The Future of Myeloma: Screening, Transplant vs Immunotherapy, CELMoDs & the Path to a Cure

Dr. Joseph Mikhael:
This is one of my favorite sessions actually of the whole year to do what we call the fireside chat. And this was born out of the fact that we used to have a keynote lecture on asking one of our experts to sort of pontificate and take out their crystal ball and predict the future. And some of you may remember a couple of years ago that we had a bit of a flight issue with one of our IMWG members who was on his way to Los Angeles and didn't quite make it to Los Angeles in time. And so we ended up pivoting at the last minute and Dr. Sagar Lonial, who many of you would know who sits on our board as the vice chair of the board of the IMF was here. And he and I ended up just sitting on this very stage and having a little chat about the future of myeloma.
And the reviews were so good about it, we decided instead of having this lecture, we'll just convert it to a fireside chat. And so in just a moment, I get to introduce you to whom will join me on the stage. But I just want to note in particular that we're so blessed today to have three of the most outstanding myeloma doctors that I know joining us today. As I like to say yesterday, I was just the appetizer. This is the main dish today. So you will have Dr. Robert Vescio, who's here from Cedars-Sinai, will be joining. I know. Yep.
You always have a little fan crowd wherever you go, brother. I'm always impressed by that. We have Dr. Sarah Lee, who's joining us from City of Hope. And thirdly, I later will introduce our leadership board member who's joining us today, for which I'm very, very excited. But thirdly, from the physician side, we have Dr. Tara Gregory who's joining us from Colorado. And Tara, I'm going to ask you to come and join me on the stage. So Tara will be pulling out her crystal ball as it were. Dr. Gregory, why don't you just tell us a little bit about yourself first because you and I are actually the two non-Californians here, but maybe you can share a little bit about yourself.
Dr. Tara Gregory:
I am originally from Scottsdale, Arizona where we first met.
Dr. Joseph Mikhael:
Yes.
Dr. Tara Gregory:
And I was a resident and you were my attending physician at the Mayo Clinic. And now I have adult-
Dr. Joseph Mikhael:
And she's still scarred by that, but people can survive that.
Dr. Tara Gregory:
And I ended up moving to Colorado for my oncology training and being from Arizona and you move someplace that's not Arizona, you say, "Oh, this is really nice." So we ended up staying and I knew that I wanted to do stem cell transplant specifically because I worked with Adrian Briggs at Good Samaritan in Phoenix. And so I ended up in Colorado, and long story short, I ended up at the practice I'm at now as their fellow. And probably some of you know Dr. Jeff Mattis and he is so involved in everything myeloma and he's really a true myeloma expert. And so under his mentorship, I ended up focusing on myeloma.
Dr. Joseph Mikhael:
Wonderful. Wonderful. It really always is amazing to me, and I know we're going to dive into myeloma, but let me just say, it is always amazing in medicine how much mentorship influences your career. I had the privilege of being the postgraduate dean at Mayo and we would survey the residents every year as to why they selected the specialty that they went into. And by far, the number one response was not lifestyle or finances or complexity. It was always the mentors that they had been with. And for you to have someone like Jeff Mattis, who's pathologically nice is really, really wonderful. For those of you who may know Dr. Mattis, he's really special. So let's think a little bit together about the future of multiple myeloma. There's sort of four areas I'd like us to think about. And then what we'll do is we'll try and cover those in about 20-ish minutes, 25 minutes max, and then we'll have lots of time for Q&A.
As I noted to you yesterday, a lot of the feedback we've received from you is more Q&A, more Q&A. So we definitely want more Q&A and we'll have more time for that today, not only during this session, but later on throughout the day after several of the talks. So the first area I want to talk about, and it's so ironic that Heather just showed us the video of the Iceland Cycling Expedition. One of the reasons why we do it in Iceland is that of course is where the iStopMM study was created. Now you may not never have heard that acronym. I'll just very quickly explain it. iStopMM stands for Iceland Screens, Treats, or Prevents Multiple Myeloma. And this was really the largest study ever in multiple myeloma, one of the largest health screening studies ever where they wanted to see if screening a healthy population is going to save lives in the long run by catching patients multiple myeloma earlier.
You may be familiar with the fact that we screen for breast cancer with mammography. We screen for colon cancer with typically colonoscopy and sometimes other tests as well. And so the question of myeloma is still not quite answered. And I had the privilege of being one of the four people sitting in Edinburgh, Scotland one evening on the back of a napkin. We drafted the concept of-
Dr. Tara Gregory:
Sounds terrible for you, being in Scotland.
