Replay the Facebook Live Event

Dr. Joseph Mikhael (00:16):

Hello and welcome, everybody. This is Dr. Joseph Mikhael. I'm the chief medical officer of the International Myeloma Foundation, and you have made it to the Facebook Live event that we have been promoting over several weeks now, that we've entitled, Ask Me Anything. Now, when we say, "Anything," and I saw some of the comments around it, when I said, "Anything," let's try and keep it about multiple myeloma, all right? That's the plan today is to spend the next half hour together thinking about myeloma. I've had the privilege of being involved in myeloma for over 25 years now. And I don't know if we've ever had a more exciting time than right now in myeloma, as we develop these new therapies, as people thankfully on the whole are living longer and very often living better lives with less treatment or treatments that are easier on the system. And so, with all of that happening, there's still so many questions that come up about new diagnostics, and new treatments, and, "How do I face this disease? And with whom can I face this disease? And, how long do I need to take this therapy?"
(01:24):

So I'm going to do my very best over the next 30 minutes to answer a lot of questions, because one of the things that the IMF believes in and has believed in for over 30 years is the value of the patient's voice, that you should have a voice, that you should be able to ask questions of your healthcare practitioner, that you should be able to ask questions in the right venue. And one of the ways we've tried to do this, not just here today in, excuse me, this Facebook Live, but is through a whole series of activities that we host over the course of the year. Our sentinel activity is what we call a patient and family seminar, and if you're not familiar with a patient and family seminar, you should get aware of it.
(02:08):

If you happen to be around or want to be around the Los Angeles area, August 18th and 19th, we're hosting our next patient family seminar there, where a lot of the same kinds of questions that I'm addressing today you have the opportunity to ask of the experts. And it's going to be hosted by the chair of our board and our chief scientific officer, Dr. Brian Durie. But joining him will be a whole series of extraordinary physicians like Doctors Abanuor, and Raje, and Visceo, as well as a member of our nurse leadership board team, Donna Catamero, where we'll be able to dig deep into multiple myeloma.
(02:44):

And so, if you have the ability to join us in Los Angeles next month, please do so. If not, as we're going to be dropping in the chat box here shortly, we're going to see that there are multiple other educational programs over the course of the year. Things like, the regional community workshops that we host. We host workshops that are focused within the African American community that we call Empower workshops. And if you go to events.myeloma.org, you can learn a lot more about that. So, feel free now as we get to rolling here in a few minutes to start sending in your questions. I want to thank the people that have already sent their questions in, because there's a lot of them, and I got to try to start working through them very quickly over the next little while.
 

(03:44):
I should make one caveat, of course I always do, which is that, although I practice and take care of patients, I am not your practitioner. And so, it's hard for me to get into every detail of every question. And so, we do very much encourage people as we do provide resources and information to you to follow that up with your healthcare provider, your myeloma physician, or your oncologist, someone on your medical team who can dive into these things a little bit more with you. So, let's get to some of these great questions that are being asked, because there are many of them. And so, let's get rolling with the questions.
 

(04:26):
So, one of the questions that came up that came in, and there are as I say, so many of them, but one of them has to do with maintenance therapy. And this is something that I want to address, because it really is a hot topic, where the person said, "I have a question. What is the best duration of maintenance therapy?" So, to be clear very quickly, when we use the word maintenance therapy, we typically are referring to people that have had some initial treatment for their myeloma, then an autologous stem cell transplant, and then we give them so-called maintenance to maintain the response that they've had thus far.
 

(05:07):
We know thankfully, over 90% of people when they get their initial treatment in a transplant get into a rather deep remission. We know that we don't cure myeloma per se, and so the disease can come back. So we think of it as going into remission, not cure, but it can go into remission for a long period of time. That period of time can be extended by maintenance therapy. And typically, we use lenalidomide maintenance as one of the drugs that we have in myeloma, known from its trade name as Revlimid. And, we know that when we give that, when compared to giving nothing, that it can keep people in remission for longer periods of time.
 

