local ER to your healthcare provider as directed. And we have medications that can reduce infection risk. So some of you may be on shingles pro prophylaxis with either acyclovir or Valacyclovir. You may be on prophylaxis with Levofloxacin as an antibacterial. You may be on something to help what we call PJP prophylaxis. So PJP is a certain type of pneumonia that can arise in patients who are immunocompromised. And so you may be on that after transplant and then you also may be on that if you have had CAR T or bispecific. And then making sure that you know if you've are up to date on your COVID-19 and your influenza vaccines were coming into flu season again. So you know your flu shot starts now. So if somebody asks you have you had your flu shot this year? They're talking about like from now going forward, not like since January. So, 'cause the flu vaccine comes out like August, September. And then you may be getting IVIG which is basically IGG antibodies. So it's an infusion that we give particularly in patients whose IGG level is less than 400. And then if your bacteria fighting cells, we call that your absolute neutrophil count is low, we may give you a medication called GCSF to help bring up those white cell counts. So you may be receiving that. Other side effects. So with some of our drugs, particularly with our bispecific Teclistamab, we can see some unique side effects. So it can cause dry mouth, it can cause some taste changes.

And so for the dry mouth, making sure that you're staying adequately hydrated and that you're avoiding like hot beverages but also making sure you may need, you may actually have something called thrush and that is a fungus that can go come up on your tongue and in your mouth. And then there's some dexamethasone oral solutions that can be helpful. As far as dental care, making sure you're doing good hygiene. You can also use some saliva substitute for the dry mouth, that can be helpful. And then for some patients, because they're have been dry mouth, they can have some difficulty swallowing. And so making sure, I usually tell patients like to have something to drink before you're chewing food, before you're eating something that is likely to cause some problems with swallowing. So like bread or meats or something, making sure that you've really lubricated your mouth and then because you're having the taste changes and because food isn't really tasting as well, we can see some weight loss with it. And so you can use, you know some of the supplements like Ensure or Muscle Milk, things like that can be useful. And then you may need to see a new nutritionist to kind of help you to stabilize your weight. Now we're going to move on to the GI symptoms. So diarrhea and constipation. So we can see either or in myeloma. If you look at most myeloma studies, a third of patients experience diarrhea and a third of patients experience constipation in most of the studies. And so it's always good, always good to have things on hand to manage both. And so for diarrhea we can, you know, if you're already taking laxatives you really wanna stop that but if you're on magnesium supplements that can cause diarrhea. So you'd want really wanna talk to your provider about how can we manage your magnesium level so that you're not also getting worsening diarrhea. Sometimes antibiotics can cause some diarrhea and then just the medications like Revlimid can cause diarrhea as well. And so you wanna make sure that you're taking some anti-diarrhea medication, at least have it on hand.

For Revlimid associated diarrhea we use something called Colestipol or cholestyramine to help manage that and that works really well for our patients and that has been useful. And then for constipation, you know you may be on pain medicines that can cause constipation and so making sure that you are on, you know a stool softener such as MiraLax or Senokot-S is really helpful and you wanna make sure that you're increasing your fiber intake, right? So making sure you're eating whole grains, eating fruits and vegetables, those can be really helpful. And then most importantly is making sure you're having adequate fluid intake. 'Cause if you're not drinking enough fluid, particularly water, because caffeinated coffee does not count as your fluid intake 'cause that's actually gonna be a diuretic, making sure that you're drinking like two liters of water a day. So the other side effects we can see and particularly with Talquetamab is skin and nail effects. And so you wanna make sure that you're using a good lotion. So at our center we use Vanna Cream and we actually start it before the rashes start. We do that right from when we start patients on therapy, have 'em do it twice a day, making sure that you're reporting any rashes to your healthcare team. And then you may need a steroid cream if the rash is getting worse. So making sure that if you do develop a rash that you're notifying your team. And then for nail changes that we can see, so at our center we have patients start using nail strengthener and vitamin E cuticle oil, right when they start therapy. We don't wait till the nail changes start. So that can be helpful and that may help with nail thinning but you wanna make sure that you're talking to your provider 'cause sometimes you can get like a fungal infection in your nail and so we need to make sure that that's not what's going on. And then you wanna keep your nails short and clean and then also not wearing artificial nails 'cause that's not going to be good for your nails.

And then what about pain? I would probably say that the majority of patients experience some sort of pain and that could be due to peripheral neuropathy or it could be from compression fractures or from the other myeloma lesions. And so you wanna make sure that you're one is that we're preventing pain when possible. So you know, we don't want you to get shingles because shingles can cause pain, it can cause a burning sensation even after the rash has disappeared. And so making sure you're taking those medications and then also making sure that you're, you know, taking your pain medicine appropriately, right? So we don't want your pain to get so out of hand, right? So when your pain is starting to come up to take something and not wait till it's really bad, we can also use something called scrambler therapy for neuropathy, particularly for patients who have painful neuropathy. We can use acupuncture can be helpful for pain. Sometimes we do need to have patients get radiation therapy to a lytic lesion if it's causing them a significant amount of pain. And then also physical therapy can also be helpful. Peripheral neuropathy, this occurs when there's damage to the nerves and usually it's due to some of the myeloma drugs that we use, but it also can be due to diabetes. So if you have diabetes and you're on myeloma therapy, you're kind of getting a double whammy, right? And so it can be numbness, tingling, sensitivity to touch. I usually tell my patients I don't put a lot of descriptives on it 'cause I find that if I make like if you have this, this, or this, then call me then if they experience their neuropathy something different then they don't call. So you know, you know what your hands and feet feel like and if that changes then call your healthcare team so that they can better assess if you're beginning to have, having neuropathy. And so as far as prevention, so now we use Botensilimab subq. So when I first started we gave it IV. Now we use subq because there's less neuropathy with it.

There can, you can use vitamin B complex vitamins to help minimize that. But if you do have neuropathy, you wanna make sure that your home environment is safe. So because you could easily trip because your ability to feel the floor underneath you is going to be impacted. And so you wanna get rid of like throw rugs, things like that so that you don't trip on that. And then the other important thing is, is it may impact your ability to sense temperature. And so if you're going to get into the bathtub or the shower, you can't sense temperature with your hands and so now you're trying to test the temperature and you don't even realize it's hot, right? Because you can't sense it. And so using like if your elbow kind of like when you have, you know, babies and you, you know, they tell you like when you're gonna test the water in the bathtub to use your elbow and not your hands, same kind of thing. 'Cause you wanna make sure that you don't burn yourself. If you do have neuropathy, again, make sure that you're letting your team know or if it's worsening. And then sometimes we can do physical therapy to help with the balance problems that come because of the neuropathy. We can see changes to kidney function as a result of the myeloma. And so we wanna make sure that you know how to, you know, prevent further damage. So you don't wanna receive any CT contrast if you have impaired kidney function because that can actually make it worse.

You wanna stay hydrated. So again, drinking water, I always have feel like I have to sometimes tell patients like, but don't go crazy 'cause I've like had patients like when they turn in a 24 hour urine, they turn in like five liters of urine and I'm like okay well we could probably cut back on the fluid and take a little bit, maybe like two liters a day. We don't have to go too crazy so, you know, we don't want you over hydrating 'cause then that can cause like other problems. And then sometimes we have to dose reduce your medications for your kidney function. But most importantly if the kidney function is up due to your myeloma, we need to treat your myeloma and we need to be aggressive with treating your myeloma at that time. And then sometimes some patients do require dialysis because their kidney function is to the point that now the potassium is becoming too high or the phosphorus is becoming too high. And so in those cases we do sometimes have to do dialysis. Other supportive care that you may, medications that you may be on. So we wanna prevent blood clots so when we combine certain medications together, it can place you at risk for a clot. And the biggest thing with those clots is we don't want the clot to go to your lung 'cause that can be life threatening. So you may be on blood thinners such as aspirin or a medication called Eliquis or Xarelto. You can use compression stockings. But what's really important is activity. You wanna be active, you wanna be up moving around because the more immobile you are, the more that places you at risk for a blood clot. You may be on medications for your bone health such as the bone strengthening medications, you'll likely be on calcium, vitamin D. And then physical therapy. And again, what's important for bone health, we all know this, particularly us women who get osteoporosis as we get older, right, is going to be weight bearing activities, right? So don't forget about your arms, like everybody seems to focus on the legs, but don't forget about your arms and you don't have to lift a lot of weight. Like five, 10 pounds is really all you need to help, help with your bone density. Then for fatigue, the biggest thing with fatigue is we wanna make sure that you aren't experiencing depression.

You know, when you're diagnosed with myeloma it feels like you're being hit by a freight train, right? Like it just came out of left field and it really threw your whole life for a loop. And one of the main, one of the main symptoms of depression is fatigue. And so we really wanna make sure that that's not causing it. Sometimes we do do blood transfusions and then again, the biggest thing that you can do for fatigue is activity. There's a theme going on. And then for anxiety, you know, we put you on steroids, right? And the steroids can make you feel anxious in and of itself, let alone dealing with the uncertainty of having myeloma also can increase your anxiety. And so sometimes, you know, you can do some relaxation or meditation, going for counseling, but sometimes honestly we just have to, you know, you have to go on a medication to help with it and that's okay. You know, one thing I like to reiterate to patients is if I told you that steroids was increasing your glucose level, you would not tell your provider that you were just going to get your mind to overcome the glucose not going up, right? You wouldn't do that. But what do we do with anxiety and depression? I'm just going to think myself into a better place with my mind and I'm gonna overcome my depression in and my anxiety, right? And sometimes that's just not possible because one, we are giving you a medication that makes you feel that way, right? And so there shouldn't be any shame if you need to go on an antidepressant or an anti-anxiety to help you get through that. So we talked about fatigue. So we're gonna be looking, are you anemic? Are you having pain, is it from treatment? And what can we do to help minimize that. Anxiety is, occurs in over 35% of patients and depression is at least a quarter. I'd probably actually say it's probably actually more. And so don't let your fear of people judging you get in the way of asking for help. You know, in our society there's a stigma. Somehow we separate our brain from the rest of our bodies, but that's just not the case. Care partners are vital for success. And so they can help with managing medications, they can help with physical assistance, they can help with knowledge of myeloma because they may be able to, when they're listening to you during the appointment, they may be picking up on things, they can help with financial decisions and they can just be your advocate, right?

And so there, it's so important and it doesn't just have to be any one person. My cousin was diagnosed with ovarian cancer last year and she, she's single, and she has this whole network of her friends that she kind of collected and they were called Kirsten's Angels. And they were just different people that she could call on to help with appointments and help her bring, get groceries and things like that when she was having a bad day. So it doesn't just have to be one person, it can be a group of people to help take care of you. And it's also important that caregivers take care of themselves. Caregiving is really tough, it's stressful and it's important that as a caregiver, that you're taking care of your own health as well. Making sure that you're staying up to date and seeing your doctors and getting your cancer screening, testing done. And so it's just really, really vital that you take care of yourself.