Dr. Joseph Mikhael:
... doing this study. And so Iceland was selected partly because the people of Iceland were more likely going to be compliant to do so, but also Iceland have more people have had their whole genome sequenced than any country in the world. And so looking into your crystal ball into the future, they have not yet... The study has been conducted in that all of those patients were consented, the blood tests have been done. We have a lot of results from the study, but we don't have the final conclusion of does it save lives, because that will then launch us further. But if you could look into your crystal ball in the future, do you see a day where we will actually be screening healthy individuals, not just waiting for people to have symptoms or an abnormal blood test? Do you think we will be screening for multiple myeloma?
Dr. Tara Gregory:
I think we will and I think we're going to be screening for everything, which is that good? Is that bad? Do you want to know that you're going to have something, the insurance issues play into that? I think where I see the most patients right now, and I think what's surprising is by the time people are in their mid 80s, there's a large percentage of patients who have an abnormal protein in their blood. And the question really is that going to turn into something that we have to deal with or not deal with? I do think what's really important and where people are really lucky is if they have a good primary care doctor or they go to see a rheumatologist or they have a kidney doctor because they're dealing with some other issues and they get screened for myeloma, I think that ends up being the most impactful because then we can pick up on those patients who do need treatment sooner. But to answer your question, I think we're going to get screened for a lot of things that I don't know that we want to know about it that early.
Dr. Joseph Mikhael:
And between now and then, what do you think we can do to try and hasten the diagnosis of multiple myeloma? I know that's a massive question, but let me just ask the crowd for a minute. How many people here, if you're comfortable answering, you put up your hand, you don't have to, but how many people who have multiple myeloma would say that it took, and I'll be a bit vague, it took several months to figure out that they had multiple myeloma? Wow.
Dr. Tara Gregory:
Yeah.
Dr. Joseph Mikhael:
The average, and different places are different, but there was a very, I think, important study in the UK where you think actually the timing may have been more rapid because of their public healthcare system, but the average myeloma patient sees their primary care provider three times with signs and symptoms consistent with myeloma before the concept of myeloma gets triggered and the blood tests and whatever else is done, x-rays to confirm multiple myelomas. I'll share with you a little later today, that's even longer in the African American and Latino American populations for lots of reasons. Heather made reference earlier to the importance of health equity, and we'll come back to that. But what can we do now to try... We're not quite the stage of screening yet. We don't want to wait, as we discussed yesterday, for people to get the CRAB criteria. How do we catch them earlier?
Dr. Tara Gregory:
Well, and I think one of our responsibilities as myeloma doctors and something that we're doing in Denver is we are really trying to work our way into the primary care network, starting in the Denver area, seeing how that works, and then expanding out to Colorado. How can we go out and educate those primary care providers, the nurse practitioners, the PAs and the doctors to say nobody needs a creatinine of two or dialysis to find out they have myeloma. Maybe think about when the kidneys are looking a little off that that's the time to send the SPEP. It's not normal to have somebody, it doesn't matter how old you get, it's not normal to be anemic. And it's surprising how many providers think as you age, it's okay to have your red blood cells drop, and it's not.
And so if we can go out and start to educate, if things are starting to change or look different, it's okay to send an SPEP or if you don't know, you can send the patient to us and we're happy to help work it out. So I think it's going in and educating our peers really about the disease.
Dr. Joseph Mikhael:
And it's amazing what this crowd can do as well. In your own advocacy, Danielle yesterday spoke to us about advocacy in advocating for awareness of the condition. I'll share with you a little bit later what we've been doing through our Empower program to have the lay public also understand. I don't want people to be obsessed about myeloma. I don't want everybody who has back pain to think they have myeloma. Obviously we don't want to go to that extreme, but at the same time, I think we all have a responsibility in raising that awareness and advocating for ways. Thankfully, some of the early barriers of primary care, there was a time where primary care doctors were not allowed to order a free light chain assay, that it was only given to experts. And so those kinds of things we're trying to navigate.
All right, that was kind of just a warmup, a little feel good. We all kind of agree about things. We are later going to have controversies when doctors Lee and Vescio get up to the stage. That's where you're going to see some fists swinging and so on. So I'm trying to keep this a bit more genteel, but you did say in your introductory statement that you had been interested in transplant. And so my question two for you, question one was, will we be screening for myeloma? Question two for you is, do you really think in let's say five to seven to 10 years now-
Dr. Tara Gregory:
Three years.
Dr. Joseph Mikhael:
... we're still going to be doing stem cell transplants?
Dr. Tara Gregory:
No, and I hope not. I really hope not.
Dr. Joseph Mikhael:
Most people don't commit to that so well. So this is great. So I mean, I don't know if Dr. Lee and Dr. Vescio are going to get in on this fight later, but okay. So tell me why do you think we're going to be giving up on transplant?
