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ASH 2020 Multiple Myeloma Daily Wrap-Up: New Treatments & Hope

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Published on December 8, 2020

Experts Discuss Promising Treatment Options for Multiple Myeloma Patients

Multiple Myeloma experts Dr. Noopur Raje, Dr. Faith Davies, and Dr. Gareth Morgan discuss promising new treatment options being presented at the 2020 American Society of Hematology (ASH) Annual Meeting & Exposition with Patient Power co-founders Andrew and Esther Schorr. The panel also shares thoughts on the latest in testing, how quickly advances are being made for patients, and whether you should get the COVID-19 vaccine when it becomes available.

This program is sponsored by GlaxoSmithKline. This organization has no editorial control. It is produced by Patient Power, and Patient Power is solely responsible for program content.


Transcript | ASH 2020 Multiple Myeloma Daily Wrap-Up: New Treatments & Hope

Andrew Schorr: Hello and welcome. I'm Andrew Schorr from Patient Power. And you are?

Esther Schorr: Esther Schorr from Patient Power.

Andrew Schorr: And we're so excited you could join us for this live wrap-up, as the American Society of Hematology meeting is going on virtually this year but still with a lot of power and a lot of news about multiple myeloma. Thank you so much for joining us. We're in Southern California, but we want to connect you with our experts who are elsewhere in the country but are very involved in multiple myeloma for their whole careers and of course, in the ASH meeting in research. I want to thank our sponsor for sponsoring this, and that is GlaxoSmithKline. And I really appreciate that, although they have no editorial control. So we're going to talk about what we're going to talk about and we want your questions, right?

Esther Schorr: That's right. So if you have a question during the course of the program, take a look at the bottom of your screen there's a Q and A button and feel free to put your question in there. And actually, I'm looking at the questions that come in, our producer is looking at them and I'll kind of elbow Andrew during the course of the program and see which questions we can get answered in the course of conversation with our experts.

Andrew Schorr: Okay. Let's meet our experts. So joining us from Boston and Massachusetts General Cancer Center is a dear friend, Dr. Noopur Raje. Noopur, thank you so much for joining us today and being with us on this program once again.

Dr. Raje: Thank you for having me, Andrew. It's a real pleasure to be here today. Thanks for having me, Esther.

Esther Schorr: Good to see you.

Andrew Schorr: Okay. And we have another couple joining us. And they're sort of a dynamic duo in multiple myeloma, Dr. Gareth Morgan and Dr. Faith Davies. They're joining us from New York City. Thank you two. Gareth, thank you for joining us once again.

Dr. Morgan: No, it's a great pleasure to be here. It's always great to see old friends and you are like old friends now.

Esther Schorr: Same.

Andrew Schorr: Okay. Faith, thank you for joining us too.

Dr. Davies: Lovely to see you both and thank you for having me.

Andrew Schorr: Okay. Let's get everybody's title because I want the audience to understand these are true multiple myeloma experts, researchers and treating patients. Noopur, what's your title at Mass General?

Dr. Raje: So I direct the Myeloma Program at Mass General, Andrew. And I'm also a Professor of Medicine at Harvard medical school.

Andrew Schorr: Okay. Gareth, how about you?

Dr. Morgan: I'm Professor of Medicine and Director of the Myeloma Research Program at NYU.

Andrew Schorr: At NYU. And Faith.

Dr. Davies: So, I'm a Professor of Medicine at NYU as well. And I'm Director of the Clinical Myeloma Program at the Perlmutter Cancer Center.

Andrew Schorr: Okay. Well, thank you.

Esther Schorr: Seems like the right people to be talking to.

What Should Patients Know About Multiple Myeloma and COVID-19?

Andrew Schorr: That's for sure. Okay. So, let's start with what's on everybody's mind, and there's a personal experience here, and that is, Dr. Raje the last time we talked to you, you were actually at home because you were recovering from COVID and your husband who's also a physician had been hospitalized and was quite seriously ill. So here we are on the eve maybe of vaccines that will start to roll out, we hope, would you want to make a comment about COVID as it relates to the myeloma population and what you're telling your patients?

Dr. Raje: Sure. Absolutely, Andrew. COVID's not gone away as you know, we still have COVID. And in fact, we are seeing a massive surge, we still haven't sort of appreciated post-Thanksgiving what the numbers are going to look like with COVID. I can tell you at my institution, we're already preparing for a surge. The numbers in Massachusetts are going up even higher than what we saw in the spring.

So, the good news is, there is a vaccine coming down the pike but remember the vaccine is going to take a little bit of time for it to be available to all folks. I think the recommendation is going to be, the healthcare providers are going to get the vaccine first and then nursing home patients followed by immunocompromised patients. When it comes to that, that does include our myeloma patient population. And absolutely, when the vaccine is available, I would encourage everybody to take the vaccine.

