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Is Myeloma Research Examining Sequencing of CAR T and Bispecifics?

April 4, 2024/in MM Newly Diagnosed, MM Programs, MM START HERE, MM START HERE Webinar, MM Treatments and Clinical Trials, MM Videos ND, MM Videos TC, Multiple Myeloma /by Kara Rayburn

Is Myeloma Research Examining Sequencing of CAR T and Bispecifics? from Patient Empowerment Network on Vimeo.

Is the sequencing of CAR T-cell therapy and bispecific antibodies being examined in myeloma studies? Expert Dr. Ola Landgren from University of Miami Sylvester Comprehensive Cancer Center discusses what’s known about sequencing of CAR T and bispecifics and what needs further study in clinical trials.

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Transcript:

Lisa Hatfield:

So with both CAR T and some of the bispecifics approved, obviously if a patient comes in and they need something right away, they’ll take whatever is first available. But all things being equal, if a patient says, well, I can, I have both CAR T accessible and bispecifics accessible. There are some patients out there, I’ve spoken with some who are wondering, is there a benefit to sequencing one before the other, or are there any trials looking into that?

Dr. Ola Landgren:

There are studies that have allowed patients to go on treatment with one of these modalities. For example, the bispecific antibodies with the prior exposure to a CAR T-cell therapy. There are also trials with CAR T-cell therapy that has allowed patients who have been exposed to prior antibodies, either bispecifics or the conjugated antibody drug conjugates, Belantamab mafodotin. So if you look at those studies and see how the numbers compare, if you are not exposed or you are exposed, I think the data is not entirely clear-cut.

There is no definitive study. Some data suggests that maybe it’s not that different, but then there are some studies that suggest that if you go to the antibody first that maybe that would lower the efficacy of the CAR T cell. So some people have for that reason said the CAR T cell should be done first. To make it even more complicated, there are some studies that have then taken time into the equation. So that means that you could have the patient treated with the antibodies for BCMA and CD3, and the antibody is given successfully for a long time, for many years. And eventually, unfortunately, the antibody may stop working.

Now, if you switch back to back to a CAR T-cell therapy without any other therapy in between, some studies indicate that that’s less likely to be beneficial. But if you instead do another target, say you did GPRC5D/CD3, or you did a completely different therapy with small molecules or you did carfilzomib (Kyprolis), or you did venetoclax (Venclexta), or IMiDs, or different types of combinations that are out there, been around for a long time, and you get good mileage out of those combinations.

Now, if that stops working, if you now go to this other therapy, you go back to the CAR T cell, that will suggest that the results are not that different. So I think that there are aspects that we don’t fully understand. I personally believe, based on what I’ve seen, based on what I know from treating thousands of patients with myeloma for almost 30 years I’ve been a doctor, I think time is probably very, very important. So if you go back to back from one therapy to the other, that’s less likely to be beneficial. If you go from one therapy, and it stops working and go to the other drug with the same target.

But I would say it’s not that different from how we think about IMiDs or proteasome inhibitors. If you were to go single drug with a proteasome inhibitor and you switch to single drug with another proteasome inhibitor, or the same thing with an IMiD, that’s less likely to work versus if you went to something else in between. So we just need to generate more data and learn. Lastly, I want to say that in my experience, from all I see in my clinic at the current time, I think the choice that patients make is based on personal preference and to some degree also the situation of the patient. I saw a patient yesterday, 50 years old, who came from another country and has relocated to us here in Miami and asked, what are the options?

And we talked about CAR T cells, we talked about bispecifics. And considering all the different factors that CAR T cell would imply that we had to give some other combination therapy for two or three cycles while we harvest the CAR T cells and manufacture the CAR T cells and then plan for the admission and give it, and also that the patient was not really very happy about the side effects in the hospital with CAR T cell. That patient shows the bispecific, but I’ve also seen other patients in the same situation saying, I’d rather do these different steps for two or three months, I stay in the hospital, and then I enjoy being off therapy.

Actually, I saw another patient just a few days ago, a gentleman in his upper 70s who we had the same conversation, and he had picked the CAR T cells. And I saw him with his wife and he has been off treatment for two years doing excellent. So different patients make different decisions. And I think that is just how the field is evolving. So I think we should be open to individual patient’s priorities and what they want, and we should just offer everything. And of course, we can guide if a patient wants us to give direction, but I think presenting it and let patients be part of the decision-making, that’s the future of how medicine should be practiced.

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What Myeloma Patient Monitoring Occurs After Induction Therapy?

April 4, 2024/in MM Newly Diagnosed, MM Programs, MM START HERE, MM START HERE Webinar, MM Treatments and Clinical Trials, MM Videos ND, MM Videos TC, Multiple Myeloma /by Kara Rayburn

What Myeloma Patient Monitoring Occurs After Induction Therapy? from Patient Empowerment Network on Vimeo.

What is involved in myeloma patient monitoring following induction therapy? Expert Dr. Ola Landgren from University of Miami Sylvester Comprehensive Cancer Center discusses some common treatment and monitoring scenarios that he carries out with his patients.

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Transcript:

Lisa Hatfield:

So I think we’re going to shift a little bit to managing and monitoring multiple myeloma. Once you’ve had a patient go through the induction therapy, what kind of monitoring do you complete for your myeloma patients and in particular those who have reached a certain level response and are maybe on maintenance or continuous therapy, what type of tests do you do and how often regarding labs, imaging, bone marrow biopsies?

Dr. Ola Landgren:

There are a lot of different ways, obviously, of practicing medicine. So every center has developed models that they feel very comfortable doing. So I like details. I like to know things. I like to check things. I’m not excessive in ordering invasive tests, but I like to know. Also, I like to make sure the patient not only has good long-term clinical outcomes, but also good quality of life. And to me, I try to minimize the intrusiveness of what we do. So, for example, if I give a combination therapy where there is an injection or infusion, say week one, week two, week three, and then there is a week off. I recognize that if you do labs during that week off, you will have a better yield and understanding of how these three different injections or infusions actually have moved the disease forward and suppressed the disease.

But in my mind, I think that week off is a very important week off for the patient. So I would rather do testing the third day of the treatment at the treatment unit. So if it’s week one, week two, week three, I would draw the myeloma labs that same day. And that would give the patient six more days off from injection, infusion that third week and the whole fourth week off. So I would give the patient 13 days off. Again, these are small things. These are things I’ve thought about a lot. I’ve practiced medicine for many years and I recognize that having time off like that, many patients travel, they go on vacation, they do different things. So I don’t want to just randomly put a blood test in the fourth week just because I want to check after week one, two, three, and then have the assessment.

