Dr. Philippe Moreau, President of the International Myeloma Society, joins the HealthTree Podcast for Multiple Myeloma to share an update on the growing use of bispecific antibodies in myeloma care. Learn about how these therapies are being used, how the therapy is evolving, future development in the space, lingering questions researchers have that you can help answer and how to get involved in the HealthTree Real World Bispecific Antibody Study. 

Join the Bispecific Antibody Study

Jenny: Welcome to today's episode of the Health Tree Podcast for Multiple Myeloma, a show that connects patients with myeloma researchers. I'm your host, Jenny Ahlstrom.

Now, before we get started with today's show, I'd like to share how the HealthTree Foundation is the market leader in digital health advocacy. Next month is Myeloma Awareness Month, and we will be sharing some new and exciting technologies that will be announced on Myeloma Mondays. On each Monday in the month, we'll be doing a live stream to share new technologies that will help patients better navigate their care and contribute to myeloma research.

I can't wait to share these with you, so watch for our announcements and attend the live streams on Mondays in March. You'll quickly see how and why Health Tree Foundation is the market leader in digital health advocacy. We can move quickly to serve the needs of patients and researchers using our internally developed technology, and it's exciting.

And one more thing. Today we'll be talking about an important topic of bispecific antibodies and we'll be sharing a study we have opened for patients who have received a bispecific antibody. So please join the Health Tree Cure Hub Registry and join this study if you have received a bispecific antibody and everyone who has is welcome.

We will share more details during this show. 

Join the Bispecific Antibody Study

Now onto our show. Bispecific antibodies are a new class of therapy in multiple myeloma. There are currently three approved treatments in this space that we will discuss today with more on the way, even in 2025.

And it is essential that physicians treating myeloma patients are able to get up to speed as quickly as possible on how to best use this new drug class. We'll talk about ways the researchers can discover these insights using data from patients like you and me in the real world.

And with us today, we have Dr. Philippe Moreau - welcome to the program. Let me give an introduction for you just before we get started.

Philippe Moreau is head of the Hematology Department at the University Hospital of Nantes, France. He specializes in clinical hematology with a particular focus on multiple myeloma and its treatment with high dose therapy and novel agents. Dr. Moreau was appointed University Professor of Clinical Hematology at the Nantes Faculty of Medicine in 2003.

Professor Moreau was a member of the organizing committee for the 2011 International Myeloma Workshop in Paris. Dr. Moreau is currently a member of the administration council of the intergroup Francophone du Myeloma, and he was chairman of the IFM from 2006 through 2009.

He is a member of the steering committee of the International Myeloma Working Group. Professor Moreau was widely published with more than 250 peer-reviewed journal articles and reviews that have appeared in high-impact factor journals including New England Journal of Medicine, Journal of Clinical Oncology, Lancet Oncology, and Blood. He is a frequently invited speaker at the International Hematologic Oncology meetings and is a member of the editorial board of the Journal of Clinical Oncology, Blood, and Blood Cancer Journal. And very importantly, he is now president of the International Myeloma Society, which we're going to ask you to talk about. So let's get started.

Maybe you can start with just a brief explanation of what is a bispecific antibody and why are they so exciting?

Dr. Moreau: Thank you Jenny for this invitation and very happy to speak with you today, mostly about bispecific antibodies. So those antibodies are new immunotherapies, recently approved as you mentioned previously, and bispecific antibody is a drug that is able to target the myeloma cell, the tumor cells by binding to a specific antigen of this myeloma cells that is always expressed by the tumor cells and we have currently three drugs approved and they are targeting two different antigens the first one is BCMA for B-Cell Maturation Antigen.

This antigen this targets is always always expressed by the myeloma cell and the second one the second antigen that can be targeted is GPRC5D that is also always always expressed on the myeloma cells.

One arm of the antibody is targeting the tumor cell the antigen and the second arm of the antibody is targeting CD3 that is always expressed by T cells and the T cells are then redirected close to the myeloma cells within the bone marrow and they can induce the death of the myeloma cells by releasing very small molecules that can kill the myeloma cells.

So this is totally new way of treating patients and the first bispecific antibody was approved in 2022. So these are very recent drugs three of them are available. The first one is teclistamab targeting BCMA the second one is elranatamab targeting BCMA as well. We also have more recently a third by specific antibody that was recently approved by FDA but also by the European authorities EMA and the name is talquetamab and talquetamab is targeting GPRC5D.