(05:46):
Interesting, this question is asked right now, because just in the last few months our colleagues from England, from the UK, had been doing a large study looking at really how long should we be staying on maintenance therapy, because in some centers they'd go out to about two years, but others, and typically here in the United States, we give it until the disease wakes up. And what this study showed was that staying on maintenance therapy in the longer term beyond four years even still had a benefit. Now of course, we always have to balance this with the potential side effects that people have from maintenance. So, if people are having side effects that can happen with lenalidomide, they need to discuss this with their provider. But typically, if people are tolerating the therapy well, we will generally speaking, give maintenance therapy until such time as the disease wakes up.
 

(06:37):
All right. Here's another question where someone says that they were diagnosed just over the last two months and I'm sorry to hear that that happened so recently, but I trust that your care is going well, and this person is being treated with Revlimid, with Velcade, and with dexamethasone, what's called the RVD regimen. And unfortunately, has experienced some really low blood counts and has had to have some blood transfusions. And, is asking what suggestions or what I can suggest. Well obviously, it's going to depend on circumstances, but I wanted to address this question.
 

(07:18):
Even in my clinic here today, I was having a conversation with a patient around this same notion that we can see very low blood counts in multiple myeloma. Meaning that, we think of the good blood cells that our bone marrow makes. I've joked sometimes to make it simple that makes white, red, and rose, white blood cells, red blood cells, and platelet cells. Red blood cells carry oxygen. White blood cells are our immune system. And platelets are the ones that help us clot so that we don't bleed. Those counts can be low from treatment, but more often not in myeloma it's also low because those blood counts are made in the factory of our blood, in our bone marrow, and that's where myeloma lives. So sometimes myeloma can crowd out the marrow and not be able to allow us to make good cells. But as we treat myeloma and get rid of those bad myeloma cells, the good bone marrow cells can grow back.
 

(08:20):
It's like saying my lawn has got a lot of weeds in it, but as I treat the weeds or get rid of the weeds, the good grass can fill in. And so, sometimes people need transfusion, sometimes they need what we call growth factors or drugs to boost the growth. But ultimately, typically our cells will come back up as we respond to myeloma treatment. Okay. So, here come more and more questions. Let me get moving along here. Here's a great question that someone just asked a few minutes ago, "How do chromosome disorders impact your multiple myeloma treatment and prognosis?" And thank you for this question, Michelle. I think the question that we're directing at is, when we test for myeloma, remember myeloma is a cancer of a certain cell that lives in our bone marrow, called plasma cells, and these are the cells that normally make good antibodies that help us fight off infections. When those myeloma cells become cancerous, unfortunately, instead of producing good antibodies to fight off infections, it produces bad ones that can attack the body.
 

(09:25):
When we evaluate someone's myeloma, we don't just do a bone marrow test and say, "Okay, this is how many myeloma cells you have here." We typically reflect, reflected in a percentage of the total marrow, or someone has at least 10% unfortunately plasma cells to have myeloma. But some people can have 20%, 30%, 40%. I had a patient today in clinic where 100% of his bone marrow, pretty much his whole bone marrow was filled with myeloma sadly. And yet, it's not just about the number. We then can evaluate the chromosomes, the genes of those very plasma cells, because we've learned that although all of myeloma is bad, as it were, we don't like obviously anyone to have myeloma, that certain forms of myeloma can be more aggressive than others. And we typically divide myeloma into two groups, those that have so-called high-risk myeloma, and those who have standard-risk myeloma. And that differentiation is typically made on the basis of those chromosomes.
 

(10:23):
So there are certain things we know are associated with a worse prognosis that we put into that high-risk group. So for example, if people are missing a portion of chromosome number 17 that we sometimes call the 17p deletion, if they have extra copies of a certain part of chromosome 1, what we call 1Q. If they have certain what we call translocations, where two pieces of chromosomes come together like translocation 4;14 or translocation 14;16. All of those things we put into a higher risk category, and it may cause us to treat patients a little bit differently, perhaps more aggressively. By contrast, there are some other chromosomal abnormalities that may portend a better prognosis as we call it, meaning it may be associated with a less aggressive form of myeloma, something called, for example, translocation 11;14. And specifically in that situation, we now have developed drugs that may be specifically helpful for that individual who has that, because when those two pieces of chromosome 11;14 are joined together, it up-regulates a certain pathway that helps the tumor stay alive. And if we can damage that pathway, then the tumor will die.
 