And the IMF has resources to help care partners. And as I had mentioned, you know, you can cultivate a care network and so you know, we know that increased longevity, it improves adherence. There's lower risk of cardiovascular disease, there's improved mood, it reduces stress. And so making sure that you're making those connections with your friends and your family is really, really vital. You know, even joining a support group can be helpful. And so my, just my last few slides, so making sure that you're seeing your primary care doctor and getting your recommended health screening. So making sure you're up to date on your blood pressure, diabetes, colonoscopy, mammogram, prostate, getting your vision and hearing checked. Those are all really, really important. Making sure that you're getting regular activity, that you quit smoking if you smoke, and that you get sufficient amount of sleep. And so sleep is really important. We know that disturbed sleep can cause increased heart related death, it increases anxiety and there's lots of things that can interfere, particularly steroids. And then if there's a lot of fear, anxiety, and stress and so things to avoid before you go to bed. Caffeine, nicotine, you know, not eating large meals and then computer screen time, although I have to say like I am so guilty of that and then I'm like, why can't I sleep? And sometimes you may need a sleep aid and there's a lot of resources out there for you as patients as far as helping you to understand your treatment, understanding the side effects with treatment, and then also what you can do to help manage your side effects and just know that you are not alone. That's it.

- Awesome, thank you, Theresa, thank you Tiffany, for a fantastic talk. I know you're probably a little tired. You've been sitting a lot today. This is gonna be a brief lecture, and then we're off to lunch. So I don't wanna keep you from lunch too long. However, this is obviously a critical topic. We've raised it a few times over the course of the last day or two, but I do want to dive in just a little bit deeper to talk about health disparities as we've described them here. Now, whenever I use these words, people, some people get uncomfortable, and that's okay, because these are topics that people have often said, "It lands in the three Ps." People can look at this topic as being personal, professional, or political. Let's take the political part out, not that there's any politics going on in the country or anything at this point. Yeah, awkward, party of one. Anyway, we'll take the politics part out of it, and think of it as both a personal and professional phenomenon. And so when we talk about health disparities, I tend to like the CDC definition.

There are different ways we define this concept, but I'll read this to you. But they're "Preventable differences" "in the burden of disease, injury, violence, "or opportunities to achieve," notice the word "'optimal' health that are experienced" "by socially disadvantaged populations". So lots to sort of unpack there. But the key words are that they are preventable, that we want to have people achieve their optimal health. And this is experienced by socially disadvantaged populations. So it's not that there's some perfect standard of health that we want everybody to achieve, it's their individual optimal health. A little bit like yesterday when someone asked me "What's the standard of care in myeloma?" It's hard to say. Is it a triplet? Is it quadruplet? I mean, it really depends on a lot of scenarios and similarly, when we think of health disparities. And so that's the disparity. We overcome it by seeking health equity. What is equity about? Well, it generally refers to individuals, again, achieving their highest level of health through the elimination of those disparities in health and in healthcare. And so, I can argue, I'm giving a talk in a few weeks in Charlotte to a group of physicians.

There's an organization of physicians in Charlotte, that was created actually 90 years ago, actually, when Black physicians were not welcome in the usual organizations in society, which is a terrible mark on our history nonetheless. But, and the title of my talk is "Multiple Myeloma, the Most Disparate Cancer" "in the African American community." And how can I use that word? I use that word because we look at all the different cancers, there's different disparities in different ways, but a Black man or a Black woman diagnosed with myeloma today is expected to live half as long as the exact same aged white man or white woman with myeloma. And hopefully we would all agree that's totally unacceptable. Now, that's not all myeloma related. There are other things that influence mortality, but that is clearly unacceptable. And that's more dramatic in myeloma than any other cancer, specifically within the African American community. I'm gonna be focusing a lot of our discussion within the African American community, because that's where we see the greatest disparity. But we see disparities in other places as well, within the Latino American community. There are disparities based on age, based on gender, based on geography, based on orientation. There's a lot of different ways that we can cut the disparity concept, but I'm gonna be focusing primarily within the African American and Latino American population, because that's where we see the greatest disparity. I was, I quote my daughter when I asked her when things became so much more aware within the society with the Black Lives Matter movement, I said, "Honey, how do you deal with someone who says" "to you, you know, 'Black lives matter', "don't all lives matter?" And she says, "Well, of course all lives matter." She says, "All the houses on our street matter," "but when one of them is on fire," "we need to do something about it right away." And so we have lots of houses, sadly, on fire within the myeloma disparities world.

But there are a few that are particularly lit up that we want to address. So what has caused this? And again, I'm not gonna give you a long talk on drivers of disparities, but I always start with these top three, because if we don't look at these top three, and we just dive into the myeloma specific ones, we lose the bigger picture that there are issues within racism within the healthcare system, the key social determinants of health. You know, Theresa shared with us this great talk yesterday on shared decision making. It's hard for me to have a conversation about my patient, about whether or not they want a triplet or a quadruplet, or they want a transplant or not, or a clinical trial or not, if they're hungry, right? If they don't have the basics of life, right? And we're spoiled here in many respects when we have these patient-family seminars in cities where people tend to have opportunity.

But we host a lot of these meetings and there's a strong purpose about the way we feed you this weekend. Not just 'cause we love to eat, but because we know that there are people that come to these seminars where this is gonna be the only three-course meal that they're gonna get in the course of that week. And we wanna make sure people are fed. So our health is very much influenced by our housing, by our food, by the security that we have in those areas. People who live in, in what we often think of as grocery deserts, or food deserts, where people don't have the opportunity even to get the kinds of groceries that you and I take for granted when we go, I know my wife thinks I'm addicted to Costco, and addicted to the grocery store 'cause I like to buy my own fruits and vegetables before I cook them. And we do like grocery shopping. A lot of people just don't have that opportunity. And so those things always have to be encoded in our thinking of why there is a disparity. But now I'm gonna drill down a little bit into the myeloma specific ones. There are things that are specific to myeloma that drive these disparities. The biology of myeloma, and again, I'm not gonna nerd out or geek out on you as I promised earlier, but as we've said so many times this weekend, myeloma is different in every person.

But we've generally divided people into high risk and standard risk myeloma. When someone hears my opening statement about the difference in survival between Black patients and white patients, for example, they might say, "Well, perhaps it's a little bit like prostate cancer" "or some other diseases where Black patients" "are more likely to have a more aggressive form of myeloma." That's actually the opposite in myeloma, Black patients are actually less likely to have high risk disease. They're more likely to have translocation 11:14, which of which there was some discussion earlier, which is generally a favorable prognosis. So it's, we can't blame it on biology, but there are so-called concomitant diseases that confuse the picture. Myeloma, when it comes to myeloma, for example, I always say that diabetes is a great challenge, 'cause diabetes is the great mimic, right? We have a lot of our patients eventually diagnosed with myeloma, who for many years have been told, or many months, have been told, "Oh, your anemia, your proteinuria," "your renal insufficiency, your neuropathy", "it's all from your diabetes", when in fact, they're brewing myeloma the whole time. And so often, the diagnosis delay, which is driver number five, is delayed because of that. That's why I remember I mentioned yesterday, the average patient sees their primary care provider three times with signs and symptoms consistent with myeloma before the diagnosis is sought after. And many of you have already shared unfortunate stories with me since yesterday about the delay in diagnosis that there was.

That delay is average three to six months longer if you're African American or Latino American. And some of that has to do with diabetes. Some of that has to do with lots of other access to healthcare reasons and diagnostic reasons. But that becomes a big part of the disparity. Something that we really want to focus on. And so for example, as I'll share with you what we're doing with our M-Power program, we're about to launch a program in inner city Detroit in diabetes clinics where we're gonna start to more vigilantly look for myeloma because we think myeloma has been underdiagnosed in that population. So the delay in diagnosis is important. And then I often call the access to the key therapies that have changed myeloma, you know, Dr. Lonial and I shared earlier our future look at myeloma. If I look back at the last 20 years of myeloma, and we have some myeloma doctors here, of course, that have been doing it, doing myeloma for a long time, I would suggest that there have been four major movements that have significantly improved survival in myeloma. And they all start with the letter T, which makes it easier for me to remember, triplets or three drug combinations, now moving towards quadruplets, as we've said, transplants or autologous stem cell transplants, clinical trials as Yelak and I shared yesterday. And then most recently, CAR T-cell therapy. Sadly, we've shown for all four of those, there are certain populations, socially disadvantaged populations based on our definition, who have had less access to these four things.

And so it's no wonder that their survival and the outcome has been reduced. And then lastly, number seven, put it on us as the providers that we don't always reflect the cultural sensitivity and competence that we should. We may not be sensitive to these kinds of things. We may not be aware when I'm in clinic that there's a lot more to someone than just their plasma cells. As we've said so many times, we don't treat myeloma, we treat people. And so us being as healthcare providers and teams more aware of these and more willing to support people through this journey is really important. And so we'll share with you a little bit about what we've been trying to do to help overcome that. So the fast facts are here. I can go into a lot of detail around them, I won't, most of this has come out over the last day, but there's a longer time to diagnosis. Their African American and Latino American patients are diagnosed at a younger age, which is also part of the delay. 'cause you know, medical school, when I went to medical school, you're kind of told that myeloma is a geriatric condition, right? Little do we know that it can happen in much younger. I traveled once to Uruguay to visit what we think is probably the youngest person ever diagnosed with myeloma, it was an 8-year-old boy. You know, poor pediatricians don't know how to spell myeloma, right? They don't treat myeloma. So that's extremely rare, of course.

But we do see a huge age range of myeloma, and we all have patients in our practice in their twenties, in their thirties. But on average it's diagnosed younger. We've already mentioned already, it's twice as common, less access to the four Ts, more likely to have lower risk features as opposed to high risk features, like P53 deletion. And that the survival outcome, as we said, is half. But number seven here is particularly important to me, because it proves to us that we can do better. So when we look at the VA system, and albeit not a perfect system, at least theoretically in the VA system, independent of your race or ethnicity, you have the same access to the diagnostic and therapeutic pathway of care. So when we look at studies within the VA system, it's ironic that African American patients actually do just as well, if not better, than white patients. So it tells us that when given equal access to diagnosis and therapy, we can have an equitable outcome. But obviously that's not what we experienced in society at large. So what did the IMF do? Well, we've created this program, Sylvia made mention of it. It's come up a few times today, of what we call M-Power. It's a bit of a play on words, M standing for myeloma, power, we're wanting to empower patients and communities to change the course of myeloma. That what I've shared with you up until now, hopefully you have a bit of discomfort in your stomach saying, "This is not acceptable," independent of what race or ethnicity you may have yourself, that this is not acceptable. I don't think it's fair for people to have such inferior outcomes with myeloma. And so we want to reverse that, and we want to improve the short term and long term outcomes of African American patients and all patients with myeloma. Going back to the burning house analogy, we're committed to every patient.