I sort of underestimate the benefit of the therapy and then I start the next cycle, say back to back cycle two and cycle three and so forth. I would typically do blood tests once a month following these principles. I do baseline and I would do the last day of injection or infusion. For a newly diagnosed patient, you ask me, I would for baseline always do bone marrow biopsy and an aspirate. I would always do a PET-CT for every patient as my default.

Sometimes we end up doing MRI. So that could be other things that are happening, but that is what we do for the majority of our patients. After we have completed four to six cycles of treatment for patients that are candidates for consideration of transplant with chemotherapy with melphalan (Alkeran), we would usually do a biopsy after four to six cycles and we would use that to determine what’s the optimal mobilization protocol for stem cells. When we do that, we would run a MRD test.

We would run our in-house flow cytometry test that we developed when I used to work at Sloan Kettering and we have developed that here in Miami as well. We work closely with Sloan Kettering, and we have set up this assay in collaboration in the new 2.0 version. We will also send the aspirate for the clonoSEQ at Adaptive Biotech, which is the DNA-based sequencing for MRD. We would send the patient for collection of stem cells. When the patient is back, we will continue treating. So if you say we do it after four cycles, we would collect, if we do it after five or six, then we collect.

After that, we would typically resume therapy and for the majority of our patients, we actually give around eight cycles of therapy, and we have seen that you can deepen the response. You don’t increase the toxicity, but you deepen the response for the vast, vast majority of our patients. When we have used our best therapies, we have done it that way…

We have even published on this, over 70 percent of our patients are MRD-negative, and many of those patients, when they come to cycle eight, they ask, do I have to do the transplant? And that is a controversial topic. But I think there are two large randomized trials that have shown the same thing, that there is no survival benefit with transplant. But you can also say that there is, in those two trials, a progression free survival benefit, meaning that the disease would stay way longer with transplant. But many patients say, if I reach MRD-negative, both those two trials show that if you’re MRD-negative without transplant, or you’re MRD-negative with the transplant, PFS was actually the same.

And given that there is no survival, overall survival benefit, why would I subject myself to go to that? Why don’t I keep the cells in the freezer and go right to maintenance? And we will have a conversation with every patient, they would meet our transplant team, they would meet our myeloma expert team.

And the individual patient will make decisions. I think over time, more and more patients have chosen to keep the cells in the freezer. For patients that are MRD-positive, we would counsel towards transplant, but there are patients that don’t want to do that, and we are not forcing any patients to do that. We would give patient maintenance, and on some of our trials, we use the standard of care, which is lenalidomide (Revlimid) maintenance. And we are also developing new approaches where we have done daratumumab (Darzalex) added once a month with lenalidomide. We have gone one year, and we have started to do two years of that. And after that, we would stop daratumumab and just do lenalidomide maintenance.

Lastly, to answer your question fully here, we would do a PET-CT in the bone marrow after the eight cycles as a repeat, and we would offer a patient to check on maintenance on an annual basis, and this is in accord with the NCCN guidelines. So a lot of details here, but you asked me how we do testing.

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Targeting of Myeloma Disease Progression and Bispecific Antibody Advantages

April 4, 2024/in MM Newly Diagnosed, MM Programs, MM START HERE, MM START HERE Webinar, MM Treatments and Clinical Trials, MM Videos ND, MM Videos TC, Multiple Myeloma /by Kara Rayburn

Targeting of Myeloma Disease Progression and Bispecific Antibody Advantages from Patient Empowerment Network on Vimeo.

How can myeloma progression and bispecific antibodies be used for myeloma care? Expert Dr. Ola Landgren from University of Miami Sylvester Comprehensive Cancer Center discusses how disease progression and genomic features can be targeted and the role that he perceives for bispecific antibodies in myeloma care.

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What Myeloma Patient Monitoring Occurs After Induction Therapy?

Is Myeloma Research Examining Sequencing of CAR T and Bispecifics?

What Are the Benefits of Myeloma Consults and Second Opinions?

Transcript:

Lisa Hatfield:

Dr. Landgren, what are the key biological processes driving disease progression and evolution of multiple myeloma, and how can we target these processes to prevent disease relapse and improve long-term outcomes?

Dr. Ola Landgren:

So that’s a very good question. So I think in a nutshell if you use genomics, which refers to the genetic changes that you can see in the plasma cells, there are certain features that the myeloma cells have. They have the copy number changes, that’s the gains and losses of chromosomes. You can find these if you do FISH and cytogenetics could be, for example, gain of chromosome 5 or gain of chromosome 7 or gain of chromosome 11. That would be part of the hyperdiploidy disease, or you have loss of chromosome 13 or 13q deletions. We also refer to 17p deletion. These are copy number changes, they’re extra or loss of these chromosomes. But then you have also the structural variance where you have the translocations of chromosome 14, chromosome 14 harbors the IGH locus, which regulates the making of immunoglobulins.

Plasma cells make immunoglobulins. For reasons that are not entirely clear. The translocations in myeloma that include IgH, they are partnering up with oncogenes. There is a list of oncogenes, there’s MATH, there’s three MATHs, A, B, C. There’s FGFR3, MMSET, and there’s also Cyclin D1 that are on the list. So these are the different types of structural variants that you can see with FISH probes. What people have understood less about are something called mutational signatures. And myeloma is made up by eight distinct mutational signatures that you can see in every single patient. And what that means is that you can, if you conduct whole genome sequencing and you look at all the base pairs, you can see there are certain number of combinations. C can be swapped for A and C can be swapped for G or C can be swapped for T, T can be A and T can be C and T can also be G.

Those are the combinations. So there are four different base pairs, but if you, because the DNA is double-stranded, these are the only possibilities that mathematically that you can see. Now if you look for every base pair and you look on one base pair on the left and one on the right, we call that 5 and 3 prime, you look through triplicates, every of these base pairs can have these different swaps I mentioned. Mathematically, there are 96 different combinations that you can come up with. That’s it.

If you don’t go through the entire genome from left to right, you see that there are these recurrent eight signatures that are there in every patient. So although we don’t understand why they are and exactly how they function, the fact that you see them in every patient tells us that this has to have something to do with the biology of the disease. It must have a role in the control of the disease. We are starting to see that there is one signature that’s called APOBEC. That signature seems to be very important for resistance to treatments. And you can see that APOBEC can be more or less expressed.

And if APOBEC is very expressed, we see that there are lot of mutations in the cells. We have seen in patients with the chemotherapy that APOBEC can be very expressed. When we treat with four drug combinations, it can be very expressed. And what I’m saying, when I say it can be expressed, these are in the patients that relapse out of these therapies. We have also seen that in CAR T cells and bispecifics. So that makes me believe and our group believe that the cells use some form of what we call tumor intrinsic defense mechanism to protect themselves from whatever therapy we use.