(11:35):
And so, this is why people testing their, what we call, cytogenetics, or looking for cytogenetic abnormalities, or their chromosomes can be really important. So, thank you for that question. It can influence our treatment, absolutely. Here's a great question. It says, "How often should a patient have a bone marrow biopsy if no myeloma adverse events and their blood work is stable?" Thanks Steve for a great question. Every institution does things a little bit differently, but it depends on the patient's circumstances. Typically, the way I say it this way is, look, myeloma is not a simple disease. No disrespect to any other cancer, but sometimes in a lung cancer, I guess, you may just measure the size of it, and it's just one thing that gets followed as it gets shrinking down. Myeloma is more like a crime scene frankly. This is the analogy I use in my clinic as I explain to patients, myeloma's a little bit like a crime scene. What I mean by that is, it's not just one piece of evidence that tells you the story, it's often multiple things.
 

(12:37):
So we look at what does the bone marrow show, what does the M spike show or the big bad protein that we can typically see in myeloma? Sometimes there's a smaller protein that we can also follow myeloma called light chains. And there can be a series of things. We check people's blood counts, we check people's kidney function, we check people's calcium. All of these bits of information point in the direction of is someone's myeloma under control? Are they responding to treatment? And thankfully, most of this can be done by blood work. So we try to do most of our routine follow up of patients in addition to seeing them and talking to them about their signs and symptoms, doing a physical examination, we follow their blood work. But sometimes, we do have to repeat bone marrow tests, either because the blood work doesn't look right, or sometimes there are forms of myeloma where it's hard to follow the myeloma in the blood work.
 

(13:30):
Some centers just say, "Look, once a year we want to check your bone marrow, because that's really where the myeloma is housed, the headquarters of it." I tend not to do a bone marrow just routinely, unless it's part of a clinical trial protocol or something. I typically will do a bone marrow when there's evidence that the disease is regrowing again, as opposed to just doing it repeatedly. Here's another great question, "Are the side effects of lenalidomide cumulative?" That's a great question. And of course, drugs respond differently in different patients, and different patients have different adverse reactions. There are things that are a little bit more common with lenalidomide, people can feel fatigued, people can experience diarrhea, people can experience muscle cramping, it can increase the risk of getting blood clots, and it can increase the risk of infections specifically by dropping white blood cell counts.
 

(14:23):
Generally speaking, it's not so much that we think of them as cumulative, but there is a component to it, as people are on the drug longer term, some of those things, namely the diarrhea, the cramps, and the low blood counts that can pick up over time, meaning that that can get worsened over time. There is also a potential risk of developing another cancer while on lenalidomide. Although, we know that all myeloma patients unfortunately are at risk to some degree of a second cancer, but that can be increased with lenalidomide. So, this is one of the reasons why over time we may have to dose reduce the lenalidomide and sometimes even discontinue it if those side effects continue to be a problem.
 

(15:04):
Wow, lots of questions are really pouring in, so I want to speed up my answers so that I can get to them quickly. Oh my goodness, we've just got a whole wave of them coming in now. "What are the possibilities after Abecma CAR T relapse? So, Abecma or ide-cel is one of the two approved regimens we have for CAR T-cell therapy, where we take T-cells out of patients, manufacture them such that they can recognize their myeloma, and give them back to patients. Thankfully, it's a very, very effective therapy in the majority of patients and it can last a long time. But sadly, most patients still relapse.
 

(15:44):
So we are looking at other options after that. Very often now we look at bispecific antibodies, these drugs that have two arms, that's why they're called bispecifics. They hold on to the myeloma cell, but they also reach out to a local T-cell and engage it. And we are learning that we can use bispecifics after CAR T, like in this question. And sometimes we actually even go to a different CAR T, and we are developing CAR Ts that work differently than these first two CAR Ts that we have. So there are options there. And lastly, we sometimes go back to the traditional therapies. This great question from Beth, there are some therapies that we can go back to, even if someone has had them in the past because they haven't had them for a long period of time.
 