Dr. Tara Gregory:
Because I think immunotherapy is the way that we're going. Getting our immune systems involved in fighting off cancer is going to be the way we do it. And we have drugs that can do that. And even though modifying T-cells is considered a drug, we think of that as a cellular therapy, and those are going to change a lot too. But these responses, yesterday you touched on minimal residual disease and how long in the right patient do you stay low or negative with your minimal residual disease to say, "I don't need treatment anymore and I'm cured." And so that was really exciting. In February, we have a definition of myeloma cure this past year, which is just fantastic.
Dr. Joseph Mikhael:
And we'll come back to cure. That's question number four. So what about now with transplant then? If we think that something may change in the future, I think, okay, maybe someday I'll go get a new iPhone. I'll have the iPhone 76 or whatever they're at now, but I'm still pretty old on my phone. But in the interim, is there still a place for transplant right now?
Dr. Tara Gregory:
So the standard of care is still transplant. So I think when we think about our patients and we put a myeloma patient in our brain as a provider, we think, okay, this is my patient who's newly diagnosed. This is the patient who's early in their treatment. They've seen no treatment or one treatment. And I mean, a lot of people in this room have badges that they say they had a stem cell transplant and they're still on maintenance therapy. Are there any of you guys? Yeah. That's amazing, right? You got a treatment and it's been lasting for seven years. So when you think about that kind of person, and we call that an early myeloma patient, that's a lot of treatment you got under your belt. And then we think about the patients who've had myeloma and they've been through a lot of different treatments. And so we call those our late patients.
And so I think what's really fascinating is that we have these drugs in our late patients where our patients who've been on treatments A, B, C, D, E, weren't supposed to respond to anything else. And now we're getting these deep remissions and it's just really fantastic. So when I think about a transplant, all I had to offer somebody with late disease was a second transplant. And when we look at our numbers in Colorado, I think we've done maybe one or two second or late transplants for patients because the stuff is so good. So those are going away, which is kind of freaking the hospital out because they're like, "How are we going to make money?" So then you think about the patient who's the newly diagnosed. And so the standard is you give treatment, you do the transplant, you do maintenance. Well, in somebody who's younger, I want to use all the tools in my tool belt because they've got to live a really long time, like 40 plus more years with this disease.
So I want to make sure I'm using everything. But if somebody's in their mid-seventies, do I really need to go pummeling them with massive doses of chemotherapy when if the first thing doesn't work out, the second thing is so great with these bispecifics and these drugs that I can give people? So I do notice in the last year, patients are electing not to do a transplant because they know that option two is really, really good. So what we're doing in Colorado is we are opening a lot of clinical trials that are saying the study gets to decide. You guys talked about studies yesterday. So that's called a randomization and everybody collects their stem cells and puts them in the freezer. And this group gets a transplant and this group gets a drug for 18 months or this group gets a CAR T, and we're going to see what ends up happening with that. But I think those are the therapies that are going to show us that transplants are going to go by the wayside.
Dr. Joseph Mikhael:
Wow.
Dr. Tara Gregory:
That's a long answer.
Dr. Joseph Mikhael:
You heard it here first, right? That's really fascinating. And I agree with you. I think what's fascinating to me is that even though we always say you're the champ until someone knocks you out and practice will not change until those trials prove unequivocally that CAR T or bispecifics are superior to transplant, I think the knowledge that those are available later are swaying some people away from transplant. And I think the take home message for you today for those, because I know we had quite a number of patients who were early on in their disease course yesterday who put up their hands, it's not just as simple as yes to transplant or no to transplant. It really is worthy of a conversation. I know we've repeated this over and over and Mary is going to talk a little bit more explicitly about this when she gives her lecture about this concept of shared decision making and just how important it is to really decide.
Because sometimes people have this idea that there is this sort of, I want the best therapy, but is there really the best for you is not just one thing, right? I sometimes use the analogy because I always use analogies of food, is that what is the best thing on the menu? Well, it depends who you ask. My wife might choose one thing, I may choose another, our daughters may choose something else, and it still actually may be the best for each of us. You ask your waiter or waitress, what's the best thing on the menu? So we've reached a point in myeloma where some of you heard me joke about this before. I feel like we have the Cheesecake Factory menu, right? It's ridiculous. You need a table of contents to go to that place because there's just so many things on the menu, and we're blessed by that. We're blessed by the fact that we have those options.
And so deciding on the option is not just as simple as thou shall to take a transplant to saying, "Okay, is the transplant the right thing for me?" I like the way you put it because often I say to my patients, I could do a transplant, but should I do a transplant? Because we know that transplant does come with certain key side effects and it does take people out of work or out of their daily routine for at least a few months and has some consequences down the line. Well, let's come to question number three about the future. We're going to spend a little bit more time and then we can open up for questions.