Jenny: We came out with the monoclonal antibodies, I don't know, 2015 or so, 2014, I think daratumumab was approved. This seems to be a major advancement because it's binding to these two locations instead of one location. Do you just want to talk about the evolution of immunotherapy in general in myeloma? Because to me, this whole field has opened up and it's a completely different world.

Dr. Moreau: Yes, you're totally right Jenny. Daratumumab was the first monoclonal antibody approved for the treatment of patients with multiple myeloma targeting CD38 that is also always expressed on the myeloma cells.

But daratumumab has only one way of targeting the myeloma antigen the CD38 and is not specifically targeting the T cells so definitely we have now new immunotherapies the bispecific antibodies that are really increasing the efficacy to induce the apoptosis the death of the myeloma cells.

We have those bispecific antibodies and three of them are approved and they are used widely in the US, in Canada, all over Europe and now in many, many other countries.

But we also have some other type of immunotherapies that are the CAR T cells. So CAR-Ts that's much more complicated, let's we need to perform leukapheresis to harvest the T cells of the patients. And then subsequently those T cells ex vivo are sent to the pharmaceutical companies and two of them are promoting CAR-Ts.

Johnson and Celgene/BMS and it takes something like six weeks to manufacture to process those T cells and those T cells in the lab in the factories are produced to express to be able to express a specific binder to a myeloma antigen that is mostly BCMA.  so these are fresh viable cells that we are re-infusing after a specific manufacturing process of six weeks to target specifically the tumor cells. So that's one administration, one and done. And then the majority of the patients are going to respond. The response rate is ranging from 80 to 98%. And then th CAR Ts are expanding within the blood and within the bone marrow of the patients are killing the myeloma cells and then there is a long treatment free interval the patients are able to stay without relapsing during one two or three years so definitely that's something very very important because that's one and done.

For the bispecific antibodies we know - and we are using them by administrating those antibodies sub-q (as a shot under the skin) on a weekly schedule. So this is a treatment that is proposed until progression. So the patient has to come back and back again to the hospital at first weekly during six months and then every two weeks, but the administration is totally different.

The most important advantage of those bispecific antibodies is that they are off the shelf. They are immediately available and you don't need to wait for this manufacturing process that is associated with CAR T-cell therapy. You don't need to wait six, eight, 10 weeks before receiving the CAR T-cell You can receive them immediately.

So if you have a very active disease which is progressing very rapidly in fact you cannot wait for CAR T cell therapy and you can receive those by specific antibodies that are very active as well.

Jenny: So there's just different utility in all this new innovation that we're seeing in multiple myeloma in terms of immunotherapy.

Can we talk a little bit about the targets? Because you talked about BCMA, you talked about GPRC5D, but those targets are only on the myeloma cells. Were those discovered a long time ago? Because really before, I don't know, five years ago, you really hadn't heard about them that much.

And I know there's another one for cevostamab (targeting FCRH5) I kind of had it right.

Do you want to just talk about the targets, why they're so important, why there's little off-target functionality or things like that?

Dr. Moreau: So definitely that's something fascinating in BCMA for B cell maturation antigen was discovered more than 30 years ago, exactly in 1992 by a French group in Paris.

And immediately they saw that BCMA was expressed only on plasma cells without any expression on other tissues - no expression on the heart on the liver on the lung and the kidney

When you are proposing this treatment probably you are not going to induce any severe toxicity on other tissues because there is no expression and BCMA is a molecule an antigen that is essential for the survival of the plasma cells.

When you are using a drug that is targeting BCMA, you are killing the tumor cells, but you are also killing the normal plasma cells that are usually secreting our normal immunoglobulins. So you are inducing in fact a very severe immunodepression and you are increasing immediately the risk of infection that is the most important adverse event with BCMA by specific antibody.

So BCMA is now very well known in fact, we know that it is always expressed on the myeloma cells, on the tumor cells, but it took 30 years to develop agents targeting BCMA, CAR-Ts, because the two CAR-Ts that are currently available (ide-cel/Abecma and cilta-cel/Carvykti) are both in fact targeting BCMA, but also the two bispecific antibodies, teclistamab and elranatamab. So we’ve come really a long way between the discovery of BCMA and the routine use now of those very important new agents.

And for GPRC5D this antigen was discovered more recently. We don't know exactly what is the function of GPRC5D. What is its role in fact physiologically?