(16:27):
Okay, here comes another question, "How do you test and follow up for transplant for remission when lytic lesions was a qualifying factor?" We do look at bone disease in myeloma. And again, I don't want to oversimplify things, but unfortunately myeloma, when these bad plasma cells grow, they can go and occupy different bones and create little holes. And, as we treat myeloma, we want those holes to fill in again. But sometimes they don't fully fill in or sometimes they leave, if you will, a scar there. And so, it's always very important to be careful how we think of bone disease. Now, with the newer techniques of using PET scans, it has been a little bit more helpful and effective for us to be able to know is this true active bone disease? Is this because there are plasma cells in that bone growing and growing? Or is it just some of the damage that they've left from before? And so, that may be helpful in making that discrimination.
 

(17:29):
And one person says, "I'm post-transplant and on maintenance with Darzalex Faspro, and I'm getting IVIG infusions. My heart rate is dropping into the thirties after infusions. Is this normal?" Again, I think this is something you need to bring to your provider to be more specific. It's not typical that we see that degree of drop. It partly depends on what your baseline heart rate is. People can get reactions to either IVIG or Darzalex. Typically, the Darzalex reactions only happen after the first few doses. So this is something I think should be discussed. The next question, "Should daratumumab dose be scaled to body weight?" When we're giving the drug intravenously, we do. But typically now, that when we give it subcutaneously or in the skin it's a flat dose. There are some situations we make adjustments when people are very light or people may be very heavy. But in general, we don't base on weight the dose of subcutaneous daratumumab.
 

(18:29):
"When do you stop frontline therapy? Based on what labs?" Well, great question, Paul. It depends on which of those labs from the crime scene that I described that speak to your myeloma. And we are learning that if patients, for example, are not going to transplant and they go onto a regimen very often, something like Darzalex or daratumumab, plus lenalidomide or Revlimid, often we've learned that if they're tolerating therapy well, it's actually best to stay on it until the disease wakes up again. Those labs that we follow ensure that we know that the disease is in remission before it wakes up.
 

(19:05):
And so, we are trying to develop stopping rules for myeloma. If there's one thing I'd love to do is give my patients nothing. Right? That's my favorite therapy. I joke and say nada is my favorite drug, meaning, I would love to be able to stop. And we are looking at ways, and this is part of the research agenda of the IMF that Dr. Durie leads in trying to appreciate what we call MRD negativity, or minimal residual disease negativity. Can we get someone to the point where there's so little myeloma left in their body that we don't need to keep treating, that we can stop? And, we're trying to figure out the best scenario to be able to do that, but we're not there just yet.
 

(19:49):
Just joined, "My husband had a transplant in 2020. He's still in complete remission. How long do they use Revlimid maintenance?" I addressed this a little bit earlier in the talk. But I think right now, the best evidence we have is to remain on Revlimid maintenance until such time as a disease comes back. Or of course, if someone is experiencing side effects that they can't tolerate. "Are there any trials that target no treatment when myeloma is stable to limit the terrible side effects of treatment to improve patient's quality of life?" Thank you, Jeff, for this. Absolutely, as I just said, nada is my favorite therapy in many respects. And, I do think one of the benefits, for example, that we see now of CAR T-cell therapy, that when we give CAR T-cell therapy to the majority of our patients now, they get this very intense, but they get this treatment once, and then they go on nothing.
 

(20:41):
Typically, we're not giving maintenance after CAR T. There may be some patients with time in whom we'll develop a protocol for that, but that is absolutely part of our agenda. We would love to have periods of time off of treatment. Every patient would like to be off of treatment. I think of something like hypertension, right? High blood pressure. We haven't cured high blood pressure, and people have to stay on it like myself on blood pressure medication indefinitely. But thankfully, most of the treatments we take don't impact our quality of life. We want to be able to find ways to reduce the burden of treatment that patients have and maybe even stop it in some of them.
 