Yesterday, I think you may have been there when I talked just a little bit about the future of myeloma, just to sort of wet the appetite and I talked about in vivo CAR T and trispecifics and allo CAR T. Again, in your crystal ball looking to the future, do you think that we will be moving towards this kind of next generation of CAR Ts and bispecifics and antibody drug conjugates? Do you think those are going to really supplant what we're doing now? Is it really going to be much more about trispecifics than bispecifics? Is it going to be more about this new modality of CAR T than the one we have now? Or really are the tools that we're using now going to be the ones we're going to use in the long term?
Dr. Tara Gregory:
I think they're going to be new tools. And I have the benefit in my practice is we do all different kinds of blood cancers. So whereas I focus on myeloma, I go to an outreach clinic where I meet patients. So I have to take care of all kinds of things like acute lymphoblastic leukemia and AML and MDS and all those kind of deals. And so I have the benefit of watching what's happening with acute lymphoblastic leukemia, and they are a little bit ahead of us in the myeloma world. And really what's exciting is there is a drug called Blinatumomab and it works a lot like our Teclistamab, and we kind of copied ALL for that disease and the Blina. And now people are getting an injection of a medication and then the patients start making their own Blinatumomab in their own livers, which is super cool.
And just a couple years ago, they were going home on a pump that was pumping that medication into them 24/7 for 28 days straight. CAR-T started with our ALL partners, and so we've copied them there. It just took a while to find BCMA in our target. So I do think that all those things are changing because it's hard. It's expensive to go get a patient, bring them to Denver, get their T-cells collected, ship them off, bring them back. There's a lot of logistics there. And so if we can do therapies that meet patients where they are, then that's the best way to go. I mean, because in Colorado, you have to cross how many passes, and are they going to be closed because it's snowing? And my patient's a rancher and so he wants to be out with his herd of cattle.
So there's different things that you deal with geographically with your patient populations. And so trying to get those therapies out to patients instead of making them come into a hub center, I think that's where the new therapies are going to lead us.
Dr. Joseph Mikhael:
I mean, it is really so exciting as we shared it yesterday. And I think the take home message for the group here is one, amazing hope for the future. There is no doubt that we are getting better at treating this disease with these great treatments that we have. The clinical trials are so relevant because as we shared yesterday, clinical trials are not only for the Hail Mary pass, as I said, when everything else has been used, that very often you can get access to these earlier treatments through the process of clinical trials. We have multiple institutions represented here. We shared with you yesterday the search engine we have on myeloma.org at SparkCures where you can look for clinical trials that are relevant to you and you can even look if they're close to you. And also I think it allows us to remind ourselves of how important it is to stay attuned to what's happening in the myeloma world.
So it brings hope, it gives you opportunity for clinical trials, but it also reminds us how important it is to be informed. Things are changing so rapidly. I don't know how the general oncologists keep up with-
Dr. Tara Gregory:
I don't know how they do it.
Dr. Joseph Mikhael:
... 30 or 40 different tumor types. I've just got one and I'm trying to keep up with all that we have in multiple myeloma, but that's an encouragement to you. First of all, it's a thank you for being here today. It's a commendation to you for taking ownership of your own disease to learn about it. But being in the know, keeping up to date with those videos that we talked about, with these seminars, with the virtual seminars, this is really important because these could be the treatments that will allow you to live longer and to live better. And I think what excites me about a lot of these new treatments, Tara, as you've noticed, using the example of lymphoblastic leukemia, and I think in the past of how many patients I used to take to allo transplant for that disease.
Dr. Tara Gregory:
I know.
Dr. Joseph Mikhael:
This was a really, really challenging treatment where up to 20% of our patients died just from the treatment, let alone the disease, that now we can see people living better and longer. And so whether it's an in vivo CAR T or a trispecific or an allo CAR T, all those things we described yesterday, one of those things may be in your very future and you may be one of the patients that could really benefit from that. Well, my last question for you before we open it up for Q&A is really, again, on the optimistic side. You mentioned it, I mentioned it briefly yesterday, that for the first time, although we're not claiming mission accomplished as it were, we're not saying we've cured myeloma, but we're starting to use the term. We're starting to understand it, there's that sort of average Joe. As I said yesterday, when your name's Joe, you can say that, right?