But we know that it is always expressed on the myeloma cells and that's very important but there is also an expression of this antigen this very small molecule GPRC5D on other tissues such as the skin on the nails as well and on the central region of the tongue.

That will explain the specific toxicity of talquetamab, this new agent bispecific antibody targeting GPRC5D because after the administration of this antibody you can experience some skin rash, you can experience also some toxicity on your nails but also a specific dysgeusia,  sort of oral mucositis that can really damage you know the way you are going to eat and weight loss is often associated in fact with this treatment so that's very important

Jenny: Because you can't taste anything,

Dr. Moreau: Yes, with modification of the taste as well. So that's very important to understand and to know and to exactly, well, try to have this correlation between the expression and the toxicity.

Jenny: So you mentioned the three that are FDA approved and there are some upcoming and some that even might get approved this year. Do you want to talk about those?

Dr. Moreau: Yes, in fact we have other bispecific antibodies currently in development and the majority of them are targeting BCMA.

We have for example, linvoseltamab, we have different companies, know, AbbVie, Regeneron and others that are proposing and developing this treatment with some minor modification of the target, the epitope with also some administration.

Some of them can be proposed with a single monthly IV infusion instead of weekly sub-q so the administration will also induce some new visits to the hospital or less visits in fact if you have a monthly administration only.

There is also another one the name is cevostamab that is developed by Roche and cevostamab is targeting FCRH5 and we already have some data of the combinations of different bispecific antibodies because if you have different targets you can think immediately in order to increase the efficacy the response rate and mostly the duration of the response to decrease the resistance to those bispecific antibodies why not combine two antibodies targeting two different antigens to increase the efficacy?

And we already have some data very recently published showing incredible results combining teclistamab and talquetamab for example.

We know also that cevostamab can be probably easily combined with other bispecific antibodies.

So this is the area of development of those bispecific antibodies, combinations, but also trying to use them at earlier lines of treatment. Because currently we are using teclistamab, elranatamab and talquetamab only in patients that are very, very advanced patients that are becoming refractory to the conventional agents and mostly patients that are triple class refractory.

Triple class refractory means refractory to proteasome inhibitors, (bortezomib and carfilzomig), refractory to IMiDs (that's lenalidomide, pomalidomide) and refractory to CD38 antibodies (daratumumab and isatuximab.)

Those agents are so active in refractory patients that obviously we would like to use them earlier, but we need to have some good studies, reliable data to propose those data to the health authorities and probably in the near future we will use those by specific antibodies earlier for patients at the time of the first, second, third relapse, but also probably as part of frontline treatment. We are already enrolling in the US and in Europe patients into studies looking at frontline therapy with those very important new agents.

Jenny: And are you looking for frontline because you see a healthier immune system as the patient is getting diagnosed or just that the drug is much more effective?

So you talked about the response rates of CAR-T being in the 80-90% range. And I think these bispecific antibodies are in the 50-70% range. Maybe I'm off and they're higher, but not maybe as high as CAR-T, but they're durable.

So what's the reasoning about using it frontline?

Dr. Moreau: Currently all new agents, all new drugs are developed at first in very advanced patients. And if active, if effective, then we are moving at earlier lines. That was the logical development of bortezomib in the past and now bortezomib is the backbone of many combinations up front, the same for lenalidomide, the same for daratumumab and isatuximab.

We are now moving at earlier lines because if we have 60% or 70% of a response and that's exactly the response rate that can be achieved with talquetamab, elranatamab, teclistamab, you can expect to have a higher response rate at earlier lines because, and you are perfectly right, the immune system is much more active and the efficacy will be immediately increased.

And then because we still have patients that are progressing after the frontline treatment. So we need to improve on the results of frontline therapy and maybe try to replace all drugs by new agents that are more active or to combine in fact those new agents with for example, lenalidomide.

We have some studies looking at lenalidomide maintenance versus maintenance with lenalidomide plus teclistamab or lenalidomide plus elranatamab.

We know that it's feasible to combine those new agents with let's say more conventional therapies. So the goal is to increase the efficacy definitely.

I believe that for example with frontline treatment currently in newly diagnosed patients transplant eligible we are already curing some patients, a significant portion fraction, but we need to increase this cure rate and probably new immunotherapies will be more than helpful in this setting.

Jenny: I want to ask a follow up question before we move on because I'll forget. You talked about IV versus sub-q administration and different types.