The I in the IMF, as I said yesterday, was international. We want to help every patient in the world, but there's clearly disadvantaged groups. And so we did this based on this three pillar model. So we have three major aspects of our work. Number one is to engage the community, partly what we're doing here, but we'll show event events and things that we're doing where we go right into the community. We're trying, I know I sound so simple when I say this, but trying to break the way of thinking that we've always had, that I only interact with the healthcare system when I'm sick, right? I'm sick, and I go to the hospital, or to the clinic, or to whatever. I'm trying to have us as a healthcare system realize that we need to proactively be in the community to promote health, to engage the community, to build that kind of trust, so that when that person is sick, and they do have to come in, there's already a relationship built. It's not always a one way street coming into the clinic. And so we believe community engagement's important, as I'll show you, we'll engage with everybody and anybody in the community. We do programs in churches, fraternities, sororities, community health centers, you name it. We'll work with anybody and everybody. We've worked with the National Medical Association, with the Black Nurses Association. We work with anybody to embed ourselves into the community, do projects, do seminars.

Dr. Shah was with us, just a couple weeks ago, I'll show a picture where we did a program around Juneteenth in Harlem at the Abyssinian Baptist Church. And she gave a talk on nutrition. It really wasn't even really about myeloma. I gave a talk about blood. I talked about sickle cell disease, and just what blood means within the Black community. And of course, we talked about myeloma and Yelak shared his story as a myeloma patient, just so that we can build that trust and raise awareness of myeloma in general. Part two is educate. If the delayed diagnosis is a big problem, we want to educate the primary care physicians. 'cause by the time you see Dr. Joe, or Dr. Shah or Dr. Fonseca or Dr. Dispenzieri, I mean the diagnosis has already been thought of and already been worked up, but it's at the level of the primary care that we want to help primary care doctors know when to think about myeloma, and what tests to order, so that they can facilitate that diagnosis more quickly for all patients, but in particular those patients that are at higher risk of delayed diagnosis. And then lastly, to enhance the care of the patient who is being treated for multiple myeloma. So that's affecting the whole healthcare team and their cultural sensitivity and competence affecting the access that patients have to care and facilitating that. So all the projects, everything that we've done, whether it's, as I've mentioned, engaging in a community or educating a primary care doctor, or enhancing the care, they're all under the umbrella of our M-Power movement.

And M-Power has been both local and national. We recognize that no two communities are the same. And we don't just do a cookie cutter approach in saying, "Oh, Baltimore is the same as Atlanta," "which is the same as Detroit," "which is the same as Charlotte." We recognize that every community is different. And so we go in, and we build connections within the community, and do programs that are specific to that community, but also provide resources nationally. So to give you a flavor, we've gone to different cities, as you can see here, like Charlotte and New York and Tampa and Detroit over the last couple of years. We do Facebook Live programs, sorry, my face is everywhere here. But we do programs where we try to connect with people in different ways, who have access to the internet. We have to do programs to remember that there's some people that don't have access to the internet, or may only have it through a phone. And making sure that we do it in a manner that's comfortable for them. We've done a lot work, as I've mentioned, with educating primary care doctors, creating these little pamphlets that simplify what are the signs and symptoms to look for and what are the key tests to order. Doing programs, we just did a program a couple of weeks ago, or last week at the annual meeting of the National Medical Association, which many of you may be familiar with, historically known as the Black Doctors Association, they hold an annual meeting. And we did a program directed towards primary care, and those who are on the front lines, to be able to diagnose it more quickly.

We've also tried to affect the scientific and medical community, as geeks and nerds as we are, we read papers all the time. And so we wanna be able to have publications that will allow people to understand, in the physician community, and the nursing community, to understand it better. One of my favorite programs as I come almost towards the end here, to share with you, is a program that we've done with medical students called The Medical Student Scholars for Health Equity in Myeloma. So what we've done is we've reached out to medical students, most of them from historical Black colleges and universities. So places like Meharry and Morehouse and Howard. And we've paired these students, and you might recognize some of the pictures of the doctors next to them, we've paired these students for six months to do a project in health disparities related to myeloma. So we've given them the opportunity to cover any topic that they wish within that umbrella so that they can get experience in doing research. For most of these students, it's the first research project they've ever done. But it's an opportunity for them to learn about myeloma, to learn about health disparities. Of course, I want all 12 of them every year to become myeloma doctors, but whatever they become, we want them to be sensitized to myeloma, if they become a primary care doctor, or a cardiologist, or a surgeon, or whatever else. And at the end of the six months, we bring everybody together, and we just did this last week. This is some pictures from last year. 'cause it was so hot off the press. But we brought everybody together at the National Medical Association annual meeting and each student presented their project as a poster. And we had a poster walk, beautifully last year. We had a whole series of people joining us in the poster walk. Some of you may may recognize a dear woman there, Dr. Edith Mitchell, who is on our board, who sadly passed away this year. Just an incredible woman, and pioneer in the field of health disparities. But these students were unbelievable. I mean, just speaking from the posters that were presented,

Dr. Shah was with us last week in New York City. It was just overwhelming what these students were able to do in such a short period of time. And so we hope no matter what field, as I mentioned, these students go into that they're always gonna be sensitized to it. So we've tried to provide resources, and Peter's here, from our marketing team, he's been so helpful to us in building a website and creating resources for people to help them in multiple different ways and understand how myeloma affects their community with tremendous social outreach. And going out into the future with our engage, educate, and enhance. We're going out to multiple other cities, and actually going out in 2025, we're gonna start to create programs within the Latino American community with our first planned in Miami next year, and the region there. So just to leave you another picture, this was the program we did just a couple of weeks ago at the Abyssinian Church in Harlem. It was such a privilege to be there and to engage with this community. I even brought my two daughters with me who had a chance to learn a little bit more about what Padre does. So what do I leave you as some takeaways today? You know, health disparities really are prevalent across all diseases, but particularly as we've mentioned, most disparate in multiple myeloma, there are other types of inequity, there's no doubt. But I focus today within the African American community where the disparity is the greatest.

And it's hopefully giving you a sense of the bigger picture here, also of what the IMF is trying to do, and hopefully engage you to do this. If you want to be involved with us, we have a special little table even out in the foyer here that you can come and see. Joy who works with us, Joy Tisdale is my partner in crime and M-Power. We even have a little bit of M-Power merch, I think there may be some fanny packs or hats, or if not, we can order one for you. But we want you to be aware of the program, and what we're trying to do to reduce these inequities. And going forward, What can you do? You know, hopefully be more aware of this, that just listening to what I've said over the last 15, 20 minutes will sensitize you to the issue. And we think of the opportunities, and support the M-Power movement in whichever way you want. You can go to the M-Power website, read more about it, learn more about what we're doing, especially if we're coming to a community near you. We would love to have you engage with us as we go forward.

- Such an honor to be here. And thank you all for sticking around to listen to this talk. I wanted to ask you all a question. How many of you think you get enough fiber in your diet on a daily basis? Maybe raise your hand. So we've got like, sounds like 50% there, but have you heard of the fiber gap? Anybody? You might have heard me talk about it previously. You have there? Yeah, so,. In the US 60 people were surveyed and asked like, do you get enough fiber? And 67% of the US population said, I get enough fiber in my diet. And that's what they thought. But in reality, how many do you think actually got enough fiber? 10 is too generous. It's five. Less than five actually. So the next 30 minutes I'm gonna talk about how fiber is your friend and why it is your friend and like how you can think about it and where to get enough of it in your diet. So we'll talk about diet, we'll talk about a microbiome, the research we're doing in that, and then some practical tips to wrap it up.

I wanna make a disclaimer in the beginning that of course when we are talking about this, it is a generalization of what we're talking about and you need to individualize it to yourself. You have to think about whether you're diagnosed, newly diagnosed, relapsed, whether this is right for you at this time. Whether you feel receptive to hearing about it or it's too much and whether it empowers you or overwhelms you. Of course these issues are important, but there are right times for them and you can decide for yourself. I also think some people like to make changes overnight and they say like, okay, I'm gonna cut out these things, I'm gonna make changes overnight. And other people might wanna do this gradually and say I'm making one change at a time. So it's not overwhelming. So think about what floats your boat pretty much. So nutrition research I think is a really unmet need for patients. And part of it is me, I had Hodgkin's lymphoma about eight years ago and when I went through that experience, while I was a fellow, I realized like I got no training in medical school in residency or fellowship around this topic. And I realized like I have family members, friends , trying to tell me, oh, eat this, do that. And then I realized this is something that's very important and we need to bring more evidence into this area and talk about it more for patients. So that's what I decided to focus on in my career as a faculty.

So what is a balanced diet and who follows this? And the reason I recently started talking about this, is because I sometimes get pushback and people say, you shouldn't be telling patients what to eat. Cancer patients are already going through enough. Just tell them, eat a balanced diet. And my answer to you is, how many people here know what a balanced diet is? And that's the thing which even I think many physicians are not aware. So when we say eat a balanced diet, what does that really mean? And like how do we even follow it? So if we think about the US population, how many of the US population are even following a balanced diet? So these are the USDA guidelines. Some of them, of course, they're more, but I'm just focusing on these, fruit intake, vegetable intake, fiber. And then the healthy eating index, meaning a score of, ideal score is a hundred, but what is the US population's general scores? And this is basically the US population. Fruit intake only 12% meet it, vegetables 10%, fiber less than 5%. And these guidelines, less than 20% meet them. So when we do say, and getting a score of 59 out of a hundred on a a healthy eating index is like a fail. So it's a low score. So what that's the average for the US diet. So this is just the USDA guidelines. We're not talking about any specific diet, any special diet, we're just talking about the USDA guidelines here. And very few people even follow those.

So when we say balanced diet, I think it just confuses everybody. It's like, what does that mean? And so I think you can go to look at some of these things, but we'll talk a little more about why it's important. Another thing people will say is like, we don't have enough evidence that diet affects cancer directly, but we have enough evidence that it affects cancer indirectly. And that's what I wanna show you here. So this is a patient who I treated some years ago and you can see the number of medical problems in addition to myeloma that they had. And so I, because of this, it makes it harder for us to take care of the patient. And for that reason, the patient was not a candidate for stem cell transplantation, CAR-T cell therapy clinical trials and even some intensive chemotherapy. And because of that they had a decreased overall survival. What I've highlighted in green are things that I believe could have been avoided over a lifetime with diet and lifestyle changes over time. Of course, you may argue, some of the things you may not agree with, but it is potentially possible. So I think that whether directly or indirectly it affects it, this is something we wanna think about. How do we optimize ourselves to be able to handle all the treatments that we want to go through in the best possible shape. Now moving to some of the studies that have been done around diet and cancer. And the thing is that dietary research is hard, partly because it's not like a drug, you either take it or you don't take it. It's subjective, right? Like some people might follow it 50%, some might follow it a hundred percent. And looking at populations, that's one good way to study it in terms of understanding.