The average Joe that you would ask on the street what their definition of cure would be, which they probably say something like, "Well, you get treated and then you stop treatment, you don't have to think about the disease anymore." But then we have to have a more clinical definition as we design clinical trials that can prove or demonstrate if certain patients can get into a cure. And the working definition we have is essentially that someone gets treated, they stop treatment, they've achieved that MRD negativity and they stay in it for five years off of treatment. And as you mentioned, we have some patients from a clinical trial with CARVYKTI, one of the CAR Ts that we use, where patients were treated with multiple prior lines of therapy and a third of them meet that definition essentially where five years later they're still off treatment and they're MRD-negative.
Dr. Tara Gregory:
Right. I had some of them in my clinic and they said, "I'm cured." And I was like, "Oh, let's not say that word." And then here they are just doing amazing and meeting that definition now, which is really exciting.
Dr. Joseph Mikhael:
And that's the question for you is do you think we will cure myeloma? Do you think we will have at least a so-called functional cure where patients may still have to get testing and can't forget about the disease like that average Joe definition, but that they may remain off treatment for long periods of time?
Dr. Tara Gregory:
I do think that's the case. And I tell patients and I meet a lot of my patients, I'm like, "My goal for you is to live with myeloma and not die from it." That's what I was saying up to a year ago to patients. That is my expectation. Things are changing so fast. We use one therapy, it gets you this longevity so that we can get to the next thing because the research is happening, because Jeff Mattis says, "The next best treatment is available to you on a clinical trial." That's like a Jeff-ism. But I really do think we're going to get there with the population of patients. Now, you mentioned this functional cure and we have other patients that just don't behave well and we call them functionally high risk. Everything on paper says that they should have these long remissions and do really great, but it's not the way that their myeloma behaves.
And so we call those our functionally high risk patients and I still worry about them. I think we're going to be able to get them more time is what I see right now. But I think with those standard risk patients, I think we definitely are going to start seeing more cures in the myeloma space.
Dr. Joseph Mikhael:
That's so exciting. And I think I completely agree with you. And we balance the optimism with realism. I always say I'm an optimistic realist. The optimistic part of me with the privilege of the roles that I have is to be able to see the myeloma community at large and see all these trials, see so many patients like those in your clinic that you described who are doing really well. But I balance that with the realism is that we also do talk to patients that have forms of myeloma that are very terrible. I'm just being honest with you, right? That there is a spectrum. One of the things we like to teach at these sessions is it's hard to go and meet someone and start comparing together. In one way, it's good. Heather made reference to support groups and how it is good to share that experience.
But at the break that we're going to have in a couple of minutes, you don't sort of go up to someone and say, "Hey, how high is your light chain?" You don't necessarily compare that because it can be very different. We still have, and I suspect that that number thankfully is shrinking, but there's still a small fraction of patients, whether they have the definition of high risk or are sort of functionally high risk, meaning that they don't have the high risk features that we define, but they're basically behaving like high risk. I've often used the example of the car, that high risk is like having the sports car. You look at it, we see, oh, the definition I showed you yesterday, that person has the p53 deletion or the p53 mutation. I know unfortunately that disease is going to drive quickly, but sometimes we don't see any of those things, but the Prius still drives quickly.
And so when we look at that group of patients, we have to be very cautious. That being said, again, this is a commercial for our virtual workshop coming up in a couple of weeks. We're going to specifically be looking at that issue of high risk myeloma and how some of these newer therapies are starting to overcome that difference between high risk and standard risk multiple myeloma. But I want you to leave very optimistic from this session, that Dr. Gregory has told us that in the future we should be able to catch myeloma earlier, that we will probably be doing very few, if any, stem cell transplants, that this next generation of immunotherapy is going to be even better than what we have now and that we will be curing a significant fraction of patients with multiple myeloma.
But we still have at least 15 minutes left in the session, so we're right on time. I'm going to ask our team to bring the mics out. And if you have questions for Dr. Gregory, please, this is the time to raise them. So if you have a question, put your hand up and we'll come running to you. Christina, it looks like we've got you right there.
Christina:
Okay. This is for probably Dr. Gregory. She is my myeloma specialist that I love from Colorado. Go team. I've been on maintenance now nearing three years on Revlimid and some different treatments. I am considering that transition to take a break. I know I should do that carefully. What tests, other than MRD through a bone marrow biopsy and a PET scan, should we evaluate whether that's a wise choice or not?
Dr. Tara Gregory:
That's a great question. So the question for everybody is, if you're a patient who's had a stem cell transplant and you're on maintenance, can you stop maintenance and how do you make that decision? And I bet that's going to be one of our controversies today.
Dr. Joseph Mikhael:
It is one of the controversy questions. Yeah.
Dr. Tara Gregory:
So Dr. Lee, I hope she doesn't come hit me since we're going to fight. But in our practice, we are recommending that people stop maintenance. And we're extrapolating from, I think you guys talked about the ENDEAVOR trial yesterday.