Have you seen a difference in the impact or the efficacy of the drug when given a bispecific when given IV versus sub-Q?

Dr. Moreau: Well, in fact, when you are looking at the data that are available and we now have not only the results of pivotal studies for the approval of teclistamab and elranatamab, for example, but we also have now a lot of published data in the real world setting. The response rate is roughly identical, always 60 to 70%.

IV is not increasing the response rate. It seems that the efficacy of those new bispecifics in development monthly IV is not increased.

I don't know if it will be more convenient for the patients. Are they going to prefer sub-Q every two weeks or monthly IV? We will see, but definitely currently from what we know, there is no difference for efficacy.

Jenny: Great to know. So with all this coming out, how do you as a clinician decide between the bispecific antibodies, especially when some have the same target. I know they're not designed identically (you were saying different epitopes and things like that). But how do you look at that as a clinician?

Dr. Moreau: Yes that's a very very good question, Jenny for sure.

BCMA bispecific antibodies, we have two of them available. Teclistamab was the first approved and a few months later, elranatamab was approved as well. In terms of efficacy, well, very, very similar results. So in some countries, only one is approved, teclistamab, because elranatamab came secondly, so everybody is using teclistamab.

In some countries, we have access to both and to be honest there is no big difference so you can select and you know for example in Europe we are looking very very carefully at the cost of those agents and if the cost is less for one or the other we are selecting one or the other especially with this very important factor.

The administration is identical weekly, sub-q and then every two weeks. And then when the patients are really in very, very good response, you can switch probably to the monthly administration. So what we are expecting is that with a sort of competition with the two companies that are producing the two BCMA bispecific antibodies, the cost will be decreased in fact. So this is something that is important as well.

Jenny: Well, when you think about treatment of multiple myeloma, to me, it seems like using your best tools in the toolbox at the very beginning of your therapy is going to reduce cost over the lifetime of the patient just because you're going to have less therapy, you're going to have longer remissions, and you're not constantly in relapse mode. And patients want that too. So I think everyone is aligned.

Dr. Moreau: Yes of course, but we have to be careful and to try to define, especially in the frontline setting, schedule of administration with a fixed duration of treatment. Because currently, my specific antibodies are used in the relapse setting until progression. So for a patient frontline, what is very, very important and I fully agree with you is to have a fixed duration of treatment and not treatment until progression. So we have to work on this and currently in some ongoing studies we are proposing two years of bispecific antibodies and not more than this in fact.

Jenny: Good point.  All right, well, let's talk a little bit about the side effect management because you mentioned it -  infections. And I'm curious now, were you talking about antibody combination therapies together as well?

How do you best manage the infection issue, the taste issue, the skin and nail issues? How are you looking at that? Do you see the cytokine release? Do you see any of the neurotoxicities with some of these therapies that are similar to CAR-T and how are you managing all of those things?

Dr. Moreau: When we are starting to administer bispecific antibodies such as teclistamab, elranatamab, we are starting during the first week with what we are calling step-up doses.

We are starting with a very low dose and two or three days later, a second dose with a dose of this bi-specific antibody and at the end of the first week a third full dose of the antibody. The goal of this step-up dose is to reduce the risk of cytokine release syndrome. Because we are killing immediately a very high number of tumor cells and doing that we can produce this very large cytokine release syndrome that can be dangerous for patients.

In fact, with this step-up dose, 70% of the patients are experiencing CRS, but only grade 1 or 2. And grade 1-2 means that easily manageable, in fact, in your hospital. Grade three, you need to go to the intensive care unit. And in fact, with this step-up dose, you are never experiencing grade three. So no stay initially and if there is a grade 1 or grade 2 CRS we can easily control this CRS with the administration of a drug that is an anti IL-6 antibody and the name is tocilizumab and toci is available in all centers.

In fact you can very easily control the CRS so the risk of CRS is reduced as compared with cell therapy because we know that with CAR T's there is always a 5-10% maximum risk of a grade 3 CRS of severe CRS and this is not the case for bispecific antibodies.

So when targeting BCMA with teclistamab and elranatamab as I mentioned previously, you are also killing the normal plasma cells.

So immediately you are inducing a severe hypogammaglobulinemia. That can be very easily checked with the dosage of normal immunoglobulins.

And at the end of the first month of therapy for all patients, you have a very low rate of normal immunoglobulins, IgG, less than four grams per liter.