But the problem with that is you can have a interactions where somebody may have also be walking and physical activity. So is it really the diet or is it because of their lifestyle for other things? So there are these issues that come up, but most studies try to adjust for these issues when they do the analysis. You can see three studies from different countries. All three of them show that people who ate more plants had less cancer by about 15 to 20%. Very consistent findings. Whichever way you analyze the data. In myeloma, there have been a few studies looking at this specifically. And you can see here one study from the UK, this had very few number of myeloma patients, 65, because myeloma is rare, but the population was huge, 60,000 plus. And again vegans, vegetarians had a lower risk of myeloma than meat eaters, in this study In the nurse health professional study, patients who had a, people who had a higher inflammatory diet had a higher risk of myeloma. We published in the last year looking at two data sets. One is the NIGRP and this is the largest to date looking at population. And those who ate more plant foods had less myeloma compared to those who didn't. And the same thing we looked at in the enhanced study. And in this study we basically looked for MGUS, the precursor to myeloma. And those who had more sugary drinks and whether it was artificially sweetened or naturally sweetened had a higher risk of like 40 to 60% increase odds of MGUS and those who were eating fruits, vegetable whole grains had a 40 to 60% lower risk of MGUS. Again, these are population studies. There are the issues around adjustment that we have to take into consideration, but if all studies are consistently showing us the same thing, there must be something there that we need to look into further is how I see it.

Dietary mechanisms for cancer risk reduction. So we published on this in terms of like how do plant foods reduce risk of cancer and then multiple mechanisms through the fiber when fiber leads to anti-inflammatory effects, phytochemicals or flavonoids, which are basically plant chemicals that have those effects too. And then optimizing weight, insulin resistance, insulin like growth factor, the microbiome inflammation. And then also these are different mechanisms. So we'll talk a little bit about each of those. And I'm not sure how many of you know about these guidelines, but these are guidelines from the World Cancer Research Fund and also the American Institute of Cancer Research. When we surveyed patients less than a third knew about them. So really we're not doing a good job educating patients about it. But you can see out of these cancer prevention recommendations, six out of 10 are related to nutrition and diet and these recommendations are based on thousands of articles. So there's an expert panel that puts together not just myeloma, but all cancers and all the dietary information and says what are the common themes we're seeing between all of this dietary research and puts it together. And you can see that eating a diet rich in whole grains, vegetable fruits and beans is really very center here as well. And consistent with what we're seeing. Other things is limit consumption of red and processed meats, sugary foods and then alcohol and fast food and processed foods, of course. So now let's talk a little bit about the microbiome. And I know that can sometimes be a little more exciting. And I think this is a topic that you're gonna see a lot more in the decades to come.

We had genomics. Than we had immune therapies. And then I think the next frontier is microbiome, is what you're gonna see a lot more of over the next decade. And do we have more human or bacterial cells in our body? Because I'm asking. Or because it's true. Both ways. But basically we have about 30 trillion human cells and 38 trillion bacterial cells in us. So we are more bacteria than human. It's just that the bacterial cells are small so you don't see them and you see your human form, but you actually have more bacteria on you than human cells. And it is important because of this. We have to think about what the bacteria want to eat, not just what we want to eat. And that's what why fiber is what's important here. So the microbiome in health and disease. When we think about microbiome for health and disease, when there's dysbiosis, there's going to be inflammation and that inflammation can be more systemic too when microbiome is perturbed. And there is data on how the microbiome is central to disease and health in many different ways. And one concept I wanna bring up, is the concept of microbiome diversity. So I'm not sure if you've heard about this before, but think about a rainforest versus a plantation. The rainforest obviously has many more species of bacteria, insects, animals, all of that, and even plants. But the plantation will have only one type of plant and maybe not that many different species. So what you really want is a rainforest of a microbiome and that is called gut microbiome diversity. When there is this diversity of it.

And within the microbiome space, there's a lot of debate on which bacteria are important or not. And I think we are just scratching the surface and it is very difficult to know exactly and that's a lot of research going into it. But one consistent theme in cancer that pops up and you can see, is that microbiome diversity is associated with survival. And this whether, whichever cancer you look at, you see the same theme pop up and it's like anytime you read a microbiome paper, this is one of the things you'll see. And so this was from colleagues at MSK looking at transplant patients and you can see that patients who had higher diversity, actually had a longer survival post-transplant. I'm sure the next question you'll ask me is how do we get a more diverse microbiome? And we can talk about many different things, but one of the things in terms of gut microbiome diversity was looking at a study which looked at over thousands of individuals who are healthy and asked them to like fill out a dietary survey and said based on their diets, who had more diversity versus less. And those who ate more plant foods, those who ate more than 30 plant foods per week compared to those who ate less than 10 plant foods, actually had more diversity and better microbiome health overall. But how do we define those 30 plant foods? Is it eating broccoli 30 times in a week? And I'm talking about 30 variety of plant foods each week. How they defined it was if you're eating carrots, potatoes and onions that counts as three different plants. So if you make a soup with all of those or you you're eating a stew with it, you're getting three or four in that. So having the variety in what you eat is important in going out of the comfort zone because each different food feeds different bacteria. Moving on to metabolic disorders like obesity and diabetes. There have been very clearly linked to an increased risk of cancer. And for obesity, it is 13 different cancers that have been linked and myeloma is one of them. Diabetes, the data is a little bit less and for myeloma it's not as strong, but there is a link with diabetes and outcomes. We published recently looking at that with Mount Sinai and we saw that patients who have diabetes have worse outcomes than patients who don't.

And that's probably because the diabetes leads to the insulin resistance, inflammation and the steroids and the difficulty handling treatments. So I think if it's important to try to think about these diseases as things that we can manage or bring under control. It doesn't have to be that you have to have diabetes or elevated BMI or things. These are things that can be over time taken care of. I know that it's not easy for everybody and I'm not saying that that is, but I'm saying things that we could maybe think about, how do we approach it and focus on them as well. Now moving to thinking about in the prevention space and some of the research we have done is we looked at thinking about like pre-cancer states of monoclonal, gammopathy to myeloma, smoldering myeloma and then myeloma. We know that progressive genomic alterations, so genetic mutations, increase the risk and as the disease progresses, there are more genetic changes, but we know there's also more immune dysfunction as the disease progresses. So it's a balance between the genes and the immune system that really keeps the cancer in check. And there are things, the modifiable risk factors, that affect the immune system that maybe could put, alter this risk of progression. That's kind of what we're trying to study and see with our new intervention trials and we'll show you some of that data next. So we do know, and like I said about elevated BMI and myeloma risk, patients who have an elevated BMI and MGUS, were twice as likely to progress to myeloma than if they had a normal weight, suggesting that there may be a link to the inflammation or things like that that may be increasing the risk. And this was not just in one study, it was in three studies. I'm showing you two here with consistent findings. So with that, we started the new intervention trial and this was something I started about almost five years ago, the concept. And then we opened it to enrollment in 2021.

The study finished in '22, 23 was when the patients all finished on the study. But what we did in the study was we enrolled patients with MGUS or smoldering myeloma. So the precancer state, we gave them three months of a really high fiber plant-based diet and six months of coaching, followed them for a year. We shipped them lunch and dinner for three months and provided guidance with a dietician as well. And I'm just showing you the results from that. But we were able to see that we improved dietary adherence and quality of the diet. So you can see that to unprocessed plant foods, the dietary intake was about 20% before they went into the study. It was 92% on the study and even one year out from the study, once we stopped giving them the food, it was still 60%. So really much higher than where they started out suggesting that once people make these changes, see the benefits, it's possible to keep it going. We also saw an improvement in weight. Of course these were patients with an elevated BMI, so it was about 7% reduction and this maintained at a year out too. Quality of life improved too for patients. So they felt better on it as well. You can see here patients, things that improved for patients or how they felt in green. You can see different things that subjectively patients reported they felt better with in terms of weight, hypertension, even sleep, energy. We had a few, one patient who was able to stop insulin.

One patient stopped medication for potassium, one stopped an antidepressant. So we were able to see some patients come off medications too. And all patients felt like this was something they could do and some patients saved money because they were able to stop medications too. Other things. So we talked about insulin resistance, that is a state in diabetes, but also it can be present without diabetes too, where insulin levels would be a little higher in pre-diabetes or things like that. We did see that insulin levels came down in these patients. The microbiome diversity that we talked about improved and it remained improved even at one year out. So we were able to see that improvement and maintain it. Also, we looked at inflammation. There were only seven patients who had an elevated inflammation marker, c-reactive protein. But that came down and with about half at the end of the study compared to where they started. Cholesterol dropped by about 20 points. And we saw changes in the immune system too. In the interest of time, I'm not gonna go into details, but it was more like an anti-inflammatory or acquired an immune system.

There were two patients on this study whose m spike was rising before they went on the study. So from 2016 to 2021 or so, their disease, as you can see in the blue lines, were two different patients whose disease was rising. So it had increased for one patient from .2 to 1.2. The M spike. And then on the study, it slowed down and the these are two which were statistically significant. So I'm showing you other patients may have had very small proteins, so it's hard to see a change or it may have been very stable disease. So we're not able to see a change. But these two patients that had rising disease, we were able to see a change. It's also important to know there were a few patients who didn't lose as much weight, didn't follow the diet as well, and their disease continued. It did not change and it was rising as well through the study. So I think that, again, this is a very small study. This is very preliminary data, but it is encouraging to see that there is some ability to maybe potentially modify it. This was one of the patients on the study. Before the study, this is him and this is after. And he says that for him this was like, he was on insulin for 30 years before he went on the study. He was able to come off insulin and he's not needed it for few years after now. And so it's helped him basically live a more active life. He's in his seventies, you might think that he's younger, but in his seventies and able to do all of this. So it's never too late to think about these things. We also did a study in mice to look at can a high fiber diet delay progression in mice. So mice studies are very controlled and they allow us to look at one variable only and not anything else. So we gave half the mice and this was in collaboration with Dr. Matteo Bellone in Italy. So his lab conducted these experiments, but we give half the mice a controlled diet, meaning standard mouse diet and we give half of them high fiber diet, meaning this was not like a a western diet or anything like that. It was standard mouse diet versus high fiber mouse diet. And you can see that the number of mice that progressed, in the standard diet, all the mice progressed to myeloma In the high fiber diet, half of the mice had not yet progressed at the end of the experiment. So with that, we are doing other studies.