Dr. Joseph Mikhael:
ENDURANCE, yeah.
Dr. Tara Gregory:
ENDURANCE, sorry. So ENDURANCE, what happened is that those weren't patients who got transplants. Those are patients who opted for non-transplant therapy and then they stopped maintenance. And really it didn't look like there was a ton of benefit after about two years. The survivals looked good between the two groups. And so we are kind of comparing apples to oranges a little bit, which you're not really supposed to do in medicine, cross-trial comparisons, but we're saying, "Okay, well, if you look at the history of transplant versus non-transplant, transplant typically made things better." So if you have a study with non-transplant that says you can stop, then A plus B equals C. So what we're doing in our standard risk patients, not our high risk, is we're recommending that patients go ahead and they get a bone marrow biopsy to assess their MRD status. And if they're MRD-negative, then we're sitting down and having a conversation and a PET/CT about stopping therapy and then their other labs.
Now, we're taking that a step further to say, "Well, what if I'm not MRD-negative? And what if my M spike is still 0.1 and it really is my myeloma, but I'm having horrible side effects and I've been on treatment for a while." We're saying, "You know what? In that situation, you should probably go ahead and stop too because you have to have quality of life." And we don't want to see patients get terrible neuropathy and we don't want patients having diarrhea where... I mean, I've had patients are like, "Well, I took two packets of cholestyramine and loaded up on Imodium so I could go to Costco for two hours because I just can't be that far away from the bathroom." And that's not a way to live.
And so if you have these therapies that are so good and an option for you when you absolutely need them and your doctor's going to watch you really closely and make sure that you're not going to break a bone and you're not going to end up on dialysis before they catch it and do something different, then that's probably a reason to stop too. So we're having those conversations with patients because we have such good options. It used to be we're like, "Oh no, you can't stop because I don't know what I'm going to do with you if you stop and your disease comes back." But now that's different.
Dr. Joseph Mikhael:
Yeah, and I agree. I mean, I think that ENDURANCE trial was so helpful. And the ENDURANCE trial really did not use MRD as a marker because it was designed and done a day before that was done. And now that we have more access to MRD testing, and I know this will always come up in questions, so I'm sure it'll come up later, but right now probably the most reliable way we do MRD testing is on marrow, but there are tests being developed and being used where we can use someone's peripheral blood where it's a blood test as opposed to a marrow test. And I do think with time, those two used in conjunction together can be helpful to us to save us from getting that needle in your backside every time we want to check for it. So I completely agree. Okay, next question is over here, Nikki.
Nikki:
Hi. First of all, thank you for sharing all of your knowledge with us. It's really a blessing to be here, so I appreciate your time. We are new to the myeloma world. My dad was diagnosed the end of last year and he was really on the cusp. It was kind of a tough call for the doctor at the moment. It really resulted in my dad making the decision to proceed forward with treatment based on the fact that he just didn't want to feel the pain that his physician had explained would come about if he didn't take care of this myeloma. That being said, he entered into the MajesTEC-7 clinical trial.
Dr. Tara Gregory:
Very cool.
Nikki:
The arm he pulled was not the arm that I preferred, but it was what it was and he experienced several side effects from that. They have stopped and administered the treatment twice on this specific drug. He's been on the Revlimid and the Daratumumab, but my concern is the sponsor is wanting him to try the drug one more time. He's had a hospitalization in the middle of all of this. Not to say that it was specific to the drug that he's on, but it was enough that it was a five-day hospitalization. So as a daughter and a caregiver, I'm very concerned about him starting this drug again, considering the fact that he's just had negative impacts. The side effects have not been fun.
So that being said, he wants to try it a third time. He's very stubborn, doesn't like giving up, but if that doesn't work for him, he is responding well so far to the treatments just in general from a number standpoint. They're pleased with what they're seeing, but if he doesn't continue on this clinical trial, or do they even keep him in the trial if the one drug they're trying to really administer is not working for him? Does he necessarily leave the clinical trial? And if he does, is he eligible for any other clinical trials? Just not sure since this is all so new and overwhelming.
Dr. Tara Gregory:
Okay, so that's a lot.
Nikki:
Yeah, sorry. I'm a lot.
Dr. Tara Gregory:
No, that's good. So here's what I heard. I heard that your father is newly diagnosed and he got involved in a study and the study basically is looking at giving these bispecifics to a newly diagnosed patient, which is where we think this is going. And he's having side effects. And the question is what to do with the side effects. The second, and do you keep trying? So some comments there. I think the second piece of the question is, does this make him ineligible for other studies? So the first part is the interesting thing about immune cells is they release your T-cells. In my world and what I explain to my patients is that your immune system is a bunch of female superheroes, specifically female superheroes. I'm the only female physician in my group-
Dr. Joseph Mikhael:
Not saying a word.