Having said that, both of the vaccines that we have approved; the one from Pfizer the one potentially going to be approved, the one from Moderna, all require two doses. And it's going to take a little bit of time for that immunity. So until we are able to vaccinate folks, we still have to continue to isolate, continue to mask up and continue to be really very careful through this period of the holidays. But at least there's light at the end of the tunnel. And I think compared to where we were in March, we know a lot more. We have therapeutics as well, in addition to the vaccines, which is all good news.

Andrew Schorr: Okay. And one last thing is, how are you and your husband doing, by the way?

Dr. Raje: We're both great and doing fine and volunteering for the surge.

Andrew Schorr: So, then the question is about people with a compromised immune system and I'm living with leukemia, will we get the response?

Esther Schorr: Will you get the response – but also, patients have asked us, is there a concern as with some vaccines where it's a live vaccine, like a live virus? I understand that that's different from the vaccines that are being developed now for COVID. Maybe one of you can explain-

Andrew Schorr: Gareth, maybe you can talk about it. What is the vaccine and will myeloma patients respond?

Dr. Morgan: So the vaccine is a messenger RNA that's altered, so just a small piece of the signaling molecule from the virus it's encapsulated in a lipid nanoparticle. And the good thing about the virus is, it'll get B-cell responses and T-cell responses. And although myeloma patients have a slightly reduced response rate to the virus, I still think it's important that when offered that patients agree to have it. It's a big step forward. It won't totally give them total freedom from protective strategies but if by mistake they get exposed, their chances of having a bad outcome with it should be reduced. So I think it's really important to encourage uptake of this vaccine.

Andrew Schorr: So Faith, people wonder, should they keep moving ahead with their myeloma treatment during this time, whether it's infused therapy or oral therapy? And they wonder, does it affect their immune system? What are you telling your patients during this testy time?

Dr. Davies: What we're telling our patients is slightly different now than it was when we first started having the virus around. Actually, now we're really stressing the importance of continuing your myeloma care. The hospital systems have adapted a lot, so we're doing a lot more via teleconferences and remote visits and so on. But I think it's important to get that balance between the risk of maybe exposure to the virus, but also the risks of myeloma itself and neglecting to look after yourself. So I think it's a discussion every patient needs with their doctor to make sure that that balance is correct. But usually at the moment, the balance is moving more towards, if you need treatment, to have the treatment. And as I say, we're learning about adapting it. So maybe trying to decrease the number of visits or maybe using tablets rather than infusions and so on and so forth.

Andrew Schorr: Okay, but get your myeloma care, that's your biggest threat, is get that. Okay.

What Multiple Myeloma News Is Coming from ASH 2020?

Esther Schorr: So let's move forward, because I'm sure that there's going to be a lot more discussion and discovery related to the virus and how it gets treated. But could each of you talk a bit about what the big headline is for myeloma patients coming out of ASH this year?

Andrew Schorr: Or more than one headline.

Esther Schorr: Yeah, there may be more than one-

Andrew Schorr: Noopur, you want to start?

Dr. Raje: Sure. Happy to start. So this is a very different ASH, we're all catching up on ASH from our homes. And I thought, actually, this was a better way of catching up with all the data because one could really see the data presented, we could be a part of the discussions as well. And the big story, even at this year's ASH, is looking at the BCMA as a target in myeloma. And there are different ways of targeting BCMA.

At last year's ASH, you heard a lot about CAR T-cells. This year's ASH again, there's a lot more about CAR T-cells. But what I found really exciting about yesterday's presentations was the use of off-the-shelf CARs, so allogeneic CAR T-cells, wherein you do not have to necessarily wait to collect cells and then manufacture them. And there is no time lag between actually giving patients back this.

The good news with an allo CAR T-cell against BCMA was, it was pretty safe. The toxicity was not that high in terms of CRS or neurotoxicity and at least as of right now, we haven't seen anything like graft versus host disease. So that to me, was really quite exciting. Obviously, the data is early and we've got to wait on it. But again, looking at off-the-shelf CAR T-cells is obviously exciting.

What Does BCMA Mean?

Andrew Schorr: Let me just interrupt for one second. Could you define BCMA and also CRS, those two acronyms you used?

Dr. Raje: Sure, absolutely. So BCMA stands for, B-cell maturation antigen. It's a protein which is pretty much expressed on all plasma cells and preferentially more so on multiple myeloma cells. So, all your myeloma cells will have BCMA, which therefore makes it a really very good target for these targeted immunotherapeutic approaches.

And the other thing which I mentioned was CRS, which stands for cytokine release syndrome. Now, this is toxicity which has been seen in the cellular therapy space. And it is largely because your T-cells go find your tumor, kill the tumor, and while doing so produce a whole bunch of proteins and can cause a cytokine storm because of all of these proteins released from the tumor cells and can make a patient quite sick. So certainly, we're seeing this with cellular therapy. But what you've also seen very excitingly at this year's ASH is bi-specific T-cell engagers which also have the same kind of toxicity of cytokine release syndrome and neurotoxicity.