This is a decentralized study meaning you can be in any state in the US and participate. In this study, a patient has to have smoldering myeloma. It's a very short study. We are trying to understand the microbiome in smoldering myeloma patients and it's a two week study looking at different supplements and diet and patients would get randomized. This is through the Health Tree Foundation. If you're interested in this study and you have smoldering myeloma, you can come talk to me after, but also you can sign up through their website. The intervention Tree trial. This is a trial similar to the pilot study you saw. This study is enrolling at MSK but also opening at Emory within the next week. And with this study patients have to have MGUS or smoldering myeloma. So the precursor states and we're looking at diet and supplements like curcumin and Omega-3 and the effects on the microbiome and myeloma progression. Patients. We've had some patients fly in from other states too. If a patient is interested, they have to be able to come to New York, or now Emory, five times over the course of a year spread out. So if that's something that people are willing to travel, then that is potentially they can enroll because the intervention, the diet and all of that will be done locally. We don't have enough data in terms of whether diet can affect treatment outcomes at the same time as when you're getting treatment.

And I think that that's an area that we need to study. There is a little bit of data in other cancers, but not in myeloma. What about in patients who already had cancer and in survivorship states. So after. And you can think about it as could lifestyle changes prolong the time in remission? And these are hard studies to do because you have to control for so many different things. But we have some glimmer of like understanding where it may potentially help, right? So we're seeing here that microbiome diversity is associated with survival, suggesting that a healthy microbiome is associated with better survival. We published Dr Dr. Lesokhin and Dr. McLachlan and myself looking at myeloma patients on lenalidomide maintenance. And what we saw is patients who have better microbiome diversity, better stool butyrate producers and butyrate concentration, actually are more likely to be in sustained MRD negativity or in like two time points one year apart. Have MRD negativity as you heard about that before, suggesting that the microbiome may influence it, but that's what we need to study better. We also looked at their diets and we see an association. Again, this is a small study, but we're seeing associations where dietary flavonoids, which are plant chemicals, healthier proteins are associated with response. So we're trying to study how patterns of diet affect the microbiome and mechanisms which may affect myeloma control. We have this study also open and enrolling. This is almost finished enrolling, but we still have a little bit left.

But these are new patients who go on maintenance. So this is a quality of life study looking at two different maintenance. For this study, people need to be coming into MSK at least once a month. And this is after their induction therapy when they're going on maintenance and only 15 patients in each group are given the diet. So we're going to have that data hopefully in the next few years. So now moving on to just some practical tips or how do we think about it? These are just some practical tips. I've not had the time to go over why each one, like why whole grains are important and associated with reduced cancer risk. But just summarizing the the important things that you could think about when you are. Prioritizing whole grains. Carbs are not bad, carbs are good. Whole refined grains are what we want. Whole unrefined grains. We don't want the refined, processed, sugary carbohydrates as much as we can limit that. I understand we all enjoy that sometimes. And I'm not saying never, but I think just reducing it much less, if we can. Fiber, at least 30 grams a day. Prioritizing plant protein sources, beans, tofu, tempe. If you can, reducing red and processed meats. Fermented foods very good for you if you like them. And then thinking about unsaturated fats, where you get them? Nuts and seeds, if you can add a little bit every day to your diet and thinking about how diet, frozen fruits and vegetables are also equally healthy if not more than fresh. So if you say like, oh, I don't have access to produce, I don't have time to go to a grocery store every day.

You can buy beans in a can. You can buy frozen fruits and vegetables and have that in your freezer. And even that one serving of it is equivalent if not better, because when they pick the fruit and freeze it, it's right when all the vitamins and nutrients are ripe in it. So it's actually very healthy even you're eating it from a bag. So eating healthy doesn't have to be boring, it just needs some planning and showing you pictures. Because many times when people think about fiber rich foods, plant rich foods, they think salads and they think that that's what they have to eat alone. But we're not talking only about salads. It can be cooked foods too. And there's a lot of things you can do. Just the same things you like. Just if you like a burger, maybe think about a veggie patty instead of a hamburger. Small changes like that. You can think about those. Those may go a long way. So many times when, again, when I talk about this, people think, oh, plant-based diet means you are saying vegan. Remember, vegan is not a diet, it is a lifestyle and it is based from ethical and environmental reasons why somebody is doing this. And it doesn't have to be healthy because you may eat Oreos and french fries all the time and that's vegan still. Vegetarian often is from religious perspective.

And remember, dairy is not, doesn't have fiber and dairy is not plant-based. So even if somebody is vegetarian, but most of their diet is coming from dairy, they're not really plant-based. So same thing with eggs, right? So what what we're talking about and then high fiber plant-based is where you're getting a lot of fiber rich foods and whether you are vegan, vegetarian, pescatarian, mediterranean, paleo, low carb, keto, whatever you call it. But you are getting most of your calories from fiber. And this is the food plate from the Canadian guide, actually the food plate. And you can see half the plate is vegetables and fruit. A quarter is whole grains, a quarter is protein, but it is mostly plant protein. And this is actually from Canada's national guidelines. So it's not something making up. Few things we'll just talk about. I think we have a few more minutes left. So just maybe some trivia to wake everyone up if they were not listening. How much do Americans eat on average? And when you think about added sugar, could someone tell me how many teaspoons you think of sugar people are eating. In a day? So 10 to 30 is the range. I think y'all are pretty close. It's 17. So think about 17 teaspoons,. What's what 50% of the population eats. You all wanna be above average, right? So you wanna get that number way below 17 and a six to nine is what the guidelines say. One can of coke is gonna give you 10 teaspoons already. Cereal often will have added sugar. You don't know. So four grams is one teaspoon. When we think about fiber, how much do Americans eat on average? We kind of talked about this and we said it's not a lot, but it's half of what we need. So 10 to 15 grams is what most get. What you really want is double that. And that's, so if you, if you are at the average of fiber and you just add one cup of beans every day to your diet, you're gonna meet the fiber requirements.

So that's a quick way, because fiber, beans, one cup of beans is 15 grams of fiber. When we think about salt, on average, Americans eat 3,400. You want it to be less than 2,300. But remember most people, it's not the added salt on the table that's the main driver. It's the processed foods and things where you don't even realize there's salt in it and it's coming in that. Fruits. 0.9 cups. I like I showed you only 10% actually meet those guidelines. We wanna actually double that. So if you eat one banana, you're getting close to your daily intake. Same thing for vegetables. It's about half what you really want. And then what about protein? Do you think Americans are getting enough protein? No? No, would go with the theme, right? They're not getting enough of anything. But actually we're getting too much of protein. We get double what is the requirement. I'm not saying that every person we have to match the exact RDA, but 80 to hundred grams is what Americans eat on average. And what is the actual recommended is about 48 to 72 and 72 is on the higher end too. If you think about .8 grams per kilo is the RDA, but if we say let's, we need it higher for older people, patients with cancer, things like that, maybe it's one to 1.2 grams per day. That would be 72 grams for a 60 kilo person.

So we really want to think about it that way. And still we just focus on protein. I see it all the time. It's like, oh, I'm not getting enough protein. But think about the other things, it's more likely you're not getting enough fiber. So recently I came back from Peru and Yellack told me I should put in this picture and talk about it. So I added this yesterday. But what does facing cancer have in common with climbing a mountain? My experience with going through Hodgkin's eight years ago, lymphoma, and then going to Peru with eight other women myeloma doctors recently. And so I think like, I've seen both sides and I'm I'm asking you, do you think there's anything in common with that? Prob, in some ways no. But in some ways, yes. We are both put, we are putting our bodies through hard challenges and we want to be our fittest as we face them. So, and going through both of them, I will say going through cancer is much harder than climbing a mountain. So if you are able to go through that successfully, then you are able to do a lot of things than you have more potential than you believe you do. So it's important to think about how do we optimize our health beyond just thinking about, okay, I need to get the treatments. But there's lots beyond and around that you want to do, exercising, eating better.

And sometimes it's hard. It's hard because we live in a society that it's not easy. You have to think about it, you have to plan. But if you make it part of your habit, then it becomes easy. So the initial part takes time. So these were the eight women doctors. We just came back in July and we climbed to 17,000 feet. So when I did this, actually because of my chemotherapy, had gotten Bleomycin, which is a drug that affects the lungs. So my last dose of that chemotherapy was held because I had some lung toxicity. And so before I went, I actually got pulmonary function test to make sure that my lungs were fine because I knew this would be a problem there. Luckily it was. But again, those are things we do all the time, right? Like we optimize our health with those things. But that's not enough. Like we have to do the other side too, which is what we're talking about here.

So my Peru hike was a hundred percent fiber fueled and it was still successful. So I, and lovely colors of food and great things to eat. So think about some goals you wanna pick, at least pick one to begin with, whether, it doesn't have to be everything together, but just think about one thing that you will do and then slowly you can add them to it. So I think when we think about future directions, we wanna do more of these interventional studies. And I think obviously getting funding to do these kind of studies takes time, but hopefully we will. So let's change our focus from living longer to living better and longer and incorporating lifestyle into our life. So that I'd literally like to thank the IMF. Thank you all for listening and patients who've taken part as well. Thank you. And I do post a little bit on social medias. It's urvishahmd but, you can get a lot of the information on talks that I've given also through IMF on their webinars as well. And we're gonna be doing a Facebook live, I think later this month.

- Wow. Every time I hear Urvi, I don't know if I should cry because I'm not eating right. I should clap because she's taught me so much. She inspires and she educates at the same time. So thank you, Dr. Shah, for that extraordinary presentation. And it just really, your own resilience, what you went through. I don't wanna get choked up, but what you and those incredible myeloma women did in Peru is fantastic. So we are towards the end of our day, we're almost done. I'm gonna ask our panelists to come up. So, Dr. Fonseca, Dr. Vescio, Dr. Lonial, Dr. Dispenzieri, Dr. Shah, Teresa Miceli. If everyone wants to come up and have a seat here, we will launch into our Q&A. So we'll be ready to get your questions in a few minutes. Oh, you're all too nice. Just walk up. Before we dive right into questions, because we didn't have the chance to hear from Dr. Fonseca and Dr. Vescio yet directly. You can actually probably do it from one of the seats. I'm gonna ask each of them to just chime in a few comments about their thoughts around the day thus far. So start with you, Rafael. I know that we're gonna do a Facebook Live on the discussion around the future of myeloma, but maybe having joined us today, you can share a little bit with us about your thoughts. And I'll just quickly also mention that Tiffany unfortunately had to leave 'cause she's going to LAX, everybody's favorite place on the planet. Godspeed, Tiffany. And so Teresa kindly will join us from a nursing perspective as well. But, Rafael, any thoughts from the OG as I described you this morning, the original gangster on myeloma.