It doesn’t matter if it’s immunotherapy, chemotherapy or small molecule therapy, there are some fundamental programs the cells can turn on. We need to understand that better and we are spending a lot of time trying to drill into this. Lastly, I also want to say there was a fourth class of genomic events called complex events that you can see in myeloma, something called chromothripsis. That’s a very severe genomic lesion, is a ripple effect through the genome. There are a lot of havoc going on. And the first time we saw that, we thought this has to be something wrong with this sample. But when we look through more and more samples, we see that about a quarter of the patients actually have this chromothripsis.

So the bottom line is, it’s time to stop doing FISH, it’s time to do more advanced sequencing, ideally whole genome sequencing, but a step towards a whole genome could be to do whole exome sequencing. But there are companies saying that you can do whole genome sequencing for $1 in the future. So that’s really what needs to happen. We need to have better tools to better understand and then we can use this to better understand how to differentiate the therapy and have an individualized treatment. That’s what I talked about with the IRMA model.

Lisa Hatfield:

All right, well, thank you so much for that explanation. Dr. Landgren, can you speak to the advantages that bispecific antibodies offer over traditional therapies, and how do you see their role in overcoming treatment resistance?

Dr. Ola Landgren:

Well, the bispecific antibodies is a novel way of engaging the immune system to go after the myeloma. So if you think about the other antibodies we have, we have three other antibodies. We have daratumumab, we have isatuximab (Sarclisa), we have elotuzumab (Empliciti), they are naked antibodies. They bind to the myeloma and on the backend of these antibodies, there is something called the FC receptor that attracts cells, NK cells, for example, also T cells, and they also attract, some of these antibodies also attract complement and they also by themselves send what’s called a death signal into the myeloma cell.

The bispecific antibodies are very different. They bind and they don’t send death signals, they don’t engage with the complement. What they do is that they have another arm sticking out that binds to the T cells. That’s a CD3 arm and there’s an open pocket. So when a T cell passes by, it grabs the T cell. And now you have a T cell linked to the antibody sitting next to the myeloma cell and the T cell will kill the myeloma. T cells can be very aggressive and kill the myeloma. You just hold them together, it’s like a matchmaker.

And if you think about how CAR T-cell therapy is designed, you take out the T cells, you manufacture them to have a special antenna receptor on their surface, and then you give them back again. And then they bind, this receptor binds to myeloma cells. So in the setting of a CAR T-cell therapy, the T cell sits next to the myeloma cell, but that’s because the T cells were taken out of the body, manufactured to have this receptor that then finds the myeloma cell. But the bispecific antibody, that they don’t require the T cells to be taken out, to be modified this way.

You just use your existing T cells in your body and these antibody just binds to the T cells and the myeloma cells in the body. So it’s sort of a little bit mimics what the CAR T cells do, but it does it in its own way within the cell, within the tissue in the body. You asked me for resistance mechanism and how they are better. Well, I think the best answer I can give you is to say that the overall response rate for the bispecific antibodies are very high. They are 60 to 80 percent single drug compared to the current trials. And if you look and see the trials that have led to approval for the other existing drugs, they were 20 or 30 percent.

So the overall response rate is much higher for the bispecifics than they were for the other existing drugs. We don’t really know exactly how to use them, I would say. What’s the optimal dosing schedule? We give them weekly, it may be every other week, and maybe monthly, eventually, I would think. And should they be combined with which drugs? That’s ongoing investigation. Other questions are, can they be stopped? Can you monitor patients off therapy for a long time? Will some patients never have the disease coming back? We hope so, but we don’t know. Or would it be patients could be off therapy for a long time, like with CAR T cell? Could that happen with the bispecifics? It’s possible.

And if you were to monitor with blood-based tests and you see that there is reappearing disease, would you then put patients back on the therapy? These are questions we…there are a lot of questions, we don’t have answers to all these, but that’s where I think the field is going. A lot of people, including us, are trying to investigate this.

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What Are the Latest Artificial Intelligence Advancements for Myeloma?

April 4, 2024/in MM Newly Diagnosed, MM Programs, MM START HERE, MM START HERE Webinar, MM Treatments and Clinical Trials, MM Videos ND, MM Videos TC, Multiple Myeloma /by Kara Rayburn

What Are the Latest Artificial Intelligence Advancements for Myeloma? from Patient Empowerment Network on Vimeo.

What artificial intelligence advancements have emerged for myeloma? Expert Dr. Ola Landgren from University of Miami Sylvester Comprehensive Cancer Center discusses the IRMMa prediction model for myeloma care, factors that go into the IRMMaa model, and potential AI advancements for myeloma.

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Transcript:

Lisa Hatfield:

So that kind of leads to the next question that is really an exciting area. I know it’s not necessarily new, but newer is artificial intelligence. And I know I was reading an article about one of, that you and your colleagues have worked on a newer project and I don’t know if you pronounce it IRMMa or not, but using these large databases to help predict I think, it’s the response of treatment in some patients. So can you talk about that a little bit and tell us about that development and what developments are exciting with artificial intelligence in cancer, in particular myeloma?

Dr. Ola Landgren:

Yeah. So you mentioned the study we just published. We published a model that we call IRMMa and that stands for individual risk prediction for patients with multiple myeloma. So what we were thinking was at the current time, all the existing models are pretty much providing the average patient’s predicted outcome. So think about it is like it’s a probability measure.

So you say, if I take this about therapy, what’s the predicted average outcome for patients that take this therapy, say, five years later? So on average, say 70 percent of patients are free from progression. That sounds pretty good. The problem is that you don’t know if you are in the group, 70 percent group that didn’t progress or if you’re in the 30 percent that did progress.

So where are you as an individual? So it’s almost like looking at the weather app on your phone. If it says it’s a 70 percent probability of sunshine and then you go outside and it’s raining, it’s because it didn’t say that it’s 100 percent probability of sunshine. So if you think about another situation would be, say, in a GYN clinic, if a woman were to come and ask the doctor, am I pregnant? Yes or no? You couldn’t say it’s 70 percent probability. You would say, yes, you’re pregnant or not pregnant.

So for myeloma, we have for a long time been living in these weather report systems where we say 70 percent or 30 percent. And we want to go in the other direction of the pregnancy test, where we actually can say for someone with this particular disease profile, with this treatment, this is where this is going to take us. We worked on this project for almost four years, and we worked with a lot of other groups around the world that have a lot of data. And they have graciously agreed to collaborate with us and share their data sets. The beauty with this collaboration, there are many beauties of it, but one of them is that people don’t treat patients the same way.

And that actually has allowed us to say for patients that have a particular biological or genomic makeup, if you’re treated this way or that way or the other way or a fourth way and so forth, which of these different treatments would make patients have the longest progression and overall survival? So if you have a large database, you can actually ask those questions. So you can say that you profile individual patients in full detail and you put them in detailed buckets instead of grouping everybody together.