If you are not proposing any IVIG supplementation that can be done very easily on a monthly schedule, the risk of infection will be very important and the grade 3 or 4 rate of infection is roughly 80% in fact.

It means that at the end of the day, all patients, almost all patients since the treatment is proposed until progression, will experience severe infection. And not only during the first month of therapy, but that can occur after 9 months, 12 months, 1 year and a half.

We first have to inform the patients about this risk and in case of fever they don't have to go to their GP (general practitioner), they need to see their hematologist. This is a very, very important message.

Now we have some guidelines, some international recommendations, proposing IVIG systematically at the end of the first month of treatment.

Jenny: Fantastic.

Dr. Moreau: If you are using IVIG the risk of infection is reduced dramatically and less to 20% probably, so this will add probably to the cost for sure because IVIG that's costing something.

We can also propose some systematic prophylaxis you know in some centers they are using levofloxacin for example, not systematically, but that can be proposed.

We are using also systematically cotrimoxazole to reduce the risk of PCP (Pneumocystis jirovecii, a yeast-based fungus).

We are also systematically giving valacyclovir to reduce the risk of herpes zoster virus infection.

Jenny: That’s great. Just knowing ahead of time that you can work in IVIG as part of the treatment protocol, I think is a really important idea.

Dr. Moreau: Yes, exactly.

Jenny: You talked a little bit about moving bispecific antibodies up to the beginning of treatment. In today's care, how do you see that being used strategically? When do you use it? For whom do you use it? Do you use it in combination and how is it best sequenced?

Dr. Moreau: This is a very very important question, we could spend hours speaking about this but let's try.

Jenny: It’s a tricky question.

Dr. Moreau: For example in elderly patients, patients that are not eligible for autologous stem cell transplantation, one of the standard of care currently all over the world is the combination of lenalidomide, dexamethasone and daratumumab, what we are calling DRd. That's widely used in Europe, in the US as well, in Canada, et cetera.

We can try to improve on the results of this combination DRd that is already a very, very good combo you know with a Progression Free Survival of more than five years and Overall Survival median that is also more than seven eight years, so definitely we can try to improve on these results.

There are some ongoing trials that are prospectively comparing DRd versus lenalidomide daratumumab plus teclistamab or lenalidomide daratumumab plus elranatamab so we are trying to replace dexamethasone with a bi-specific antibody.

Jenny: Great. Everyone hates dexamethasone.

Dr. Moreau: Definitely. We all strongly believing that those trials will improve the response rate, duration of response, overall survival as well.

That's one example. We can also use those bispecific antibodies after autologous stem cell transplantation to try to improve the maintenance part of the strategy. Currently, lenalidomide is the standard of care approved until progression but probably we are going to improve on the results of Len maintenance with bispecific antibodies.

We are trying as well to use them with a fixed duration instead a treatment of until progression.

Jenny: I have a question about the utility of bispecific antibodies in community clinics. You're doing step-up dosing. You're dosing patients in the hospital. You're watching them very carefully. Do you have a handoff that you do into community centers? Do you just have everybody come to an academic center? Because we want everybody to be able to take advantage of this newer therapy. How do you address that?

Dr. Moreau: That's a very important point and Jenny as you know CAR T-cell therapy is mostly used in university hospitals large academic centers and you need to have an intensive care unit etc, etc. For example in my country in France we have only 20 centers in the whole country that can propose CAR T-cell therapy.

Jenny: That’s still a lot.

Dr. Moreau: On the opposite end, for bispecific antibodies, all community hospitals can use them. You don't need to work in a university hospital because we don't have any grade three CRS. And currently, for example, in my country, you have more than 90 centers that are using in routine, teclistamab and elranatamab.

So this is feasible in community hospital very easily. If we want to be on the very safe side, patients can stay in the hospital during the first week, during the step-up dosing in order to control very easily grade 1 or grade 2 CRS.

But there are some programs looking at bispecifics in the outpatient setting. So the patient will receive the two, three first doses out in the hospital, but can come back home after each dose. So this is in development.

What is also proposed in some centers is to use prophylactic tocilizumab systematically infused before the bispecific antibody in order to reduce the risk of CRS and the risk of CRS is immediately decreased from 60% to 70% to less than 20% and we have some data published already on that.

Since the number of patients is really increasing with specific antibodies and that's not only for multiple myeloma that's true also for another heme disease (that is non-Hodgkin's lymphoma) we will have in the clinics plenty of patients.