- Thank you for that, Joe. That's really nice. Well, it's such a wonderful day and we, as you know, physicians engage in the care of myeloma patients, researchers, and ultimately members of the community. We always learn so much from attending this event, and I'm sure you do as well. So this is a, just a tremendous opportunity to come together. One of some of the comments I was gonna make, were related to the future of myeloma, the future treatment for myeloma. Like all of you, we want things to continue to improve and be better. Whenever I meet a patient for the first time, I tell them that, I know you've read about this online and probably the first sentence in all book chapters and articles is that myeloma's incurable disease. And I state that I disagree with that. I think we already see that for a minority of our patients, and we want that to be true for the majority of our patients, however we define that. And I think we're getting there because of the tools that we have, the advent of better treatments. I have a slide I use that when I talk, which is one of my first slides that I showcase. The survival we had when I was in training where at the time with naltrexone and prednisone, we were seeing a median time for about two years. And obviously things have improved dramatically with much, much longer survival for our patients. So it's just been humbling to be part of this process and to see the improvements that come from better treatments and better understanding of the disease. So I tell patients, I can't promise you that's gonna happen, but we're gonna try as if we're gonna get there and we'll do the most to maximize the duration of the disease control. So again, as the future of research becomes your present in that future, we have those options. So that's a very, very important aspect of how I see things. And I was thinking of very quickly just to finalize a comment of gratitude to all of you. You probably have heard us say thank you for your trust, thank you for your participation in the clinical trials that have advanced care so much. And indeed we do that whenever we present clinical trials. But there's another aspect of gratitude that I'd like to share with you today, and that is that quite frequently, I'm in a dinner and I tell patients I'm an oncologist, and the first reaction is, "That must be horrible." Oh, and they look at you like, "Poor you. That's really a bad professional choice." And little they know what an honor and privilege it is to participate in situations where we clearly understand that you as a patient would not want to be there. But just to be part of the current time where we can help patients live much longer, much fuller lives, and as we saw from Dr. Shah. By the way, your talk is quite inspirational. Makes us think about I doing everything we can. So that gratitude, I'm just gonna finish by saying the gratitude is for the meaning you give to our lives as oncologists, as we participate in your care. My full clinic day is usually on Tuesdays, and I always tell people when I walk in the parking lot, I get off my car, I go towards my clinic, there's an extra pep in my day just because it's my full clinic day. So for that, we're grateful as well too. So thank you, Joe.

- Wonderful. Stated so well, I love how Rafael likes to make that comment so clearly that everywhere you read myeloma is incurable. And if he disagrees with that, then we have to listen because well, he's the og. But I appreciate your optimism, your gratefulness, Dr. Vescio in many respects you are of course the OG of LA in the sense that I've had at least half a dozen patients come up to me today and say, "Well, I'm with Dr. Vescio," and I always say, "Thank God, I know you're in good hands with with Bob." And just want to give you a few minutes to make some comments about what you've experienced here over the last couple days and your thoughts about the way myeloma's moving.

- Oh.

- It should be on. As Rafael.

- He got it.

- Yeah, it's working now.

- I mentioned, I mean, it is-

- [Technician] I have to rebalance for each of your mics 'cause you're all a little different. So when you first just talking, just keep talking, I'll rebalance it as you all are going. No need to switch mics or anything.

- Just speak right into it, so it's loud.

- Okay. So as Rafael mentioned, I think it really is a privilege to be helping patients are doing, trying to do our best to help you all not only extend your life, but improve the quality of your life. And I think that's kind of a theme of today. Every patient here had kind of a, has a different story and and I know I learned so much from each person's experiences and what they go through and just kind of adapting and trying to match your treatment with your goals. And we have so many medicines now as Sagar mentioned, I thought that's a brilliant idea is to kind of attack it kind of repetitively with different, using different targets and hopefully we can get patients off therapy and of with a long lived quality of life. So I think the future is really bright for Mopa myeloma. I know sometimes people are, as you heard, understandably quite fearful of the disease, but there's many in the room that you heard from today who've been living with this for many, many years. And sometimes I fear the worry for some is it can be worse than the disease. So it's a balance of trying to adapt and have your disease controlled without having the disease consume your thoughts and interfere with the quality of life you deserve. So I really, again, I feel honored to that people trust me and be part of this task to try to get this disease under control. And as we heard, we're all kind of friends in this group. I think that's what makes the myeloma field seemingly much better than some of the other groups like lung cancer and leukemia where everybody seems to have a different opinion and one state why their opinions better than the others. So, it's a great meeting. Thanks for inviting me.

- [Joe] Yeah, there would be no one here on this panel who would say that they're always right, Sagar. I mean, sorry.

- Yeah, I disagree

- [Joe] Okay, thank you so much, Bob. We appreciate you. You have been just a tremendous source of blessing to so many patients in this region. The number of times in a week I hear the word SEO is spoken in positive is really, really encouraging. So, thank you. So I think we'll open it up now, 'cause I know that you've probably been building up questions over the last day and a half. We still have quite a bit of time for Q&A. So please raise your hand and we've got lots of mic runners, I'll be more than happy to bring questions. And we have all of our panelists here, so whether it's-

- [Speaker] Can you give this one too?

- [Joe] How do you get more fiber in your diet to how do I measure an M-spike, fire away. I think we've got question at number three.

- [Audience Member] I have a question about bile acid malabsorption. I've been on Revlimid for five and a half years and had a pretty severe case of that and took a bile acid sequestering. I finally said I need to get off of this for my quality of life. So my question is, it's been over a month. Are there tools or ways to get off the sequestering and to get back to a normal, have a quote normal GI tract. I mean I always felt like, "Gee, I'm taking a drug to take a drug." So any tools or suggestions or what are the long term effects of bile acid malabsorption?

- [Joe] So maybe, Urvi, do you wanna start with that?

- [Urvi] Sure.

- [Joe] Then Teresa, if you have more comments?

- [Urvi] Did you say you stopped lenalidomide?

- [Audience Member] Yes, well, I recently stopped because I thought I needed a break and I was an, I'm going on a trip and I just didn't wanna be in the bathroom on my trip.

- I get that. So I think, so bile acid, one thing is that there is some data suggesting that maybe fatty foods could make it worse. So for some people that helps. So trying to see if avoiding that. We are studying this in our trials. So the maintenance study I showed you, we are looking at diet with lenalidomide maintenance and we had one patient who said that their diarrhea improved. But that's just one anecdote. So of course we need to understand and we're also looking at the microbiome in patients who have diarrhea and not, so hopefully we'll have more. But I think avoiding fatty foods. Another thing is lactose intolerance is like actually very common. It's 70% of the population. And I think when we do get things like chemotherapy, we might actually, where somebody may have mild lactose intolerance, it might be getting worse with it. So thinking about trial of different aspects of, and see if those things help with it. But otherwise, for now the bile acid sequestrant seems to work the best. And I don't know if anybody has other thought.

- [Joe] Bob, do you wanna comment?

- Yeah, I think it's a common kind of scenario for people that are on lenalidomide, Revlimid for a long period of time and they do well and then quit doing well. And then it seems to build up, I had a lady this this week said she was fine but she told me she had 10 to 15 episodes of diarrhea every day, but she was managing, so that just seemed like not a quality of life that seemed reasonable. So, the bile acid sequestrants can help. There's other drugs. Sometimes it's just like for bortezomib, it can cause neuropathy even if it works well, there's other agents that might work well in its place. It can take a long time to recover. So it can some people recover in months, but some take, even I had a lady I saw last week, it's been a couple years and she's better, but she's still not quite back to normal. So I think that's the balance of trying to, you want fix the disease, but then if the disease is causing so many problems with the bile acid malabsorption, you have to consider a different drug.

- [Joe] Yeah, I think... Oh sorry, go ahead, Teresa.

- Sorry. Well, the only thing that I was gonna add to what was already said is the assumption is that it's the Revlimid and maybe that is absolutely true, but is there a need for further evaluation to rule out other issues? It's been a number of years this has come on. Could it be something now related to being, having a compromised immune system being on Revlimid for long term or any other things, diet-based allergies, colitis, things of that nature.

- And now we're gonna try to answer your questions really quickly, but I'm just gonna add one more comment to this. Is it also, as we've discussed a lot this weekend, I mean it also really comes down to deciding is it worth staying on the Revlimid, right? So sometimes people hear talks and they say, okay, Revlimid maintenance keeps people in remission for longer, maybe even prolongs people's lives. And people take that as a directive. Like again, I said yesterday you'll take it and you'll like it, that I am not gonna stop this Revlimid, I only have 15 bowel movements a day, Dr. Vescio, it's all good. And I look to the spouse and the spouse is like, "They never leave the house anymore. They don't do, they don't play pickleball anymore," or whatever else that they used to do. We have to balance that with the relative benefit. And I'm not gonna say that Revlimid doesn't have benefit in maintenance, but I would also look at how long you've been on it and the relative benefit versus coming off. And there are times when people just need to come off the drug. So we can't always mitigate the side effects. So that's again, back to the conversation we had yesterday about the importance of building a relationship with your healthcare team where things can be discussed openly and honestly, because especially when someone's been on Revlimid for a couple of years, we start to wonder how much more benefit they're getting from it. And when it's compromising someone's life, it's very reasonable to stop it.

- I will say, Joe, that the biggest issue we see is that people are not taking enough of the colestipol. So they take one tablet once a day and think that that's the dose because most of the community guys don't know how to use it. If you take enough, which is usually three tablets twice a day, 95% of patients have their diarrhea go away. And the most common side effect is that it drops your cholesterol. So, okay, I don't know anybody that's gonna be too upset about that. But again, it is a balance of time and what is the relative cost of taking an extra medicine to take a medicine as you suggested, versus the potential upside of long-term therapy.

- [Joe] Great. No thanks, Sagar. Question number one at the back.

- [Audience Member] I'm so grateful for this panel and the expertise. So my question is, so how are people diagnosed asymptomatically, like with MGUS or smoldering, how does that happen? And so the reason why I'm asking this is because I'm grateful for like the drugs that are coming out that are extending lives and saving lives. But a lot of us are broken, a lot of us have kidney disease, have just bone, they have got ton of lesions. And so how do we make it so that people are being diagnosed asymptomatically getting treated earlier so that they're not physically broken so that their quality of life ultimately is increased throughout their treatment journey.