Dr. Tara Gregory:
I don't know why, but in my world, female superheroes, when you think about Wonder Woman, Captain Marvel, they create some damage on their way in. And so they're releasing these inflammatory proteins is what T-cells do. That's how they kill cancer. And so these cytokines are like little poisons to the cancer cell. Well, when you get sick and your T-cells are active and you have a fever and you have a cough and you're hot and you're sweaty, those are cytokines doing that to you. So you can imagine the more those T-cells see cancer, the more cytokines they're going to release and the more side effects you're going to have of fevers and low blood pressure and reactions. So part of me wonders, did he have so much disease that his immune system just got super excited and then he had more of a reaction?
And we are learning that with CAR T-cells that we used to think you can go into CAR T and just hit it and it didn't matter how much cancer you have, but now we're like, oh no, actually it's real important to get that cancer beat down as low as you can get it before you get the CAR T so you can avoid the side effects. So we do see that with the bispecifics. The more disease you have, the more of a reaction you're going to have. So maybe with him, because he's responding to the other drugs and his myeloma is going down, then there's a chance that he'll have less of a reaction. You can pre-medicate more. One of the things that can happen is you can ask special permission to the study to give a drug that blocks one of those inflammatory proteins called IL-6.
And the drug is called Tocilizumab. So sometimes you get special permission to say, "Can we give that so that we can avoid the reaction in general?" So those would be some of the things about the study and maybe it'll go better the third time around because it is scary to watch somebody go in the hospital because it's essentially like instant sepsis. It's like you get really sick. The second piece of the question, is he eligible for other clinical trials? And the answer is yes. There are a lot of studies that say we want a patient who's had anti-BCMA therapy because we want to show that ours can get that person under control even if they already had treatment that targeted that drug or that receptor. So definitely there are a lot of times clinical studies only want you when your disease is getting worse and we call that relapsed and/or refractory. So he might have to wait, but generally speaking, yes, he'll be a candidate for other clinical trials.
Dr. Joseph Mikhael:
Beautiful.
Dr. Tara Gregory:
Final answer.
Dr. Joseph Mikhael:
Next question. We'll come over here to Danielle.
Danielle:
News that Iberdomide just got FDA approved.
Dr. Tara Gregory:
Finally.
Danielle:
And so I am wondering where you see the placement of Iberdomide and Mezigdomide coming up. Also, since it has a lower profile of side effects, how do you see that possibly replacing a drug that someone's being treated on and that's giving that person side effects?
Dr. Tara Gregory:
Right. So the question is about a new type of drug called CELMoDs and one just got FDA-approved and we've been waiting for what, 10 years? It's been a long time. And the first one is called Iberdomide, And so we call that one Iber, and then the other one is Mezigdomide, and we call that one Mezi. So those drugs, what happens with your Revlimid or lenalidomide, and I always tell patients, Revlimid gets its name because it revs up the immune system, if you kind of think about that, Revlimid. And Revlimid does a bunch of things. First thing it does is it gives you extra female superheroes so that they can fight off your cancer. So it revs up your immune system, but it also helps kill the myeloma cell because it blocks a protein called Cereblon. So it's a Cereblon inhibitor. So what these drugs are is these drugs focus specifically on Cereblon.
And so we think we're going to see less low blood counts, rash issues, secondary cancers go down. So largely I think as a myeloma community, we think, to answer one of your questions, that the Cereblon inhibitors will probably go ahead and replace drugs like Lenalidomide, Pomalidomide, Thalidomide, just like we very rarely use Thalidomide anymore. It's still around. Sometimes you got to pull it out because you are trying to get different effects of the drug. So I think those drugs will be out, but I think eventually you'll see the cell mods replace. And I think where we're going to start to clinically see it first is going to be in more of the maintenance setting. I don't know, what do you think?
Dr. Joseph Mikhael:
No, I agree. I mean, I go back to the Cheesecake Factory menu. I go back to their patients that in the relapse setting, maybe they've already had a CAR T or a bispecific or are not eligible for a CAR T or prefer to have a more easily delivered pill that they take at home. In the approval, the initial combination would be the Iber, the Iberdomide as a pill, and the Darzalex, which we use quite routinely now subcutaneously, initially every week, then every other week, then only once a month. So a lot of these patients I think who are going to be eligible are ones that may not wish to or may not be candidates for the more intensive regimens of CAR T or bispecifics. But I think we're going to just again add another page to that menu where we have more and more options.