And now if you add a new case, if a new patient is being added and you say, which bucket would this individual fit? Well, this is the right biological bucket. You can then use this database to say out of all the different treatment options, which treatment option would last the longest, which would give the best overall survival? Other questions you could ask is also, for example, you have a patient with a certain biological workup or makeup. And you say, if I treat with these drugs, will the addition of, say, transplant, will that prolong progression for his survival?

And you can go into the database and the computer will then say, I have these many patients that have this genomic makeup and these many people that were treated with this treatment with transplant versus the same treatment without transplant. There was no difference in their progression or overall survival. So then the computer would say, it doesn’t add any clinical benefit, but there could be another makeup where the answer is opposite, but transplant actually would provide longer progression for his survival. I think the whole field of medicine is probably going to go more and more in this direction.

So what we want to do is to expand the number of cases. So we are asking other groups around the world, if they have data sets with thousands of patients, they could be added to this database and we could then have more and more detailed information on sub-types of disease and more and more treatment. So it will be better as we train it with larger data sets. The model is built as an open interface so we can import new data. And that’s also important because the treatments will continue to change. So we, for example, say I have a patient that has this genetic makeup. I was thinking of using a bispecific antibody for the newly diagnosed setting.

How is that going to work? The computer will say, I don’t know, because we don’t have any patients like that in the database because that’s not the data, type of data that currently exists from larger studies. But let’s say in the future, if there were datasets like that, you could ask the computer and the computer will tell you what the database finds as the answer. But if you go for another combination, if that’s in the database, it would answer that too. That is where I think the field is going.

And lastly, I would say we are also using these types of technologies to evaluate the biopsies, the material. We work with the HealthTree Foundation on a large project where we are trying to use computational models to get out a lot of the biological data out of the biopsies and also to predict outcomes. So I think artificial intelligence is going to come in so many different areas in the myeloma field and probably in many, many other fields in medicine.

Lisa Hatfield:

Yeah, that’s wonderful. So if you have a newly diagnosed patient coming in to see you, do you use this model and explain to them what came back to you? Or is it right now just collecting the data for this dataset?

Dr. Ola Landgren:

So at the current time, we have to be cautious. We cannot promise things that we cannot deliver. So we have clearly said this is a research tool. It was just published less than a month ago in the Journal of Clinical Oncology. It is publicly available. The paper is available. Anyone can go there and download the paper and anyone can also in this paper find there’s a website. You can actually see the database as well. And there is a lot of corresponding material online on how to interpret. So for now, it is a research tool. But I think it’s possible in the future that we would start considering using it. And if other people find it useful, maybe they will do that, too. But for now, it is a research tool.

Lisa Hatfield:

As a patient, I would be very intrigued with that and what might come back. Just like you said, it’s a tool to maybe help identify new treatments or whatever. I did ask ChatGPT if there’s a cure for myeloma, if there will be one in the next 10 years. I didn’t really love the answer. It was a little bit vague. But yeah, I like looking into AI a little bit and ChatGPT and all that. So thank you so much for that overview.

Dr. Ola Landgren:

This is exactly like ChatGPT. It works the same way, but it’s only centered around multiple myeloma. For now, the way we have done it is that we have to start somewhere. As I told you, it’s a four-year work effort with a lot of people. We have like 10, 15 people working day and night on this project. So we started on the newly diagnosed patients. But we intend to scale it up. We intend to build in a lot of new features. And, of course, we want to add more datasets to it. And last thing I want to say to you, I find it very, very fascinating how you can, as a human being, as a researcher, you can ask the computer, and it will give you answers back that you didn’t think about yourself.

So you talk about ChatGPT. So we are using our model. We can have the model looking at biopsies. We can ask the computer, what is this biopsy? What’s going on? And the computer will say this and this and this genetic feature is going on. And then we ask the question, how did you conclude that? And then the computer will say, look here. So it would then label areas in the biopsy and say, I looked here. It doesn’t yet tell us what it found, but it tells us where it found it or where it looked to come to its conclusion.

So when it finds the right conclusion, we are looking in these areas to see what’s going on in these areas and how does it look different from other areas or in other samples. So having a dialogue with the computer can give us new insight. It’s almost like taking a young kid and you go out for a walk and you look and you see a lot of buildings and the kid looks down and looks and finds a little flower on the ground. And you say, oh, my gosh, I missed that one. The kid would not miss it. The computer is the same way.

Lisa Hatfield:

Yeah, that’s a great analogy, too. And I think we could have a 10-hour conversation about that, particularly with myeloma, because it’s so complicated, complex. So I hope we can in the future again talk about that.

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What Are the Benefits of Myeloma Consults and Second Opinions?

April 4, 2024/in MM Newly Diagnosed, MM Programs, MM START HERE, MM START HERE Webinar, MM Treatments and Clinical Trials, MM Videos ND, MM Videos TC, Multiple Myeloma /by Kara Rayburn

What Are the Benefits of Myeloma Consults and Second Opinions? from Patient Empowerment Network on Vimeo.

What can myeloma consults and second opinions bring to patients? Expert Dr. Ola Landgren from University of Miami Sylvester Comprehensive Cancer Center discusses the benefits of consults, second opinions, and myeloma specialist centers.

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See More from START HERE Myeloma

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Targeting of Myeloma Disease Progression and Bispecific Antibody Advantages

Is Myeloma Research Examining Sequencing of CAR T and Bispecifics?

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Transcript:

Lisa Hatfield:

I’m going to segue into a comment that I always make to myeloma patients. As Dr. Landgren was explaining all of these treatment options, he is on top of all the latest and greatest news and therapies. I always recommend to myeloma patients newly diagnosed or otherwise to seek out at least one consult from a specialist. If you have difficulty accessing care, then a lot of places can do video conferencing, but even that one consult to see a myeloma specialist is so important in your care and treatment options. So I’ll just throw that out there, Dr. Landgren, as a myeloma specialist that you are, we appreciate your expertise in explaining that so well.

Dr. Ola Landgren:

I agree 100 percent with what you said, and I would like to add to that and say, going to a specialist center and it doesn’t have to be here, can really really help. It can be a lot of small things. There is data indicating that survival is longer for patients who have access to specialists. That has been published in the Journal of Clinical Oncology. The Mayo Clinic has published that, I think it was more than one year longer survival.

That by itself is, of course, very strong, but I also think that there are a lot of the small things like the different types of pre-medications, the drugs that are given around myeloma drugs. Could you decrease the dose of some of these drugs like the dexamethasone (Decadron)? Could you get rid of Benadryl if you give the antibodies? These may look as small things, but they can make a huge difference for quality of life.