That's good to develop those outpatient strategies and probably the way we are going to use them in the future will be different and more and more patients will be treated outside the hospital with those treatments.

Jenny:  That would be ideal. I think it's amazing. Now you talked about patients who potentially have highly aggressive disease and how bispecific antibodies might be a great fit because you're giving them on an ongoing basis. You don't have to worry about personalizing them. They're off the shelf. You don't have to think about manufacturing.

Are they equally effective or even better for patients that have maybe standard risk myeloma or not as aggressive disease? Or are you seeing certain bispecifics or utility in certain genetic factors of patients? So do you see it not work for a certain genetic factor or yes work for a different genetic factor? I'm just curious about that.

Dr. Moreau: In fact another very good question Jenny. In fact that's true for all types of immunotherapies, true for CAR T cell therapy but also for bispecific antibodies.

There are some groups subgroups of patients that are benefiting less in fact for those from those new treatments especially patients with poor cytogenetics, patients with extramedullary disease (EMD) and that's why we are systematically for example using PET CT to look at extramedullary disease before starting the treatment. Also patients with (a risk status of International Staging System 3 - ISS3) with a high beta-2 micro globulin level above 5.5 mg/L and also patients who are pent refractory (they have become refractory to two IMiDs, two proteasome inhibitors and one CD38 antibody). 

We know that those patients will respond less and if you are combining two adverse factors such as or poor cytogenetics plus EMD, then the response rate will be very, very low.

So we can try to predict in some efficacy of those new treatments.

But for standard risk patients, in fact, the response rate is very good. And what is very important, and that's what I'm telling to my patients every day - if you are going to respond to a bispecific antibody and two-thirds of the patients are responding, that's quite good in fact.

If you are responding, we are going to know very quickly if you are responding yes or no to those treatments. Because the time to first response is something like one month. And the time best response is three months.

Jenny; That’s fast.

Dr. Moreau: You know very very quickly if the drug will be effective and in case of response what is more important is the median duration of response.

And the median duration of response for teclistamab, for elranatamab is something like at least two years.

So you can wait a patient in front of you and the patients and families are very well informed now that very often bispecific antibody could be sort of last line of treatment.

The patients are, well, let's say very importantly happy to hear that two years from now, they'll still be with us, you know, and with all the new developments, all the new drugs that we are trying to develop, maybe in two years, we will have something new for them.

The most important information to my opinion is this one. If you are going to respond, the median duration of response is above two years. That's a very, very important information for the patients and for the families.

Jenny: It’s fantastic. So it's a highly effective therapy. Do you do any testing on the immune system itself to identify T cell function or the health of the immune system that you've seen be a differentiator in terms of how patients respond or not?

Dr. Moreau: That's another good point, know, can we try to identify biomarkers that are going to predict the efficacy of such treatments.

That's true that we can look at T cell function very well. Let's say we need simple tests that we are not doing yet in routine care, but this is feasible in some centers that have a specific translational research programs, etc. This is not done in routine care.

Jenny: What further development is being done to leverage the use of bispecific antibodies? You talked about combination therapies, you talked about bringing it up in earlier lines. What other strategies are you seeing as a researcher?

Dr. Moreau: We discussed previously about combining those bispecific antibodies. We already have some data, interesting data in very advanced patients, trying to use them at earlier lines as well, eventually in combination with CD38 antibodies, in combinations with IMiDs, et cetera.

here is huge development (happening), but there are still ways to try to make progress.

We know that we have now in development trispecific antibodies.

Jenny: It's incredible.

Dr. Moreau: We have heard at the last ASH meeting and we are going to hear at the very important meetings at ASCO, EHA, and the meeting of the International Myeloma Society that we have now antibodies that are able to target two different antigens on the myeloma cells. So one drug will be able to target GPRC5D and BCMA - or a single drug will be able to target BCMA plus CD38.

We have now companies that are developing those trispecific antibodies and that can be a way of making huge progresses for patients as well.

Jenny: That's fantastic. Very exciting that that's happening. Now, you have a lot of questions still, and there are only a certain number of clinical trials that can be run. So what outstanding questions does the research community have about bispecific antibodies?

Dr. Moreau: In my opinion that's trying to develop combinations first and to try to find the optimal dose to have the best balance between efficacy and safety. Trying as well to use them at very early lines of treatment.

We know that the pharma companies are doing those studies, but we need also academic trials with the support of pharma companies because the cost of those agents are very important and definitely academic groups, cooperative groups, academic centers cannot pay for the drugs. So we need the support of the pharma company as always.