I do think with time we're going to see Iberdomide tend to replace Lenalidomide and Mezigdomide tend to replace Pomalidomide, but that'll take a longer period of time. Okay. We have time for a couple more questions at least. Okay. Simon has got one over here.
Simon:
Thank you for your expertise. So the question that I have is, so therapeutic sequencing, so you're diagnosed, and how much of this is like playing chess where you're trying to figure out, okay, so I'm going to have CAR T versus bispecific. And is that a thought process? How does that work? Because maybe you're not eligible for a certain treatment if you have something. And so I think, is there some complexity there?
Dr. Tara Gregory:
Right. So I think the question is you have all these options. How does the doctor pick or how does a patient advocate for themselves to get the right thing? And I think Dr. Joe did say the right thing is different for different people. I do think generally speaking, as a myeloma doctor, I want to get my patients access to immune therapies to fight off their cancer as soon as possible. That's where we see the deepest responses and if you have the deepest response and you know people who have deep responses are the people who live the longest because we have to wait a long time to see what's going to happen with these studies, how long people are going to live. But if the deeper response translates into better survival, then that's what I want my patients to get to. And then I have to think about, but my patient, what's safe? What can they do? What's manageable for them?
So for some people, they want a one and done. They want the CAR T, they're willing to come deal with it in Denver for a month and then go home and they don't want to have to take anything and they just want to be out on the ranch doing their thing. And other people, it's, "Well, I've got some heart issues and I'm not as mobile and the CAR T therapy sounds a little scary," because these people get something like Parkinson's and that's terrifying and I'm not that kind of risk-taker, so I'd rather do the antibody treatment. But I think generally speaking, to answer your question, in my practice at least, our goal in terms of sequencing is how fast can I get you a bispecific or a CAR T, and I'm going to put patients on clinical trials every time to get them access to that faster.
Dr. Joseph Mikhael:
Yeah, I think you said it beautifully. I think the only thing I would add is there was a day when I think we thought you had a choice of three bridges. Are you going to walk down the CAR T bridge, the bispecific antibody bridge, or the antibody drug conjugate bridge, and that was it. You had to choose one of the three. But I think we're learning now that in fact, a lot of patients end up getting all three. So there is a lot of crossover able. We can do a lot of crossover later. We have time for one last, hopefully relatively short question from Christina.
Christina:
Thank you both for being here and sharing your expertise. I was just diagnosed about a year and a half ago. I have gain 1q21 with four copies, deletion 1P, CDK, and 2C loss. And I have concurrent CLL, which seems to make me ineligible for trials. On top of that, about five months ago, I developed an EMD on my chest. So they took care of that and basically stopped the VRd plus Dara and I just had a CAR T cell transplant a few months ago. I'm doing okay now. But given all of that, a lot of us are here for hope. I certainly am. What reasonable treatments can I pin my hopes on? Not the farfetched stuff, but is there something coming up for me that, because eventually the CAR T will probably stop working. What am I going to do then?
Dr. Tara Gregory:
That's a good question. So the question is really, I have myeloma and something else and I'm dealing with both and what else is going to be out there for me? In your specific situation or in people who have myeloma plus something that's kind of a cousin disease like Waldenstrom CLL, we're lucky in that there are some targets that are on both. And a lot of those therapies are starting to come where we're saying, okay, let's grab CD19, which we see on B-cells. The thought being, if you have a B-cell turn into a plasma cell, maybe we can grab some of those other myeloma cells that are kind of in evolution. But in somebody like you, if you can grab CD19 and BCMA together, then you're kind of getting a twofer.
So I do think that those therapies that have in the antibodies that have two targets, one plus two, and then they grab a T cell, we call those trispecifics because there's three things. You're going to start to see drugs or CAR-Ts that are going to hit both. I think that would be reasonable for you. And a lot of our drugs against myeloma do work against CLL as well. It's not terribly uncommon to see patients with myeloma have a little underlying CLL and do quite well from the CLL perspective.
Dr. Joseph Mikhael:
So I would be optimistic because I think very often we find this with patients that may have more than one condition, often one goes quiet while the other one is active. And so apart from being limited in certain clinical trials, all the other things, the bispecifics, the trispecifics, potentially allo CAR T, in vivo, all these things should be available to you as well down the line. Well, I know we can answer questions all day long and we will come back to questions, but it's time to take a break. Let's just quickly thank Dr. Gregory for joining us.
Dr. Tara Gregory:
Thank you. Thanks for having me.
Dr. Joseph Mikhael:
And she and I are just going to sit here and have a little fireside chat. I don't think we'll start a fire considering how warm and humid it is already.
Dr. Tara Gregory:
Yeah, where's our fire?