What Is a Bi-Specific Engager?

Andrew Schorr: So Faith, what's a bi-specific engager, what is that?

Dr. Davies: So we know that we can have antibodies which are drugs that target a cell and usually, when they target a cell they just bind with one arm to the cell. What these bi-specific antibodies do is that one hand grabs hold of the myeloma cell, the other hand grabs hold of an immune cell; one of the patient's own immune cells, and it brings the myeloma cell and the immune cell together so that the immune cell can help to kill off the myeloma cell.

And as Noopur said, there's been lots of new drugs out there that have been described at this year's ASH. Not only ones that target what Noopur was talking about that BCMA, but also other molecules that are specifically on the myeloma cell surface. And so there were two other antibodies that were discussed there and they also seem to give very good response rates and had similar kinds of side effects, but also interestingly seem to work for patients that had maybe had the BCMA antibody or CAR T-cell before.

So, I think that essentially, we not only have CARs and we have the new antibodies that do handy antibodies, but we've now got at least three new targets that we can go for on the myeloma cells. So lots and lots of choices. Lots of data, and I think our heads are like spinning now as to how we take all of this data forward.

Esther Schorr: It sounds like you're trying to attack the myeloma cell from all different angles and it sort of depends on where it takes hold.

Andrew Schorr: And we use the targets in the immune system, working together to fight the myeloma. Okay. And we know that when you develop cancer, your immune system lets you down and the cancer cells proliferate. So how can we get the immune system to do its job and give it the strength to do that?

What Is the Role of Stem Cell Transplants in Multiple Myeloma Treatment Today?

Okay. So let's back up a little bit. Gareth, you have been doing this for a long time and part of the standard of care has been transplant for myeloma patients. So part of what's been discussed at ASH this year is, does transplant still have a role; either one transplant or even two? What's your view of where the data is coming out because many patients have been through it, others are saying, "Maybe I'll have to." Where do you think it lands now?

Dr. Morgan: So one of the key messages about treating myeloma in 2020 is, always use your best treatment in the upfront setting. Don't hold back and save your treatments for later relapse. And so the data from the session on the first day really examined the role of stem cell transplant in 2020. And despite some people really challenging the primacy of stem cell transplantation, all of the data suggests that if you're able to tolerate it, it remains the optimum treatment for patients with multiple myeloma.

And what Faith and Noopur described previously, I think is really exciting because basically we've set up a kind of a - you can think of it as a horse race of multiple different horses and riders with slightly different mechanisms of action, and they're racing to the finish line to give some new treatments for multiple myeloma. And the purpose, we're discussing it in the context of transplantation, is, what can we combine with transplantation or will these new drugs displace transplantation in the next five years?

Up until now, it's been an unreasonable expectation. But I think it's now a reasonable expectation, one that we can displace transplant as being the prime treatment for younger patients but also that we can increase the number of long-term survivors with myeloma getting above the 30% to 40% long-term survivor rate and really talk about cure for a subset of myeloma patients.

Esther Schorr: Wow. Wouldn't that be great. That would be great. Just before we move on, I'd like to encourage those of you who are listening to this conversation that, if you have any questions that occur to you, please ask them because it's very rare that we get all these wonderful minds working together all in one room virtually. So please let us know.

What New Treatments Are Available for Multiple Myeloma Patients?

Andrew Schorr: Well, all right, let's back up for a minute. So Noopur, we've had a number of treatments approved in the last year. So we have at least a couple of new monoclonal antibodies. We've had daratumumab (Darzalex) for a little bit. Well, we've been adding to that. They're not all the same and they attack differently. And then we also have, I think it's been within the last year, this other class of drug, selinexor (Xpovio) and learning how to use that. And you had told me a couple of years ago, you said we still have trouble with people with more advanced myeloma heavily pretreated, high-risk, et cetera. So, with all these new drugs, are we doing better for a wider swatch of myeloma patients?

Dr. Raje: I think so. For sure, Andrew, because if you think about... We'll talk about the monoclonal antibodies first. So daratumumab, obviously, was approved a little while back. Just last year we had the other CD38 monoclonal antibody approved, which is isatuximab (Sarclisa). At this year's ASH, just a few hours ago, we had Dr. Thanos Dimopoulos present data on the subcutaneous version of daratumumab in combination with pomalidomide (Pomalyst). And again, this combination has been extremely effective in the relapsed/refractory space specifically in patients who've had lenalidomide (Revlimid) and have been refractory to lenalidomide.