- So maybe I'll start and see point someone else wants to add to it. So first of all, for the record, I did not plant that question. But I may have. Thank you, brother. Great question. I mean I think it goes back to what we discussed a little bit and what Sagar and I discussed on the future of myeloma concept this morning, which is that, you know, the goal is always to intercept or to catch cancer early on and that's what led to the screening of breast cancer, screening of colon cancer. We're not quite there yet for myeloma, but we feel, I think most of us probably agree strongly in the next several years we'll have guidelines around trying to catch it early, 'cause we have a lot of evidence now that intervening early makes a difference even in the difference when Teresa and I showed yesterday the difference between CRAB and SliM CRAB, when we added those three new criteria to myeloma, believe it or not, 10 years ago in 2014, we had some clinical trials at the time where patients were enrolled either with CRAB or with SliM CRAB and we could follow their outcomes. And it was clear that those who had SliM CRAB, meaning they did not yet develop CRAB features, did better in the long run. So a lot of that is education around when to think about myeloma. The challenge is we tend to think about myeloma when people have those symptoms already. So when it's diagnosed asymptomatically, what I call the incidentaloma is typically because someone got blood work because they're getting an insurance test or their doctor was thinking about something else or somehow or their total protein was elevated for another test and it led down that way. And that's good in the sense that it's nice to detect it early but it hasn't been a strategic approach. I dunno if there's any other comments to add to that.

- I would only say that for those of you that were diagnosed incidentally by somebody being very astute and aware of an elevated protein or just a slight change, send chocolates to that primary care doctor on an annual basis.

- Absolutely. And that's why I mentioned even with Empower, we're working so hard with the primary care community to educate them. Is the next question with you, Danielle? Perfect.

- [Richard] Yes, thank you, panel. It's been very informative the last two days. One of the pressures we have in myeloma patients is financial. It's always a worry are these great novel drugs gonna be covered and how are they gonna be covered? And that's almost as much of a burden as the disease itself. One of the things we heard yesterday from one of your panelists who's I don't think is there today that for us on Medicare there is going to be a cap on the what I consider the pills that we take to $2,000 cap of out of pocket. But I'm curious why some of the wonder drugs we take, and I'm taking one of them are have to be IV and are not pills. If they were pills they'd be covered. And I'm wondering why that is. I've heard various stories. Perhaps obviously you know why that is, but we could really help the financial drain if we could get, for example, Dara on pill form rather than IV, it would be covered with this cap. So, what's going on?

- Yeah, so the irony of that question is that until that change it was always the reverse, right? So historically cancer therapy was always viewed as being intravenous and that's why IV coverage was always so much better than pills and the burden of finances was on the insurance company. But when we developed all these pills, the financial burden was on the patient and the goal was to create as many of these new cancer therapies as pills because although you love your doctors and we love going to visit Dr. Vescio, I'd rather take a pill at home than have to go in to see the doctor. Now with this new change that Danielle described yesterday, the paradox is we flipped that. I don't know if anyone wants to comment on how hard it is to make drugs like Daratumumab orally. Maybe Rafael you can comment on that.

- Yes, no, it's a great question. Everyone would like to get drugs that are very simple to administer and safer for patients. But sometimes you can't. For instance, Daratumumab probably will never be pill. The reason, the main reason is something we call a large molecule. So if you were to take that as a pill, our body would digest that. It would be the same as eating protein in a steak. Just cannot pass through the gut. And some drugs, there has not been an oral Velcade-like or kyprolis-like medication. There was an attempt to do that but it turns out that was too toxic. So it really depends on the medication. I think we doctors would love to see everything being pills and very, very simple. But a lot of that depends on the chemical structure of those medications.

- Excellent. Next question. At the back here. Yep, number one.

- [Lisa] Hi, thank you. I agree with Richard here. I'm very grateful for everybody who's here speaking and giving us your expertise.

- Thanks, Lisa.

- [Lisa] But I had a question about plasmacytomas and then also about the translocation 11;14. So regarding plasmacytomas for patients who are diagnosed with active myeloma because of a plasmacytoma, is there any prognostic value in that? And then my second question is about t11;14. I've met a lot of people with t11;14, I'm one of them. And I've heard that it is now intermediate risk rather than standard or high risk. What does that mean? What is intermediate risk? And the last thing I'll say is Dr. Fonseca when you said that you're grateful, you have gratitude for patients for giving meaning to your life, that's just amazing. And so for anybody out there who doesn't have a specialist, that's why we see our specialists 'cause they're amazing people.

- Well, thank you, Lisa. That's very, very kind. So maybe what, why don't I ask, Sagar, do you wanna comment on the plasmacytomas, and then, Rafael, do you want to comment on the 11;14?

- So plasmacytomas come in two flavors. If it's a plasmacytoma that extends from a bone, then we consider that sort of a medullary plasmacytoma, which is really just a growth of the myeloma outside the bone marrow through the bone into an, it's not considered to be prognostically any worse than what I'm gonna describe next, which is an extramedullary plasmacytoma, which is a plasmacytoma in the skin or in another area where it's soft tissue associated but is not directly connected to bone. That tends to be associated with high risk disease. Those are cells that have figured out how to grow outside the bone marrow microenvironment. And in that context it is a lot more challenging for us to treat. We can shrink them temporarily, but they're hard to make go away in the long term.

- [Joe] Rafael, 11;14.

- And, Lisa, thank you for the comment and the question, t11;14. It varies a little bit because at the beginning we used to think it was a better prognosis because of the treatments that were being given back then, which was mainly Melpha. Then it turns out all myelomas appeared to do better and that was because of the advent of the Revlimid and the Velcade. But it turns out, when you look at the groups, the 11;14 didn't get as much benefits from those drugs. I think partly has to do with the, you know, what we would call the biology. So you know how the cells are, they're slightly different, they tend to be smaller. We describe plasma cells, if you look at them in the microscope, they look like a fried egg. And the 11;14 is like a fried egg that's missing a lot of that white, it has scanned cytoplasm. And we think that is really important for the Velcade and the Revlimids to work. But now that you bring drugs like the Venetoclax and the Venetoclax like, I think there's gonna flip again towards that being a favorable finding. So I think as at the end of the day how we classify it's not as important as to making sure we have the right treatment for each one of the subtypes. And the 11;14 is quite interesting, but there's some patients that are very indolent and there's really good 11;14 biology if you may. And then the 11;14, if it doesn't present in the right way, can be very aggressive. And I would presume for most of you who are here who are 11;14, that has not been the case. Sometimes we see this primary plasma cell leukemia, very aggressive myeloma from the get-go in some patients who have 11;14. But for many patients, you know, it still has that more favorable outcome.

- So, one quick point about 11;14, if you look at, and some of you are in my session saw the RVD 1,000 data that I showed. If you're 11;14, your first remission often is shorter than the standard risk patient to sort of speak to Rafael's back and forth. But because of the availability of drugs like Venetoclax, the second remission actually makes up for that if you get Venetoclax. So the survival ends up being as good as a standard risk patient, but that first remission can be shorter and it's really about access to Ven that makes up that delta.

- Excellent. It speaks to the complexity when you spoke even at your session, Sagar, about how high risk disease is defined 80 different ways and becomes complicated. And again, if I could just comment, mention this very quickly because I think sometimes people see, we saw a beautiful question asked by someone earlier who's high risk myeloma for 12 years. That these, each of these different factors that predict high risk versus standard risk, none of them are perfect. We've all had, I sometimes use the analogy saying, if there's a 40-year-old man driving a red Corvette out here on the highway, are they speeding? Well, first of all they're not 'cause there's so much traffic. No, but assuming that there wasn't traffic. it's a predictive thing that that person, you're gonna assume that that gentleman is driving the red car fast, but he may be in the slow lane being passed by an 80-year-old woman in a white Cadillac, right? So, these things are not always perfectly predictive, and so that's why the individual nature of myeloma is important. We all have patients in our practice who have so-called standard risk myeloma, but then unfortunately relapse very quickly and we don't know why. And on the other side we have patients with so-called high-risk myeloma who actually do very well with treatment. So, we just have to be careful that you don't feel that branding that makes it sound like there's no hope for someone with high-risk myeloma.

- [Audience Member] My question has to do with asking questions at appointments of the oncologist because at the beginning we had a million questions, but now my dad sees the oncologist, he's on maintenance and sees him, his oncologist every six weeks. And so what are some good educated questions to ask to get the most information about where he is and what's happening?

- I'm gonna start with Teresa because if only we had a tool that was created by the IMF that listed questions for patients to ask their doctors. Oh, if that were only true.

- I think we should maybe have one out front. We actually have a couple.

- That's right, we actually brought some of them with us.

- Yeah, we do have a couple of tools, decision making tools, things of that nature. But I think your question is really, and it might be a little bit more individualized, but in general, where is a person at right now with their diagnosis? Are we at a point where you've gone through first line of therapy. And I think we can do better at defining what line of therapy is in the way of you've had the Dara-VRD or VRD induction, stem cell transplant, you're on maintenance, it's been a few years. You hear all these things about, it's at some point the myeloma's no longer gonna respond to the Revlimid. At that point, one of the questions should be, so right now things are going good, but what would be our next choice? What would be our next option for therapy? Kind of planning ahead. Maybe you're on your third line of therapy and you've heard something about this CAR T thing. For me as an individual, one would be a good time to be thinking about CAR T. Should I have a referral to meet with a transplant or a CAR T specialist, so that I can at least be in their realm. Like at Mayo Clinic, if you haven't been seen by a Mayo doctor in two years, you are no longer an established patient. You become a new patient. And that can sometimes have its own challenges for kind of getting back in the door and seeing the same person that you were seeing previously. So it kind of depends on where you're at in the process and wanting to make sure that you're thinking not only about the here and now, but what are our next steps. We've always gotta be thinking a couple of steps ahead.

- And then, Dr. Dispenzieri, if I can ask you to comment here as well, you know, from the doctor's side, sometimes we have patients come in with a sheet of paper that has 64 questions on it. I had a patient a few weeks ago, literally 64 questions, right? And I remember I trained under a doctor who used to say to their patients, "Every time you come to the office you're allowed to ask three questions." And the person came in and said, "Am I only allowed to ask three questions?" He said, "Yes, and that was number one." So, he was a little bit too harsh. But can you give us from the clinician, 'cause we know you see a lot of patients, what tips or what things do you want your patients to know? Do you want them to write them down in advance? Are there a couple things that just come to mind that you say, "I wish patients did this when they came to their appointment."

- Yeah, I think writing things down is great. I think knowing why you're asking the question. Like it's one thing if you have a list of questions you heard you should ask these things. Sometimes people are so anxious they have this list of questions and they're not listening to the answers. They're so, they wanna do it right. I wanna be a good patient, I wanna be an informed patient and I gotta get through my questions and they're just asking the questions and they don't wanna listen. And I get it 'cause that's anxiety. And it's hard being a patient. But I think that it's perfectly good to be writing down your questions 'cause you forget, you freeze like a deer in the headlights when you go see the doctor sometimes. 64 probably isn't a good number for one visit, but sort of prioritizing them or sometimes sending a note through the portal or something or through the message system, so that the doctor can answer questions. Sometimes it's best to answer questions in paragraph form rather than question, answer, question, answer, question, answer. And if your doctor's a good communicator, sometimes I have patients that come in with a long list and I just start explaining things but I say, "We'll do your questions after. I promise." And then they go through their list after I'm done talking and they're like, "I think you got them all." And it's like, "Okay, good." Or if I didn't get 'em all, then I answer that one.