We have a lot of people coming for second opinions, and we always say if you live closer to someone that you trust, you should go back and be treated there. You can always reach out to us. We are happy to be involved. You have us as a backup. We can be your quarterback if you ever need us. I think that is absolutely the best advice for every patient. Go and get feedback and if you’re not sure about the feedback you get, you could always have two different quarterbacks and you could ask them. I don’t think having 10 or 20 is going to help, but having one or two second opinions, I think is a good decision.

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Myeloma Patient Expert Q&A: Dr. Ola Landgren

April 2, 2024/in MM Newly Diagnosed, MM Programs, MM START HERE, MM START HERE Webinar, MM Treatments and Clinical Trials, MM Videos ND, MM Videos TC, Multiple Myeloma /by Kara Rayburn

Myeloma Patient Expert Q&A: Dr. Ola Landgren from Patient Empowerment Network on Vimeo.

START HERE bridges the gap between expert and patient voices, empowering myeloma patients to feel comfortable asking precise questions of their healthcare team.

In this webinar, Dr. Ola Landgren delves into the emerging and exciting therapies and clinical trials for myeloma, discusses the latest options for relapsed disease, and explores the current landscape of managing and monitoring multiple myeloma. Watch as Dr. Landgren answers patient-submitted questions and discusses another hot topic: the utilization of artificial intelligence in multiple myeloma.

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Transcript:

Lisa Hatfield:

Hello, and welcome. My name is Lisa Hatfield, your host for this Patient Empowerment Network START HERE program where we bridge the expert and patient voice to enable you and me to feel comfortable asking questions of our healthcare teams. The world is complicated, but understanding your multiple myeloma doesn’t have to be. The goal of this program is to create actionable pathways for getting the most out of myeloma treatment and survivorship.

Today I am honored and really excited to be joined by Dr. Ola Landgren. Dr. Landgren is chief in the Division of Myeloma and the Department of Medicine, and also serves as director of the Sylvester Myeloma Institute at the University of Miami’s Miller School of Medicine. Dr. Landgren, it’s such a pleasure having you today.

Dr. Ola Landgren:

Thank you very much for having me. It’s really a great pleasure to be here today.

Lisa Hatfield:

So in this program, first, we’ll get a high level update from Dr. Landgren on what the latest myeloma news means for you and your family. And then we will launch into some questions that we’ve received from you. Dr. Landgren. We’re at a pivotal moment in the history of multiple myeloma. We’re experiencing an unprecedented wave of progress marked by significant increase in new treatment options and ongoing research. We are very honored to have your expertise to guide us in understanding these advancements and providing clarity around all the evolving landscape of myeloma care.

So before we get started, to you at home, would you please remember to download the program resource guide via the QR code. This is where you’ll find useful information to follow before the program and after. So we are ready to START HERE. Dr. Landgren, can you speak to the emerging and exciting myeloma therapies and trials right now?

Dr. Ola Landgren:

I’ll do my best. There are so many things to talk about, and I don’t think we have 10 hours, so I will have to shorten it. But I would say that the past 12 to 18 months, we have had three new drugs approved in the field of myeloma. These are the bispecific antibodies. The first out of those three was the BCMA-CD3 targeted drug teclistamab-cqyv (Tecvayli). And in the middle of 2023, we had both talquetamab-tgvs (Talvey), and elranatamab-bcmm (Elrexfio) approved. Talquetamab has another target is GPRC5D with CD3. And elranatamab is similar to teclistamab with the BCMA-CD3 targeted bispecific antibody. These are amazing drugs. They have been found in patients that have been heavily pretreated to result in about 60 percent or more percent of patients responding.

So overall response rates ranging from 60 percent to 80 percent in various trials. We have now these drugs approved, they’re still only approved as single drug and there are new trials going, combinations of two of these or these drugs with other drugs such as daratumumab (Darzalex) or IMiDs, such as lenalidomide (Revlimid) or pomalidomide (Pomalyst). So a lot of drug development is ongoing as we speak. We also have the CAR T cells that are reasonably new drugs. We, you think about everything new every week there’s a new drug, but they are very new CAR T cells.

We have had them for about three or so years, three-and-a-half years. And, the two drugs that are approved in that setting is, ide-cel (idecabtagene vicleucel) [Abecma]. That was the first and then cilta-cel (ciltacabtagene autoleucel) [Carvykti], that was the second. They both go after BCMA similar to the two antibodies I mentioned, teclistamab and elranatamab because they are CAR T cells, that indicates that they are cells.

They come from the same person who’s going to receive them back as treatment. So you collect the cells from the blood and you manufacture them into to CAR cells. So chimeric antigen receptor T cells, and then you give them back. There are several new CAR T-cells in development. There are other targets in development, GPRC5D, for example. There are additional other targets and there are also dual targeted cell therapies in development.

There are also allogeneic CAR T cells in development and that means that you could have a product off the shelf. So someone could donate cells, they could be manufactured into CAR T cells, and then you could give them to technically any person, so it doesn’t have to be the same person collecting and then manufacturing, giving them back. So that would shorten the time window for production.

And there are a lot of other details also that are important in this context. The whole manufacturing process that’s currently four to six weeks is being improved. There are some technologies that can make the CAR T cells in 48 hours, but the turnaround time is maybe one to two weeks with all the control steps, but that’s still a huge improvement. And then you have the antibody drug conjugate if you want.

So then you have the belantamab mafodotin (Blenrep). That actually was the first BCMA targeted therapy we had in myeloma. And then the drug was approved on an accelerated approval study. But when the randomized study was completed, it turned out that it was not better than the control arm. The company took it off the market. And now what’s happening is that there are two new trials, and one of them was just reported in the beginning of February of 2024.

The other one was around the ASH meeting in 2023. These two trials show that if you combine it with other drugs, the most recent one was with bortezomib-dexamethasone (Velcade-Decadron), that was superior with the belantamab mafodotin with bortezomib-dexamethasone versus daratumumab with bortezomib-dexamethasone. So I think we will probably see this drug coming back to the myeloma field. It is currently available as compassionate use, so physicians can prescribe it, but these trials will most likely, I would think, lead to FDA approvals with these combinations.

And lastly, I would say that other exciting trials, there are so many trials going on, but another thing that I think is interesting and exciting is also the use of antigens. And you can use mRNA and things like that. So these are like the vaccines. You can either, take a patients’ myeloma cells and look what they have on the surface, you can make more traditional vaccines or you can use more sophisticated newer technologies just like how the COVID vaccines were developed. And you can inject these sequences and then they will translate into spike proteins where the immune system could go after myeloma cells.