Again, at the same session, you saw Dr. Tom Martin present data on daratumumab in combination with the proteasome inhibitor. So, combining it with carfilzomib (Kyprolis), for example the IKEMA study, again showing pretty amazing response rates where we are seeing MRD negative disease in the relapsed/refractory space which in the old days we would never have imagined.

So, I do think all of these have really had a great impact on the outcome of our patients. These are off-the-shelf. These are not designer. They are in a clinic as we speak. And as we've gotten used to using them, we have a better sense of their tolerability. Specifically, the subcutaneous version of daratumumab is something which is really easy and extremely well tolerated.

I will mention another one which is, belantamab mafodotin (Blenrep). That has also been approved in the last several months. And in fact, it's really important because this is the first-in-class conjugate, a drug conjugate antibody, which has been approved against that same protein that I was mentioning; the BCMA protein, B-cell maturation antigen protein. So the first antibody drug conjugate approved in that space. And it's going to be really very, very helpful for patients.

And you mentioned selinexor, a very different class of drug. It's an oral drug. And a lot of data being presented at this year's ASH of selinexor in combination with daratumumab, in combination with carfilzomib, in combination with pomalidomide. And if you really dose adjust selinexor, it is something which is quite effective in patients with relapsed disease.

Can Drugs Typically Used for Other Cancers be Used for Treating Multiple Myeloma?

Andrew Schorr: Gareth, I wanted to you about two drugs that are approved for other conditions, other cancers, and whether they might apply, you're doing a lot of research. So one of them is venetoclax (Venclexta), which is approved in acute myeloid leukemia (AML) and also chronic lymphocytic leukemia (CLL) and then the other one is a drug I've taken for myelofibrosis (MF) called ruxolitinib (Jakafi). And I know Dr. Berenson was talking about that. So any thought about drugs for other cancers that might play a role in myeloma?

Dr. Morgan: So, I'm really excited about the role of venetoclax in multiple myeloma. They kind of did some randomized studies which showed that it was beneficial, but beneficial if you carried a specific molecular marker, the 11;14 translocation. And so patients that have that abnormality have a very high chance of responding to this agent which I think is very exciting because even people with heavily treated, notably relapsed disease, will respond to the single agent and those responses are enhanced by combining with the proteasome inhibitors. So I think it's a great new class of drugs.

And then what we're holding out for is for - venetoclax is a BCL-2 inhibitor. There are drugs called MCL-1 inhibitors. And those MCL-1 inhibitors, have huge promise in myeloma if we can give them to patients safely. But they're especially interesting for the 40% of patients that have 1q gain in amplification because the transcriptome unit that's overexpressed in those cases, makes the cells exquisitely sensitive to MCL-1 inhibition. And so we'll then start to have two subsets of myeloma where you can target specific therapies, which is a kind of breakthrough for the area because we're heading for personalized therapy instead of a one-size-fits-all. And if we can make that transition, I think we can continue to make these exciting or the exciting progress will continue that we've made in the last decade.

Esther Schorr: So one of our listeners asked about another drug that I haven't heard mentioned yet, maybe it's been mentioned by another name, belamaf that was approved in July of this year. Did you mention that?

Dr. Morgan: Go back to Noopur, I think that's what she was describing.

Esther Schorr: Okay. Somebody is really asking about that.

Andrew Schorr: That was the other monoclonal antibody, so we're discussing it.

Esther Schorr: Okay. Sorry.

Andrew Schorr: But that brings up the whole question. So you have monoclonal antibodies, you have selinexor, you have venetoclax that has promise for people with a certain subtype, maybe some other drugs, these other - did you say MCL?

Dr. Morgan: MCL-1.

Andrew Schorr: Right, MCL-1. So Faith, how does a myeloma patient and their doctor know what's right for them?

Dr. Davies: Okay. So I think there's a couple of things in that. The first one would be to make sure that when you see your doctor if your myeloma does come back, that you know a little bit about the genetics of the myeloma cells and there's lots of FDA approved tests now to help us know a little bit about that because that gives us some more information about which drugs may be best. So as Gareth was saying, there's one group of patients that may respond to venetoclax well and that's a test that you have to do on the myeloma cell itself. So when you're discussing with your doctor, decide whether you need to have a bone marrow test done or not.

The next thing is really, we've got lots of choices and that's hard for doctors and patients but also good for doctors and patients, because that means to some extent, we can begin to match patients to the right treatment. So we can maybe say, "Right. Okay. This patient did really well with drug X, then we should maybe think about using drug X again," or, "Hey, this patient did not do well with drug Y, let's stick away from drugs that are either drug Y or drugs that look exactly like drug Y." Also, it means that we can think about side effects. Let's say a patient particularly has problems with neuropathy, there may be some drugs we want to avoid whereas maybe if they have problems with their heart, there may maybe other drugs we want to avoid.