(21:19):
Here's someone who says that just celebrated 11th anniversary after transplant. Congratulations, [inaudible 00:21:26]. We're very happy for you. "On the third regimen, now on DKD." So daratumumab, carfilzomib, Dex. "But numbers might be creeping up. From your experience, what is the value practically of trying the other leg of Kyprolis regimen KRD?" Well, we know that kyprolis or carfilzomib is a very potent agent, especially if someone has not been treated with it before, which sounds like that may be the situation here. And one of the benefits of the drug is that it can combine quite nicely, either with Revlimid as you've mentioned, or with daratumumab.
 

(21:58):
And so, it really depends on what you've been treated with before, what the disease might be resistant to. But when we look even at our International Myeloma Working Group or IMWG guidelines, we point to those two, amongst others, regimens being very reasonable to choose, depending on what we call lenalidomide resistance, meaning, has the disease ever grown on Revlimid? If so, then probably better to avoid Revlimid. But if not, then it can be used.
 

(22:30):
Here's a great question from Reggie, "Would you say we're at the point of a cure with new age medicine?" I'm cautious to use the word, because I don't want to create false hope. On the other hand, I don't want to shy away from the fact that as I mentioned earlier, 25 years of myeloma, a research that I've been involved with, I've never seen a more exciting time than now. The response rates we're seeing with CAR T-cell therapies, the prolonged response rates from CAR T-cell therapies in these bispecifics, the way that we can now use the immune system to attack a patient's myeloma is really remarkable.
 

(23:09):
And so, I'm cautious, as I say, to use it, because of course the word cure means different things to different people. Cure in my mind means we give a defined treatment to a patient, and then they're truly off treatment, and they don't have to think about the disease again. I'm not sure we're quite on the verge of that. But I think we are controlling the disease much better. We're giving people more quantity and quality of life. And I hope before long we can really start to use the word cure. And that's been the goal of the IMF, and that's truly our mission is to seek a cure for myeloma, and until we seek a cure to support patients and their care partners in the myeloma community throughout.
 

(23:50):
Okay. I have six minutes left and more and more questions coming in. But thank you for all these great questions. Another question says, "My mother's on Pomalyst and doing infusions. And she's been on partial remission for the past few years. How effective would you say the method is?" Well, Reggie, when we think of efficacy of a method, it has partly to do with how deep the response is, meaning how well the numbers go down, how much we've reduced the burden of myeloma, but also how long it lasts. We always think that the deeper means the longer, but some people don't get a very deep remission, but they actually stay in it for a long period of time. So, if someone's been on a treatment that has lasted three years, that's usually a sign that it has actually been controlled well.
 

(24:38):
And someone says, "I've had this for almost 14 years and I still haven't had treatment yet." There are smoldering forms or precursor forms of myeloma, and I'm very excited to hear that, Mackenzie, that you haven't had to have treatment yet. You're still on my favorite drug nada, as I've said. And I really hope that you're able to stay off treatment for even longer period of time. Here's a question from Scott, "Being newly diagnosed, I'm given the option of either the standard four drug regimen, DVRD, versus clinical trial of DRD, not using Velcade. Any comments on this choice?" It's tough. I think you have to look at your individual situation, discuss it with your provider. I think we are seeing that when we combine drugs together, we do see better outcomes, as it were, meaning that people get deeper responses and we are moving towards four drug regimens. But that's not necessarily for absolutely everybody. There's still some context in which we can use three and avoid perhaps some of the toxicity from the fourth drug, in this case, the bortezomib.
 

(25:37):
And so, I do think it is worth having that discussion. It's hard in this context to be much more specific than that. But, we design clinical trials with the patient's best intent at heart to know that we want to be able to give enough drug to control the disease, but not too much. Here's a great question from someone we know, "My husband's blood work looks good with no sign of cancer over two years. Does it make sense to take frequent breaks from Revlimid so the cancer doesn't become resistant to Revlimid?" That's a great question, Tam. We've discussed this in different contexts here at the IMF.
 