We don’t yet have a product like that in the myeloma field, but there are a lot of biotech and groups that are working to see. Moderna, was actually initially a cancer vaccine company and then COVID came and they turned into a COVID company, and now they’re be back again in the cancer field. So that’s a little bit of a summary of a lot of the exciting news that’s out there.

Lisa Hatfield:

Thank you. And do you have any comments about the sequencing of some of these? So with both CAR T and some of the bispecifics approved, obviously if a patient comes in and they need something right away, they’ll take whatever is first available. But all things being equal, if a patient says, well, I can, I have both CAR T accessible and bispecifics accessible. There are some patients out there, I’ve spoken with some who are wondering, is there a benefit to sequencing one before the other, or are there any trials looking into that?

Dr. Ola Landgren:

There are studies that have allowed patients to go on treatment with one of these modalities. For example, the bispecific antibodies with the prior exposure to a CAR T-cell therapy. There are also trials with CAR T-cell therapy that has allowed patients who have been exposed to prior antibodies, either bispecifics or the conjugated antibody drug conjugates, Belantamab mafodotin. So if you look at those studies and see how the numbers compare, if you are not exposed or you are exposed, I think the data is not entirely clear-cut.

There is no definitive study. Some data suggests that maybe it’s not that different, but then there are some studies that suggest that if you go to the antibody first that maybe that would lower the efficacy of the CAR T cell. So some people have for that reason said the CAR T cell should be done first. To make it even more complicated, there are some studies that have then taken time into the equation. So that means that you could have the patient treated with the antibodies for BCMA and CD3, and the antibody is given successfully for a long time, for many years. And eventually, unfortunately, the antibody may stop working.

Now, if you switch back to back to a CAR T-cell therapy without any other therapy in between, some studies indicate that that’s less likely to be beneficial. But if you instead do another target, say you did GPRC5D/CD3, or you did a completely different therapy with small molecules or you did carfilzomib (Kyprolis), or you did venetoclax (Venclexta), or IMiDs, or different types of combinations that are out there, been around for a long time, and you get good mileage out of those combinations.

Now, if that stops working, if you now go to this other therapy, you go back to the CAR T cell, that will suggest that the results are not that different. So I think that there are aspects that we don’t fully understand. I personally believe, based on what I’ve seen, based on what I know from treating thousands of patients with myeloma for almost 30 years I’ve been a doctor, I think time is probably very, very important. So if you go back to back from one therapy to the other, that’s less likely to be beneficial. If you go from one therapy, and it stops working and go to the other drug with the same target.

But I would say it’s not that different from how we think about IMiDs or proteasome inhibitors. If you were to go single drug with a proteasome inhibitor and you switch to single drug with another proteasome inhibitor, or the same thing with an IMiD, that’s less likely to work versus if you went to something else in between. So we just need to generate more data and learn. Lastly, I want to say that in my experience, from all I see in my clinic at the current time, I think the choice that patients make is based on personal preference and to some degree also the situation of the patient. I saw a patient yesterday, 50 years old, who came from another country and has relocated to us here in Miami and asked, what are the options?

And we talked about CAR T cells, we talked about bispecifics. And considering all the different factors that CAR T cell would imply that we had to give some other combination therapy for two or three cycles while we harvest the CAR T cells and manufacture the CAR T cells and then plan for the admission and give it, and also that the patient was not really very happy about the side effects in the hospital with CAR T cell. That patient shows the bispecific, but I’ve also seen other patients in the same situation saying, I’d rather do these different steps for two or three months, I stay in the hospital, and then I enjoy being off therapy.

Actually, I saw another patient just a few days ago, a gentleman in his upper 70s who we had the same conversation, and he had picked the CAR T cells. And I saw him with his wife and he has been off treatment for two years doing excellent. So different patients make different decisions. And I think that is just how the field is evolving. So I think we should be open to individual patient’s priorities and what they want, and we should just offer everything. And of course, we can guide if a patient wants us to give direction, but I think presenting it and let patients be part of the decision-making, that’s the future of how medicine should be practiced.

Lisa Hatfield:

Thank you so much for that explanation. I’m going to segue into a comment that I always make to myeloma patients. As Dr. Landgren was explaining all of these treatment options, he is on top of all the latest and greatest news and therapies. I always recommend to myeloma patients newly diagnosed or otherwise to seek out at least one consult from a specialist. If you have difficulty accessing care, then a lot of places can do video conferencing, but even that one consult to see a myeloma specialist is so important in your care and treatment options. So I’ll just throw that out there, Dr. Landgren, as a myeloma specialist that you are, we appreciate your expertise in explaining that so well.

Dr. Ola Landgren:

I agree 100 percent with what you said, and I would like to add to that and say, going to a specialist center and it doesn’t have to be here, can really really help. It can be a lot of small things. There is data indicating that survival is longer for patients who have access to specialists. That has been published in the Journal of Clinical Oncology. The Mayo Clinic has published that, I think it was more than one year longer survival.

That by itself is, of course, very strong, but I also think that there are a lot of the small things like the different types of pre-medications, the drugs that are given around myeloma drugs. Could you decrease the dose of some of these drugs like the dexamethasone? Could you get rid of Benadryl if you give the antibodies? These may look as small things, but they can make a huge difference for quality of life.

We have a lot of people coming for second opinions, and we always say if you live closer to someone that you trust, you should go back and be treated there. You can always reach out to us. We are happy to be involved. You have us as a backup. We can be your quarterback if you ever need us. I think that is absolutely the best advice for every patient. Go and get feedback and if you’re not sure about the feedback you get, you could always have two different quarterbacks and you could ask them. I don’t think having 10 or 20 is going to help, but having one or two second opinions, I think is a good decision.

Lisa Hatfield:

That’s really helpful information, thank you, Dr. Landgren. So I think we’re going to shift a little bit to managing and monitoring multiple myeloma. Once you’ve had a patient go through the induction therapy, what kind of monitoring do you complete for your myeloma patients and in particular those who have reached a certain level response and are maybe on maintenance or continuous therapy, what type of tests do you do and how often regarding labs, imaging, bone marrow biopsies?

Dr. Ola Landgren:

There are a lot of different ways, obviously, of practicing medicine. So every center has developed models that they feel very comfortable doing. So I like details. I like to know things. I like to check things. I’m not excessive in ordering invasive tests, but I like to know. Also, I like to make sure the patient not only has good long-term clinical outcomes, but also good quality of life. And to me, I try to minimize the intrusiveness of what we do. So, for example, if I give a combination therapy where there is an injection or infusion, say week one, week two, week three, and then there is a week off. I recognize that if you do labs during that week off, you will have a better yield and understanding of how these three different injections or infusions actually have moved the disease forward and suppressed the disease.