So, although it's complicated and we have lots of choices, it's actually a great thing for patients. And I think it also highlights a little bit about making sure you have a good relationship with your doctor so you can discuss these things. And maybe as well, if your doctor is a more general oncologist, which is great, maybe ask your doctor if it would be worthwhile seeing a specialist myeloma doctor; not all the time, just maybe once a year or something like that just to catch up and make sure that things are going according to plan.

What Does MRD-Negative Mean for Multiple Myeloma Treatment?

Andrew Schorr: I can't underscore that enough. And now, you probably are doing more video visits and maybe data is being sent to you and you're talking to Mrs. Rodriguez or Mr. Smith at a distance who's in a remote area as a community oncologist but weighing in on their care. And I'm sure you as myeloma specialists are doing that. Noopur, I want to ask you about a kind of test we haven't mentioned yet and that's MRD testing, either minimal residual disease or measurable residual disease. Where does that come in, in myeloma? What's your thought about it?

Dr. Raje: Right. So MRD, as you've mentioned Andrew, is something which we are incorporating in clinical trials all the time now. As I've already mentioned, we've actually started seeing MRD negative disease even in the relapsed space, underscoring the fact that the medications we have now are so potent that we can get to a molecular level of not being able to detect disease. So the goal going forward should be to try and achieve MRD negative status. We've already shown in multiple settings that if you can get to that MRD negative status, you're going to do much better. And therefore, we've incorporated it pretty much in all clinical trials as we speak.

The kinds of tests you use, the different tests and at this meeting also we've discussed them. You can have a molecular genetic test, which is done more commonly in the United States. There's another flow-based test. And more recently what we've started doing is, blood tests which can look at the protein level at a molecular level and that's been exceedingly helpful in trying to determine MRD testing.

Should MRD testing be done in all patients in clinical practice? I would say that we are doing it more and more often, but more specifically in patients who have high-risk disease. I certainly think we should aim for that MRD negative disease state and really incorporate that into clinical practice in general.

Andrew Schorr: Just one question, maybe for you, Gareth. So if somebody is MRD negative, can you take a break from treatment?

Dr. Morgan: I would seriously caution against that. So some data here from the FORTE study and data from the ixazomib (Ninlaro) maintenance study said that even if you're MRD negative, if you stay on maintenance and you continue to expose the cells to toxicity that you'll do better long-term. And so not all response is the same, not all MRD negative states are the same, and that being undertreated is as bad as being over-treated. So we have to work out how to use this information to use treatment properly and we don't know exactly what to do at this point in time. But this meeting showed some new insights which I think will help the way we use the technology in the clinic.

What Is the Significance of Timing for Stem Cell Transplants?

Esther Schorr: So I want to follow up with something we were talking about earlier, Gareth. That one of our very astute listeners was reacting to your comment about transplant earlier, and wanted to know how you reconcile that with the IMF 2009 presentation about overall survival rates. And if you're doing an upfront transplant, is there much of a difference between doing it early and doing it late?

Dr. Morgan: So, I think that's been the question that people have raised for some time. So there was an early study that said, if you did transplant upfront or waited until relapse that there was no difference in overall survival. I think what's changed is that some data has come out in the last year that tells you about how many people get to first-line, after your first, the second-line treatment and to third-line treatment. And I think something like only 70% of people ever get their first-line or their second-line treatment, and only 40% get third-line treatment. So a lot of people never get exposed to what could be one of the best treatments. And so I think that's an important consideration for patients and for doctors.

Esther Schorr: Thank you.

Andrew Schorr: Okay. So again, if you have a question for our viewers, just hit that Q and A button, it goes to Esther and Rob our producer will get to as many as we can. Do you have another one?

How Do You Determine “High Risk” for Multiple Myeloma?

Esther Schorr: Well, yeah. There is a good one. Audrey who is listening has asked, "What is considered high risk?" How do you know if you're high risk?

Andrew Schorr: So Noopur, you want to take that one?

Dr. Raje: Sure. So high risk the way we define it today is based on genetics. What's been accepted is, if you have certain translocations; so t(4;14), t(14;16) and the deletion 17 or the p53 mutation are considered high risk. I think more and more of us have started believing that if you have some chromosome 1q abnormalities, also that would portend a higher risk in terms of outcomes. This is where I think when Faith mentioned, when you look at your bone marrow and do the testing on your bone marrow, it's really important to look at the cytogenetics and the FISH data on the bone marrow which allows us to define whether you're high risk or not at the outset.

How Has COVID Affected Multiple Myeloma Treatment Practices?

Andrew Schorr: Faith, so we're doing this during the pandemic, and you have literally this sort of alphabet soup. We were just talking to Noopur about FISH data, so that's a kind of test. We talked about MRD and all this kind of stuff. So let's say Mr. Jones comes to you at NYU. The family's not allowed to come with him. So what are you doing now so that the whole family understands that patient's situation and you can all make a decision together, how are you doing that?