(26:12):
It's challenging, because on the one hand, we have learned that there are different ways you can develop resistance. Someone stays on a drug long-term, eventually when the disease wakes up, they're resistant to that disease. But we've also learned that if we expose the disease to a drug, and stop it, and restart it, and stop it, and restart it, and we've done a lot of this work, some great work was done by my colleagues at Mayo Clinic when I was there on this subject, that it can actually breed resistance more quickly.
 

(26:38):
And so, it's a balance. It's hard to know in any one patient exactly how long someone needs to be on treatment. We know that in general, when someone is on treatment, they're going to stay in remission longer, but it's a very tough balance, and I appreciate that question, because it's not a simple one to answer. Here's a question, "Is Velcade the only treatment that causes neuropathy? It's helping my myeloma but causing severe neuropathy?" I'm sorry to hear, Linda, that that's happening to you. It's not the only thing that causes neuropathy. It's probably towards the top of our list. In the old days, we used to use another drug, vincristine that also caused it. But, we can see neuropathy with almost any myeloma drug with the other drugs in that class, carfilzomib, ixazomib, with the immuno obligatory drugs, Revlimid, pomalidomide or Pomalyst. But I do think this is really important to discuss with your provider.
 

(27:27):
We have learned ways to try and reduce it by giving the bortezomib or the Velcade at a lower dose, less frequently. But at some point, we have to stop it, because we don't want to give you irreversible neuropathy. And thankfully, with many of the options we have, we can often do that and switch to something else. Here someone says, "I'm in a biochemical relapse for five years." Wow. "Should I ask for a bone marrow biopsy to see the percent plasma cells or still stay waiting and watching?" It's a great question, Diane.
 

(27:57):
I think, a lot of it has to do with is the test going to change what you do? Meaning, if there really is such a slow biochemical relapse, and we're not ready to pull the trigger yet, is really the percentage of plasma cells in the bone marrow going to change that? More often than not, it might not. Maybe at a point where it's necessary. But, more often not, we'll follow the biochemistry and when we feel that the chemistry is changing... And often sometimes it's a very, very slow incremental rise on a straight line, and then it starts to really curve up and hit that what I call inflection point. And that may be the point where we do the full re-staging of the myeloma. We get the bone marrow test, we get the PET scan to look at it in the bigger picture.
 

(28:41):
Lots of questions, and I'm down to my last minute. Thank you for, by the way, all the kind notes in the box and people joining us from the UK, people joining us from all over. I appreciate all the thank you notes. These are very, very kind. I will note that the IMF has been dropping some links there, how you can contact the info line, how you can register for that patient and family seminar, and the other regional community workshops we carry out over the year.
 

(29:09):
I do want, before I close off, to remind everyone that the IMF has so many different programs and you can learn about it. We think of the four pillars of the IMF in research, in education, in advocacy, and in support. I have the privilege this weekend of going to the National Medical Association, where we as the IMF have partnered with the NMA and the Cobb Institute, which is their research arm to match minority medical students, many from historical black colleges and universities with myeloma doctors to do a project in health disparities. And all those projects are going to be presented this weekend in New Orleans at that annual meeting. And it's just such a privilege to be a part of that as we want to tackle the issue of health equity in the short-term and in the long-term.
 

(29:58):
I have to close off. I want to apologize for some of the questions that I didn't get to. I really tried my best to get through the list. There are so many. But, please reach out to the info line. We're more than happy to try and answer questions that way and do our very best. And please do connect with the IMF, whether it's through a patient family seminar, regional committee workshop, some of the online and virtual programs that we do. I know I'm going to be doing a virtual meeting in September that many of you can join in if you wish. And we'll be doing more of these Facebook Lives. We want to support you, we want to help you, we want to educate you, we want to empower you and have you recognize that you're not alone in this journey with multiple myeloma.
 

(30:41):
So, I think for time's sake, I'm going to have to sign off, because we try to keep these to half an hour, so that they're reasonable with everyone's busy schedule. Thank you again, everyone for joining us. I wish you the very best. And, we look forward to interacting with you very soon. Don't forget to go to myeloma.org for all the resources that you need. Thanks again.