- Well, that's great. I think the other piece of advice I'll take from Robin and Michael Tuyi who often say this is that when possible bring someone with you 'cause you've just multiplied the ears, you've gone from two to four ears and now there are nuances and things that one might pick up and the other might miss and vice versa. So, it bolsters the ability to hear more.

- And I'd just like to add, it's not always about just asking questions. It's also about sharing updates from your own experience. And one of the things that I've heard all too often is, well, I've already mentioned that I've gotten neuropathy, so I just stopped mentioning it. It's a constant in your life. And if it's not being addressed, it's not because people don't care or they can't do anything, but it may not have stayed in my consciousness, but it stayed in your feet. And so making sure that if it's a constant issue that's affecting your quality of life, don't hesitate to repeat yourself until you're heard.

- Excellent. I know our time is almost gone, but I think we'll take two more questions.

- Joe.

- Oh sorry.

- Can I get just a quick comment?

- Yeah, please.

- So one time, sometimes what I'll notice, and this happened to me probably a few months ago, where a patient's family brought in 15 papers and they brought them one in one and said, "Do you know this. Do you know this? Do you know this?" And when they got to the 15th they said, "Do you know this?" And I said, "Yeah, that one's mine." So, I think the idea about knowing what you're asking is really important. When you see a specialist, we, this is all we do, so there's a certain level of knowledge that you have to anticipate that we have when we come into it. But the second part is we've been to school a long time to do this and we've been doing this for a long time, so pattern recognition is just sort of natural for all of us, particularly when it comes to myeloma. And you have to have a certain level of trust. And if you don't have that level of trust, if you're questioning everything that the doctor or the team are doing, then maybe that's not the right place for you to be because 64 questions is a lot of questions. And at a certain point you do have to believe that the team that's looking after you knows what they're doing. And if you don't feel that, then all the questions in the world aren't gonna solve that. You probably need to be in a different place.

- And I'm not trying to shamelessly be a commercial for the IMF, but let me be a commercial for the IMF. When patients often come to see me, our medical assistant or our nurse practitioner will say, "Yeah, Dr. Joe, we have another electronic stalker. They've watched all of your videos." We do have obviously a lot of resources as Robin walked through yesterday on the website. So very often you can be prepared more before especially going in to see a new specialist or getting an expert opinion or on a particular topic, whether it's CAR T or all these new bispecifics that we have and another one coming soon that you can gain a bit of that, at least general information and then individualize it at your visit. All right, we'll take two more questions. I know we're running a little bit late, but this is so great to see so many great questions, so why don't we take two more. Start with you at the back, Danielle.

- [Danielle] A friend of mine who is in our support group recently had CAR T and developed a brain tumor about two months following and they biopsied it and it was myeloma and origin. Do you feel that this might be a risk that we might see as more CAR Ts are going to be probably down the line for many of us patients?

- I'm happy to answer that, but I'll see if someone else wants to particularly address that. Rafael?

- Maybe just very quickly. No, unfortunately if they found myeloma in the brain, that means that those cells were overcoming any effects of the CAR T, so it wouldn't be related to the CAR T itself. And it just unfortunately means that the CAR Ts are not able to control that. It's particularly harder in the brain because our body tries to protect our brain with a number of things, including something we call in medicine, the blood-brain barrier, which exists naturally to protect from harmful things to get into our brain, but also that makes treatments also harder as they try to get into the brain.

- And I think if I just add to that, I completely agree that that's not, the CAR didn't cause that, but there is some press and there was the FDA announcement last November about the potential for CAR T cells to induce T-cell cancers. And again, like we've said with everything, every treatment comes with some risk, right? Unless it's a mother's milk, everything comes with risk. That's why you go and you get aspirin from the pharmacy and the list of potential side effects is pages long. We don't want to minimize those side effects, but we also have to put them in context that there are still things we're learning about CAR T. It turns out, for example, this T-cell cancer is coming from CAR T happens somewhere around one in 2,000 patients. And that's relative to the fact that the majority of those 2,000 patients are gonna live longer because of their CAR T. So there's kind of the devil you know, the devil you don't know. We've been down this road before in myeloma knowing that certain, some of our maintenance therapies and transplant itself can slightly increase the risk of a second cancer, but it's also controlling the cancer that's there. So, I think we always have to put these things in balance as we look through them. And that's why it's so important to have that conversation with your doctor. We hope that some of the side effects we're seeing from CAR T, some of the neurological side effects, some of the other challenges will be reduced with time, both as we understand it and treat it better, but also as we develop new CAR T products. And we'll take the last question here from Malcolm.

- [Malcolm] Yeah, hello?

- Yep, we can.

- [Malcolm] The question is, what is the role of cannabis in all of this? Cannabis can help with pain, fatigue, anxiety, sleep. No one has mentioned cannabis.

- So I'm not gonna ask one of the Mayo people to talk about this because when I was at Mayo I remember that it was like, that's the word that we don't use. But I don't know, Bob, I mean you're in ganja town, I mean LA.

- It's is California

- Would you like to speak about that?

- I had a feeling it was coming my way. I mean I think that for some patients that cannabis helps them adapt and tolerate the symptoms and side effects that the cancer caused and also the treatment caused. So certainly people with CBD putting on their neuro, their feet where they had neuropathy, that clearly helps. I think it's beneficial for certain people as a way of addressing their pain and sleep and things like that. When it first came out, everybody was excited and they were thinking it's curing cancer. And I'm not gonna say I'm a believer in that. I haven't really noticed patients taking it doing better than those who don't. But I think it can help for certain people, their symptoms. And that's important too. That's really important.

- Yeah, and I don't think it was sort of purposeful that wasn't mentioned. Maybe I'll wear my Canadian hat for a minute because we've been using cannabis in Canada. Well, Canadians have been using cannabis in ways that we won't describe today. But no, I really do think there is a benefit, but it is likely a limited benefit and it's mostly on a symptomatic side. I agree with Bob that way. I think there was some excitement that some of the variants of the product are gonna be anti-cancer are gonna cure all. We're just not seeing that. But there is no doubt I've had so many patients in particular from pain, nausea, and anorexia that have really benefited in addition to what Bob said with the oils for neuropathy. And so it is something that is very legitimate. Depending on the healthcare system that you're involved with, some are more qualified or less qualified to do it. Very often our friends in palliative care have a lot more expertise in the area. And we should not think of palliative care as just being hospice care when we're not giving direct to active therapy. Palliative care is something that supports patients all along their journey. Even at the earliest intervention. We've shown that palliative care actually improves quantity and quality of life of our patients. And so if that's something that you wanna pursue, then I would try and go down that angle. Sorry.

- Well, the only thing that I'd add to it is I'm not a big fan of putting anything into your lungs other than air, and so the smoking route is something that I'm not a fan of, and the increased risk of fungal infections.

- Right, I don't think you'll find a single recommendation of any oncology group on the planet that the inhalation version of cannabis is of any value. A little bit different obviously when it's in medicated form or brownies. But we just heard a talk about a dietary phenomenon, so I won't go into that.

- It's plant-based.

- Plant-based

- Let's take a minute to thank everyone on our panel. And I will just comment that I'll bring the boss up to close us off. Come on up, Yelak, to close us off. But I will just remind everyone to please fill out that evaluation. You have it there. Take the time to do that. It's so helpful. As we mentioned from the start, we really changed the way we're approaching the Patient & Family Seminars with a very different method and we hope it's been of benefit to you, but please let us know what we're doing well, what we can do better. And I'll let the boss come and close us off. Thank you so much.

- Thank you, everyone. One of the things Dr. Lonial said was that there needs to be some level of trust between the patient and the clinician. And then if that trust doesn't exist, probably you need to find another clinician. And the reason is this for me. If there is data to support what you are doing, if you are a newly diagnosed patient and you need to be on three drugs or four drugs therapy, there is data to support that and anybody can treat you. When there is no data because you have relapsed it or you have comorbidities that are not necessarily studied with that data, then there is guidelines that the IMWG, the NCCN and others actually develop. So that's also kind of okay to have a doctor that may not necessarily be a myeloma expert, but at some point you run out of data, at some point you run out of guidelines and then you depend on the judgment of your clinician and your myeloma expert. That is why in my opinion, one, you need one of these people. If you don't have them as, or their colleagues, I don't want everybody to go and move from Los Angeles to Emory, but you need someone like them.

- [Panelist] Another airport.

- I like them. So the other two reminders is on September fourteenths there is a 12 annual Miracles for Myeloma Walk and Run in Clarks, New Jersey. And here in our own backyard on September 21st, there is a six annual Inland Empire In Person/Virtual Walk for Myeloma Miracles. Yeah. If you remember yesterday, our goal with this Patient & Family Seminar was threefold. One, is make sure that you have the knowledge or start to acquire the knowledge you need in order to be able to manage your myeloma properly. Foster communication and connection between you and your fellow myeloma patients or the clinicians that came to the stage. And then the last one was really being able to inspire hope by giving you those connections and that knowledge you need. I hope we have done that and some more as well. So as I'm very grateful for all of you because when you have a party and nobody shows up, it's not fun. So, we had a party and you guys showed up and you showed up strong. Thank you for doing that. Some of you are challenging us to say, okay, there are at least thousands of myeloma patients in the LA area. You need to do more to bring them. Yes, we can do more. And when I say we, it means you included. Tell others how much beneficial this meeting was for you. I also want to thank the clinicians for being here. We have covered a lot of ground from the latest research advancements to practical strategies for managing your myeloma. I want you to remember one thing as you go today, you are not alone. You have the International Myeloma Foundation. If you can't get access to this, any of the clinicians here or anybody else, call our info line, call the support group directors that IMF has, join a support group and help get help, the help you need in order to manage your myeloma. So as I conclude, if you work for the International Myeloma Foundation, come to the stage, please. Hurry, hurry. And you guys can. Thank you so much. You can leave the stage. Michael. All right, Peter was the first one to join us, so he will get the prize.

- [Speaker] Yeah.

- You don't have to say it. I mean, you can't just stand. I just want to, if there is something you didn't like from the last day and half, email me. I'm responsible for that. If there is something you liked about the day and half, these are the people that made it happen for you. So please give them a hand. Thank you for being. Thank you. Thank you, everyone.