Dr. Davies: No, I completely agree. One of the things we're doing is like what we're doing now is, we're trying to... If the patient is not allowed to bring a family member with them or is unable to bring a family member with them, then trying to tune the family into the conversations is really important and even if there's just two of you actually. So either recording the conversation, so when you go home you can play it back or indeed FaceTiming somebody into the conversation or Zooming somebody into the conversation. All of those things are so important because it means that everybody hears the information firsthand and that everybody remembers something slightly different from the consultation. Even if you think you're going to remember everything, you don't. And that's not from a patient perspective, that's from a doctor's perspective as well. When you're on the other side of the fence, you never remember everything. So I think it's really important.

How Do You Know Who Needs Myeloma Treatment, and When?

Andrew Schorr: I want to skip back to the other end of myeloma, into smoldering myeloma and maybe even people who've been told they have MGUS. So Noopur, how do you know who needs treatment and when?

Dr. Raje: Great question, Andrew. We had a really good biology section and that really focused on trying to understand smoldering myeloma and trying to define who are the ones who will actually progress. So we have a new model system which we refer to as 20-2-20, that is based on bone marrow plasma cytosis. So if you have more than 20% plasma cells in your bone marrow, if you have more than two grams of protein and if your free light chain ratio is off by 20, you're at a slightly higher risk.

The data which was actually shown is despite all of these sort of risk stratifications that we have, we're really not good at identifying at least half the patients who would actually progress. And at this year's ASH, we had really nice data on the genetic signatures of the myeloma tumor cells which could portend a higher risk towards progression. So I think we're still learning, we don't know it all. And the best way of figuring it out is really following these patients very carefully.

So, if you have a monoclonal protein and you have been identified as somebody who has smoldering myeloma, I always say you have to look back and you have to follow a patient for a little bit of time, in addition to all of these testing modalities that we have, to figure out whether you're the one patient who is going to progress. There's a lot of research going on in this space and I would encourage all of you, if you are somebody with either MGUS or smoldering myeloma, to reach out to your myeloma specialists and figure out if there's something which is appropriate in terms of clinical trials in that space.

Andrew Schorr: Wow. Go ahead, please.

What Are the Most Important Questions New Myeloma Patients Should Ask?

Esther Schorr: I've got a question and I'm paying deference to someone in our audience who says they've just been diagnosed with multiple myeloma. And so really what their question is, is there's all this research going on, there are all these new treatments, but what are the key things that somebody who is initially diagnosed with multiple myeloma should be talking to their specialist about?

Andrew Schorr: Faith, do you want to take that one?

Dr. Davies: Okay. So I think the first thing is to make sure if you're a new patient, writing your issues and problems down before you get to your doctor is really important. So you've got like a list, so you've had a chance to think about it because you forget things when you're in there. And then also, try to think about what are the things that are bothering you the most, is it pain? Is it just the path forward? And so on.

And then the next kind of questions that you're going to discuss with your doctor is, what are your aims of treatment? Because everybody has slightly different thoughts about where they want to head with their treatment. It hangs a little bit on how fit you are and how old you are and what kind of side effects you're able to tolerate. And so I think, trying to think about what your aims of treatment are. Once you've come up with your treatment strategy, maybe make sure you know what the side effects are and what you can expect both in relation to the immediate side effects but also the kind of long-term side effects. So those are the initial things that I would be thinking about.

Esther Schorr: Thank you.

How Do You Manage the Side Effects of Multiple Myeloma Treatment?

Andrew Schorr: So Gareth, your partner just mentioned about side effect management and cancer drugs are powerful, transplant is a big deal. So what tools do you have now and what research is going on so that you can have sort of kinder, gentler treatment, a managed side effects now and in research have drugs that are less toxic?

Dr. Morgan: So there are some important things about the use of new drugs which have totally changed the landscape. So using combinations of three drugs was better than a combination of two drugs. So if you use a combination with four drugs, the depth of response is much better than it was previously. And you can design the four drug combinations now so they have very little toxicity. And people understand how to manage the drug so you don't get peripheral neuropathy.

So, I think we're getting very excellent, complete responses with four drug regimens that compare to what we used to get after a stem cell transplantation. And so that led or this led some people to think about dispensing with transplant altogether because we did hear some data in the meeting about a mutation spectrum being exposed to the transplant conditioning agent induces in the myeloma cells which could enhance progression and even predispose you to getting secondary leukemia.

So, there are some very cogent arguments about side effect profile and responses. What you want to achieve though, is the deepest response that you can. It doesn't matter if that's before a transplant, after a transplant or irrespective of transplant. And you should try and maintain those for, I think, one to two years because there was some great data that says, if you're negative over a prolonged period of time or sustained MRD negative, those are the patients that have the very best outcomes. And so again I’d say, we're starting to learn how to use this information and patients are really benefiting.