Trying to define fixed duration of treatment because treatment until progression, that's really too much.

And even if the patients are happy to have a median duration of response that is above two years, can you imagine the number of visits to the hospital? And that's really a lot.

Jenny: Yes, it's a lot.

Dr. Moreau: We need to develop in fact those fixed duration of therapy schedules.

Jenny: Health Tree is partnering with the International Myeloma Society on this bispecific antibody study. Do you want to talk about the questions that you have that can be answered in this type of study? You talked about the clinical trials, they're essential for getting drugs approved and developed and then honed in, like you're saying, with the investigative-led studies.

But then there are a whole host of other questions that patients could help answer through their real-world experience.

Dr. Moreau: Yes, Jenny, that's key and thank you for all the efforts that you are doing, for proposing the data, for proposing service to patients, etc. Trying to understand better because we need to know, in fact, on a very large number of patients, what are the data in the real world setting?

What, how, how many times in fact, and for how many patients there is a switch to an administration, for example, every two weeks instead of weekly how many physicians are daring to use the the treatment on a monthly basis? What is the infection rate in fact in the real life? How many patients are receiving IVIG in order to prevent infections? Can we stop the treatment? Can we have also have re-treatment with bispecific antibodies because we don't have this information?

If one patient for example has to stop because of a severe infection and we are not retreating the patient because it takes something like two to three months to recover from the infection.

Patients can continue to respond (to therapy) during a very long period of time without any treatment. At the time of the progression we don't know if the bispecific antibody will be effective again.

That kind of information is very, very important for us to try to improve on the management of our patients.

Jenny: Agreed. why don't you explain what the IMS is?

Dr. Moreau: Thank you Jenny for this question. IMS is the International Myeloma Society. It was created a long time ago. In fact, with physicians, all of them very involved in the treatment of multiple myeloma.

And we have different aims, goals, research, and we are funding research. We are funding new physicians, new scientists to work in labs of excellence, to learn new tests, et cetera. So research, that's a very, very important part. And for example, last year we have funded for more than two millions of dollars in grants for new scientists and physicians.

So that's really very important. We are also promoting education all over the world. We are organizing the largest important meeting on multiple myeloma, the International Myeloma Workshop. That is an annual meeting. Last year it was in Rio de Janeiro and this year it will be in Toronto in Canada.

Jenny: Fantastic.

Dr. Moreau: And next year it will be in Glasgow, in Europe and this is the largest meeting you know with more than 2000 physicians and scientists sharing the data etc bringing new data and never published.

From an education point of view we are also trying to propose smaller workshops in different continents and especially low and middle income countries. Last year we did a very large meeting for education in South America. Next month we will be in South Africa. In three months from now we will be in the North of Africa, in Morocco to promote education for all physicians and scientists.

We are doing webinars in fact on the East Coast, West Coast of the US. We are organizing also workshops such as the Immune Effector Cell Workshop meeting in Boston every year. And the most recent updates on bispecific antibodies and CAR T therapies are presented there. So education, that's really a big job for us.

Advocacy is very very important. We are trying to speak with the authorities, FDA and EMA especially, to try to understand how we can propose the drugs, new drugs faster for patients, new endpoints for clinical studies, what they are expecting from the myeloma community to develop new drugs for example.

We had at least least two meetings already with FDA, one with EMA and the next one in a couple of months.

For example, we were promoting in front of the authorities, minimal residual disease (MRD) as a endpoint for clinical studies. So these are all the activities of the society and we are a global society for all countries.

We need also to have a good collaboration with patient groups because we are doing all this for patients. We know that there are other organizations or societies that are more involved for patients such as your organization there is also Myeloma Patient Europe, for example.

Jenny: They are great.

Dr. Moreau: With you (our partnership) is to have real world data. We also want to have a  better understanding of the treatment all over the globe and you know that unfortunately in many countries, are not available, new drugs are not available. So we are also pushing, you know, for drug access.

Jenny: Thank you for the overview because I think not a lot of patients might understand what the organization is. I've been so impressed. think Boston was the first IMS meeting that I attended. It was incredible. To me, it's the best myeloma meeting that I've ever gone to on a repeated basis. The content is fantastic. The topics are amazing.

It's so fun to see all the myeloma people in a space, you know, as opposed to an ASH (American Society of Hematology) or other meetings where it's multiple hematology cancers. So it's amazing and you have a very heavy focus on immunotherapy.