But in my mind, I think that week off is a very important week off for the patient. So I would rather do testing the third day of the treatment at the treatment unit. So if it’s week one, week two, week three, I would draw the myeloma labs that same day. And that would give the patient six more days off from injection, infusion that third week and the whole fourth week off. So I would give the patient 13 days off.

Again, these are small things. These are things I’ve thought about a lot. I’ve practiced medicine for many years and I recognize that having time off like that, many patients travel, they go on vacation, they do different things. So I don’t want to just randomly put a blood test in the fourth week just because I want to check after week one, two, three, and then have the assessment.

I sort of underestimate the benefit of the therapy and then I start the next cycle, say back to back cycle two and cycle three and so forth. I would typically do blood tests once a month following these principles. I do baseline and I would do the last day of injection or infusion. For a newly diagnosed patient, you ask me, I would for baseline always do bone marrow biopsy and an aspirate. I would always do a PET-CT for every patient as my default. Sometimes we end up doing MRI. So that could be other things that are happening, but that is what we do for the majority of our patients.

After we have completed four to six cycles of treatment for patients that are candidates for consideration of transplant with chemotherapy with melphalan (Alkeran), we would usually do a biopsy after four to six cycles and we would use that to determine what’s the optimal mobilization protocol for stem cells. When we do that, we would run a MRD test.

We would run our in-house flow cytometry test that we developed when I used to work at Sloan Kettering and we have developed that here in Miami as well. We work closely with Sloan Kettering, and we have set up this assay in collaboration in the new 2.0 version. We will also send the aspirate for the clonoSEQ at Adaptive Biotech, which is the DNA-based sequencing for MRD. We would send the patient for collection of stem cells.

When the patient is back, we will continue treating. So if you say we do it after four cycles, we would collect, if we do it after five or six, then we collect. After that, we would typically resume therapy and for the majority of our patients, we actually give around eight cycles of therapy, and we have seen that you can deepen the response. You don’t increase the toxicity, but you deepen the response for the vast, vast majority of our patients. When we have used our best therapies, we have done it that way…

We have even published on this, over 70 percent of our patients are MRD negative, and many of those patients, when they come to cycle eight, they ask, do I have to do the transplant? And that is a controversial topic. But I think there are two large randomized trials that have shown the same thing, that there is no survival benefit with transplant. But you can also say that there is, in those two trials, a progression free survival benefit, meaning that the disease would stay way longer with transplant.

But many patients say, if I reach MRD-negative, both those two trials show that if you’re MRD-negative without transplant, or you’re MRD-negative with the transplant, PFS was actually the same. And given that there is no survival, overall survival benefit, why would I subject myself to go to that? Why don’t I keep the cells in the freezer and go right to maintenance? And we will have a conversation with every patient, they would meet our transplant team, they would meet our myeloma expert team.

And the individual patient will make decisions. I think over time, more and more patients have chosen to keep the cells in the freezer. For patients that are MRD-positive, we would counsel towards transplant, but there are patients that don’t want to do that, and we are not forcing any patients to do that. We would give patient maintenance, and on some of our trials, we use the standard of care, which is lenalidomide maintenance.

And we are also developing new approaches where we have done daratumumab added once a month with lenalidomide. We have gone one year, and we have started to do two years of that. And after that, we would stop daratumumab and just do lenalidomide maintenance. Lastly, to answer your question fully here, we would do a PET-CT in the bone marrow after the eight cycles as a repeat, and we would offer a patient to check on maintenance on an annual basis, and this is in accord with the NCCN guidelines. So a lot of details here, but you asked me how we do testing.

Lisa Hatfield:

Yes. And one of the questions that comes up, too, regarding bone marrow biopsy, so you talked about patients kind of through the process of myeloma treatment, perhaps they’ve reached a point where they’re going to be for a while. Do you see a need for continued bone marrow biopsy, say, annually, or is there some benefit to using the newer tests that are being investigated, like mass spec testing and some of the newer ones, I think the EuroFlow? Do you think that that can be used to test for bone marrow biopsy? And how will that be used to monitor the myeloma if a patient is doing relatively well, or do you still like to do bone marrow biopsies on a regular basis? And I know every specialist is different in how they’ll answer that question.

Dr. Ola Landgren:

So what’s known in the literature is that there is no study that definitively has compared annual biopsies with these blood-based tests that you mentioned, showing that they can replace the bone marrow. Those tests or those studies have not yet been published and shown in a convincing way that we have done. This is how it is. It’s still an open question. We don’t know the answer for sure. So our take has been to offer patients to repeat it on an annual basis for maybe two or three and sometimes up to five years. I don’t think we would do biopsies every year for five, 10, 15 or more years. At some point, you have to ask yourself, what are we trying to chase here?

But I think the data we’re looking at that we have published on this and others have also show that if you are MRD-negative after completion of the eight cycles with or without the transplant, the patient that are MRD-negative one year later, they are more likely to be free from progression 10 years later, compared to the ones where you only check once and you don’t know what happened one year later. And that is frankly because there is a small group of patients where MRD-negative could bounce back into positive.

So to check after completion after eight cycles and to check after one more year on maintenance, I think gives us more confidence in thinking about if we eventually could step down and maybe even stop the maintenance at the long term. There is no study that definitively has proven that, but the data suggests that being negative after eight and do another year and even if you do two years out, those are very strong indicators that the disease will stay away long term.

So that’s our justification for offering it, but we would never force any patient. And I also want to say that we have thought about for a long time, how we can contribute to the field and how we can advance the field for blood-based tests. So we are here in Miami, developing a lot of these technologies, and I have made a promise that we will make all these available for all patients that come here to Miami as part of our standard workup. Because they are not clinically validated tests, they will have to be reported for now as research tests, but we will share the information with individual patients.

So we have three different platforms for now. And we are working on the fourth one. So one of them is the mass spec with MALDI, where we can screen the blood with lasers. And we can increase the sensitivity by maybe hundred times compared to existing immunofixation assays. The second is something called clonotypic peptides, which is a more sophisticated way to run mass spec, which is probably up to thousand times more sensitive than immunofixation. And the third technology we are doing or setting up right now is circulating cells that we sequence.

And this is the Menarini technology that is approved for certain other solid tumors. I think for GI malignancies, it’s FDA cleared, but we are doing it in myeloma. We are also looking for free circulating DNA. We’re working with New York Genome Center to set those types of assays up. So my thinking is, if we can offer every patient that come here to do it, and many of those patients will do an annual biopsy, we actually will have the database that can answer the question you asked me, if it can replace. There is no other way that this can ever be answered.

But having a large database, we actually can compare on a patient level, how the bone marrow biopsy with flow cytometry and sequencing, how that behaves in relation to the blood base. How does it perform? Is any of these better? Can they replace each other? So I think if we do this for one or two years, we will have the answer to the question. That’s why I want to do it.