Andrew Schorr: So Noopur, is this refinement what's going on? I'll take an example. So there was this new class of medicine selinexor which people were complaining about, had side effects by itself. And I know there've been studies now to use it earlier in combination and maybe dosages have been changing as well and so it can be effective, but have fewer side effects. Is that the kind of refinement that's going on as well?

Dr. Raje: Sure. So, in certain drugs, specifically selinexor, I think we've learned how better to use it. Instead of using it the twice weekly way the way it was approved, we've now gone to once a week, we've dose reduced. And again, as Gareth has pointed out, when you start combining these with other effective drugs, Andrew, you are able to dose reduce all of them and by doing so you mitigate the side effects of all of these and yet get a deep and durable response which is the key to controlling your myeloma.

Andrew Schorr: Okay. Esther, other questions?

Is it Safe to Continue Myeloma Treatment During COVID?

Esther Schorr: Yeah. There is one question here that sort of stretches over a lot of things we've talked about. This is from somebody who is 71 years old with multiple myeloma and has been tested to qualify for a BMT before COVID. And two concerns, the hospital doesn't allow visitors and this person feels they need their spouse there as an advocate and wants to know whether it's an overreaction to not wanting to delay this. The other is that the hospital is ground zero for COVID-19 testing and patient handling, so is it really safe to get a BMT there under current conditions? So who wants to handle that one?

Andrew Schorr: Faith, do you want to try? I mean, we don't know the hospital.

Esther Schorr: South Florida.

Dr. Davies: Well, we don't know the hospital. What I would say is, we live in New York City and our hospital has previously, I guess, been ground zero for COVID. And I would actually now say it's probably the safest place to be because all of the staff are tested, the rooms are cleaned and the actual facilities and everything, we've all had six or nine months of realizing what we need to do to make sure our patients are safe; those that are positive and those that are negative. So working on the assumption that all hospitals are as good as the one I work in, I think the patient should be safe. So that would be number one.

Number two, I think, yes, it's difficult. And I think as far as delaying transplant is concerned, I think you need to talk to your doctor because every patient is a little bit different. And that was the conversation that Gareth was having earlier because you're correct, there are some studies that suggest that if you've had an amazing response to your initial treatment that actually you might be able to delay your transplant to later. Whereas there are other studies that say, maybe if your response to your initial treatment hasn't been so good that maybe delaying is the best thing.

If you are going to delay it, then there are other ways of kind of managing the interim period. And certainly, there's lots of kind of data for slightly older patients suggesting that having some maintenance therapy is actually a good idea. And some of those patients actually end up with the same kind of outcomes as the younger patients. So there are also different ways to do this. And so I think it's very much a patient specific thing and to have a good chat with the doctor about what are the benefits and risks and being able to judge them.

Esther Schorr: Thank you.

Andrew Schorr: I'm going to try to put this together in my head and let's see if I've got-

Esther Schorr: Good luck.

What Are the Key Takeaways for Multiple Myeloma from ASH 2020?

Andrew Schorr: Okay. I'm going to see if I'm a reporter here. Smoldering myeloma. Testing to see where you are, Noopur, as you were describing. What's your smoldering myeloma situation? Gareth, you were talking about hitting it hard early when your myeloma will be most responsive and that could be a four-drug combination. And then also with people who've been heavily pretreated, perhaps some of these immune therapies may come into play, CAR-T or variations on that. Nod your head if I got this right.

Dr. Morgan: So I'm going to contradict you a little there.

Andrew Schorr: Please, you're the professor.

Dr. Morgan: Always very difficult with the scores because there are two of you, but I've got Faith to back me up tonight.

Dr. Davies: That's not always guaranteed.

Dr. Morgan: Yeah, it's not going to help. I've lost it now. So these immune agents, like you said yourself Andrew, the immune system is damaged in late myeloma. So the fact that we see 70% to 80% response rates and some people who get complete responses in that setting are living out beyond two years, which was unthinkable when we first started. Pomalidomide was approved because of a two-month improvement in PFS in the same population. And now we've seen people that are alive and well with no evidence of disease two years beyond their treatment suggest that if you have a good immune system at presentation, you should expect even better results than that. So what the race is, is how to get that treatment to the frontline setting where patients’ immune systems are functional so as we can get the best outcomes for patients.

Andrew Schorr: So the CAR-T or variations on that, these others that harness your immune system, move that earlier.

Dr. Morgan: Absolutely.

Andrew Schorr: Okay.

Dr. Davies: And that's where the clinical trials are ongoing at the moment. So I think in either next year's ASH or the ASH a few years later that's what we'll be talking about rather than these treatments being effective for relapsed and refractory patients, we'll hopefully be saying how great they are for newly diagnosed patients.