Dr. Moreau: Yes.

Jenny: We invited you (IMS) to participate on this bispecific antibody study. Let me just explain it for a little bit.

Dr. Moreau: Yes, of course.

Jenny: It’s a series of patient surveys to understand a patient's experience. So what was your experience? Did you receive the bispecific outpatient? Did you do it inpatient? What was the handoff like if you did it not just in an academic center? Did you get infections? What was the caregiver burden? Things like that that we need to understand about the patient experience.

And then we're also inviting patients to connect their medical records through their electronic health record or their EHR system because we want to open that data up to the research community on an anonymous basis.

So you (and other researchers) can see who did get IVIG? What was the sequencing? What kind of genetic features do these patients have? And who's responding best? What did they have before? What did they get after?

We have about 12 investigators that are partnering with us on this study, including IMS investigators and we have several hundred patients now who are participating in the study.

I want to just stress the importance of a study like this because it is very expensive to run these clinical trials and sometimes although you need to know the dosing and you need to know earlier uses in clinical trials, not all patients can join clinical trials. They should always consider clinical trials. We've always advocated for that, particularly in this podcast, the use of clinical trials, because you should consider that as a patient at every step in your treatment journey.

But 100% of patients who have received any kind of myeloma therapy can participate in research like this. You don't have to go to an academic center to participate in this type of real world research. And sometimes patients are healthier when they join a clinical trial and then they're getting the therapy it in the real world. Are the side effects the same? Is the efficacy the same? You know, we need to answer all those questions too.

I don't know if you have any comments about the participation or need for this kind of research.

Dr. Moreau: No, I told you already that’s very, very important. You can generate very easily, in fact, a lot of very important information regarding toxicity, regarding sequencing before CAR-T, after CAR-T, etc. etc. For us, physicians, know, and the International Myeloma Society will be more than interested in working with you on the results and the interpretation of those data.

Jenny: Yes, because there are questions that you'll have with the data that we might not think of. So that’s the next step.

So we're inviting all of our listeners, if you have had a bispecific antibody, we invite you to join this study. If you know friends of yours who are myeloma patients, we invite them to join this study as well. And we invite you to do that because you are helping contribute to your own cure in a major sense by sharing this information.

Join the Bispecific Antibody Study

Dr. Moreau: Yes.

Jenny: And we can’t do this with the speed that you want to do this with (and that patients want to see in myeloma research) without these types of studies.

You talk about the FDA, but there are so many stakeholders and patients are some of the largest stakeholders. For example, we now have a way to add side effect data to, if a patient connects their medical records, it'll show them in their profile what they can see for their prior lines of therapy.

(With HealthTree technology) we are automating lines of therapy based on a particular protocol. Now that's very hard in myeloma to do because many times it's very subjective. We're doing this in partnership with researchers so that it's an authorized (research-based) way of separating treatment into lines of therapy.

(With that in place) then you can do research -  show me all patients with three prior lines of therapy that had this or that.

We are also inviting patients to share their side effects. So we'll ask at multiple time points for bispecific antibodies because your side effects in the first two weeks might be totally different than six months out or a year out. And we're asking patients to do that.

When I go to the clinic I may not mention all of my side effects to my doctor. I might have five different side effects and I might only talk to them (my clinic team) about one.

So this is a way that patients can share what actually happened with this experience and then you can see that data anonymously or de-identified and then you can start to see trends and patterns and develop new hypotheses.

We're excited about our partnership with you. We look forward to doing a similar thing for our upcoming CAR-T study and want the International Myeloma Society to have access to this type of data because you are brilliant researchers and we're thrilled that you're working on this.

Dr. Moreau: Thank you.

Jenny. Thank you for this collaboration. That's really key. Thank you so much.

Well, we are thrilled that you joined us today to talk about by specific antibodies. And it's such a growing field in the world of myeloma.

It just feels like there were so many companies that jumped into the space and have solutions.

I just want to thank you for the incredible research that you're doing. Thank you for the service that you're performing with the International Myeloma Society and your leadership there. It's extraordinary what you're doing. I'm just so impressed with the organization.

Dr. Moreau: Thank you.

Jenny: And I want to thank our listeners for listening to the Health Tree Podcast for Multiple Myeloma. We invite you to join us next time to learn more about what's happening in myeloma research and what it means for you.