Andrew Schorr: Okay.

Esther Schorr: Well, then the other thing is in all of this, it sounds like getting thorough testing upfront to know what the bad actors are is critical to be able to do this matching of genetic issues.

Andrew Schorr: Right. And one other point, and Noopur I know you'll underscore this is when you sit across the table or in the exam room with a knowledgeable myeloma doctor that clinical trials and your potential participation is part of the discussion, am I right?

Dr. Raje: Absolutely. In a way, I always say this Andrew, we are where we are because of the clinical trials we have and because our patients have been absolutely fantastic at partnering with us and really trusting us in doing the clinical trials. We've gotten a lot of approvals and our hope is that the CAR T-cells will get approved in the next month or two. So absolutely, clinical trials are critical.

Andrew Schorr: Right. And Gareth and Faith, right?

Dr. Morgan: Absolutely.

Andrew Schorr: All right. So I just want to get a final message of hope, right?

Esther Schorr: Yeah, absolutely. I just want to say, for those of you who we haven't gotten to your questions, we are saving them for the next time we can get some experts together to try to answer them for you.

Andrew Schorr: Right. And our hope is, as we go into, well, later in this year but even in certainly in to 2021, we'll be doing our Answers Now series that both Faith and Noopur were on recently, we'll be doing that regularly in multiple myeloma.

So how do you want to tie this together? So let's start with you Faith. So we have people where they were newly diagnosed; they have smoldering myeloma, they have more advanced or their loved one does. When you look at what you've heard from ASH and what you're involved in personally, how do you want to position it to what you know and maybe what they could feel?

Dr. Davies: So I think this is the first ASH I've ever been to where I've seen exciting data in all of those areas you've mentioned. Sometimes I've come away and there's been one take home message, whereas this year I've heard data in each of those areas that's really made me think, "Wow, we're making so much progress." So I think that I'm excited, I really am. And it's not just progress in, oh golly, 10 years’ time, it's as Noopur said, progress that we can see in the next couple of months. It really is making a big difference.

Andrew Schorr: Noopur, how about you? How do you want to leave it with our audience?

Dr. Raje: So very, very hopeful Andrew and Esther because we keep talking about myeloma being an incurable cancer, I'm going to argue and say that we are going to be curing more and more patients every year. As Gareth and Faith have pointed out, the power of immunotherapy is finally being harnessed in myeloma which is absolutely incredible and we are bringing it up upfront. So early instead of transplant, we're using CAR T-cells, we're using off-the-shelf CAR T-cells. And with all of these and the BiTEs, I do think we're going to have long and sustained remissions which is the first definition of cure. So I do think we are very, very close and we are at the threshold of curing this otherwise incurable disease.

Andrew Schorr: I feel like giving all of you a big hug.

Esther Schorr: I know virtual hugs.

Andrew Schorr: Yeah. So Gareth how about you, you get the last word?

Dr. Morgan: So I think I've seen a lot of changes in myeloma because I'm the oldest of the assembled experts. I'm kind of tremendously hopeful. I think we've cured small percentages of patients previously, but the percentage of people cured is going to really change. And it's not five years, it's not 10 years, the next two years will see the introduction of these agents upfront with the aim of cure. And I think the companies that are brave enough to engage in that question, are the ones that will be ultimately successful in this area.

Andrew Schorr: Wow. Well, thank you all for what you do and for being a partner with us on Patient Power as we do these programs continuing, and for your devotion to patients. Noopur, we're delighted that you are doing well. You recovered from COVID. Your husband did, who had a serious go. And all of you are so devoted to patients and we want to thank you.

Esther Schorr: We really appreciate it.

Andrew Schorr: We want to thank you all. Dr. Noopur Raje from Mass General. Dr. Gareth Morgan and Dr. Faith Davies both from NYU in New York City. Thanks for being with us. We'll let you go.

Esther Schorr: And I want to thank all of you who have hung in for this session, I hope you've learned a lot from today's discussion and there'll be more of them. Stay tuned on Patient Power. We'll have a transcript of this, as well as a video of what was discussed. And make sure that you share that with others who might find it interesting. If you haven't already subscribed to our e-newsletter, you can easily do that on our website. And what else am I forgetting?

Andrew Schorr: Well, only just that, as we play the little music at the end now, then a survey pops up. So don't disconnect because-

Esther Schorr: It takes two minutes.

Andrew Schorr: Do the survey. Tell us how we did. Tell us if you liked the doctors. What made a difference for you, because that's what helps us get funding to do programs for you all of next year. And please, stay safe. Get a vaccine when it's available. Be wise about the holidays. And let's have a healthier 2021, okay. All the best.

Esther Schorr: What else do we say?

Andrew Schorr: Knowledge can be the best medicine of all. We'll see you. Bye-bye.

Esther Schorr: Bye.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

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