Lisa Hatifeld:

So that kind of leads to the next question that is really an exciting area. I know it’s not necessarily new, but newer is artificial intelligence. And I know I was reading an article about one of, that you and your colleagues have worked on a newer project and I don’t know if you pronounce it IRMMa or not, but using these large databases to help predict I think, it’s the response of treatment in some patients. So can you talk about that a little bit and tell us about that development and what developments are exciting with artificial intelligence in cancer, in particular myeloma?

Dr. Ola Landgren:

Yeah. So you mentioned the study we just published. We published a model that we call IRMMa and that stands for individual risk prediction for patients with multiple myeloma. So what we were thinking was at the current time, all the existing models are pretty much providing the average patient’s predicted outcome. So think about it is like it’s a probability measure. So you say, if I take this about therapy, what’s the predicted average outcome for patients that take this therapy, say, five years later? So on average, say 70 percent of patients are free from progression. That sounds pretty good. The problem is that you don’t know if you are in the group, 70 percent group that didn’t progress or if you’re in the 30 percent that did progress.

So where are you as an individual? So it’s almost like looking at the weather app on your phone. If it says it’s a 70 percent probability of sunshine and then you go outside and it’s raining, it’s because it didn’t say that it’s 100 percent probability of sunshine. So if you think about another situation would be, say, in a GYN clinic, if a woman were to come and ask the doctor, am I pregnant? Yes or no? You couldn’t say it’s 70 percent probability. You would say, yes, you’re pregnant or not pregnant.

So for myeloma, we have for a long time been living in these weather report systems where we say 70 percent or 30 percent. And we want to go in the other direction of the pregnancy test, where we actually can say for someone with this particular disease profile, with this treatment, this is where this is going to take us. We worked on this project for almost four years and we worked with a lot of other groups around the world that have a lot of data. And they have graciously agreed to collaborate with us and share their data sets. The beauty with this collaboration, there are many beauties of it, but one of them is that people don’t treat patients the same way.

And that actually has allowed us to say for patients that have a particular biological or genomic makeup, if you’re treated this way or that way or the other way or a fourth way and so forth, which of these different treatments would make patients have the longest progression and overall survival? So if you have a large database, you can actually ask those questions. So you can say that you profile individual patients in full detail and you put them in detailed buckets instead of grouping everybody together.

And now if you add a new case, if a new patient is being added and you say, which bucket would this individual fit? Well, this is the right biological bucket. You can then use this database to say out of all the different treatment options, which treatment option would last the longest, which would give the best overall survival? Other questions you could ask is also, for example, you have a patient with a certain biological workup or makeup. And you say, if I treat with these drugs, will the addition of, say, transplant, will that prolong progression for his survival?

And you can go into the database and the computer will then say, I have these many patients that have this genomic makeup and these many people that were treated with this treatment with transplant versus the same treatment without transplant. There was no difference in their progression or overall survival. So then the computer would say, it doesn’t add any clinical benefit, but there could be another makeup where the answer is opposite, but transplant actually would provide longer progression for his survival. I think the whole field of medicine is probably going to go more and more in this direction. So what we want to do is to expand the number of cases.

So we are asking other groups around the world, if they have data sets with thousands of patients, they could be added to this database and we could then have more and more detailed information on sub types of disease and more and more treatment. So it will be better as we train it with larger data sets. The model is built as an open interface so we can import new data. And that’s also important because the treatments will continue to change. So we, for example, say I have a patient that has this genetic makeup. I was thinking of using a bispecific antibody for the newly diagnosed setting.

How is that going to work? The computer will say, I don’t know, because we don’t have any patients like that in the database because that’s not the data, type of data that currently exists from larger studies. But let’s say in the future, if there were datasets like that, you could ask the computer and the computer will tell you what the database finds as the answer. But if you go for another combination, if that’s in the database, it would answer that too. That is where I think the field is going.

And lastly, I would say we are also using these types of technologies to evaluate the biopsies, the material. We work with the HealthTree Foundation on a large project where we are trying to use computational models to get out a lot of the biological data out of the biopsies and also to predict outcomes. So I think artificial intelligence is going to come in so many different areas in the myeloma field and probably in many, many other fields in medicine.

Lisa Hatfield:

Thank you so much, Dr. Landgren, for that broad overview of myeloma, especially relapsed and refractory myeloma. So it’s that time now where we answer questions we’ve received from you. Please remember that this is not a substitute for medical care. Always consult with your medical team. And we’re going to jump right into some questions that we’ve received from patients, Dr. Landgren, if you have a little bit of time to answer these questions for us.

Dr. Ola Landgren:

Of course.

Lisa Hatfield:

Okay. So broad questions. We try to make them broad so they apply to most people, but this patient is asking Dr. Landgren, what are the key biological processes driving disease, progression and evolution of multiple myeloma, and how can we target these processes to prevent disease relapse and improve long-term outcome?

Dr. Ola Landgren:

So that’s a very good question. So I think in a nutshell if you use genomics, which refers to the genetic changes that you can see in the plasma cells, there are certain features that the myeloma cells have. They have the copy number changes, that’s the gains and losses of chromosomes. You can find these if you do FISH and cytogenetics could be, for example, gain of chromosome 5 or gain of chromosome 7 or gain of chromosome 11. That would be part of the Hyperdiploidy disease, or you have loss of chromosome 13 or 13q deletions. We also refer to 17p deletion. These are copy number changes, they’re extra or loss of these chromosomes. But then you have also the structural variance where you have the translocations of chromosome 14, chromosome 14 harbors the IGH locus, which regulates the making of immunoglobulins.

Plasma cells make immunoglobulins. For reasons that are not entirely clear. The translocations in myeloma that include IgH, they are partnering up with oncogenes. There is a list of oncogenes, there’s MATH, there’s three MATHs, A, B, C. There’s FGFR3, MMSET, and there’s also Cyclin D1 that are on the list. So these are the different types of structural variants that you can see with FISH probes.

What people have understood less about are something called mutational signatures. And myeloma is made up by eight distinct mutational signatures that you can see in every single patient. And what that means is that you can, if you conduct whole genome sequencing and you look at all the base pairs, you can see there are certain number of combinations. C can be swapped for A and C can be swapped for G or C can be swapped for T, T can be A and T can be C and T can also be G.

Those are the combinations. So there are four different base pairs, but if you, because the DNA is double stranded, these are the only possibilities that mathematically that you can see. Now if you look for every base pair and you look on one base pair on the left and one on the right, we call that 5 and 3 prime, you look through triplicates, every of these base pairs can have these different swaps I mentioned. Mathematically, there are 96 different combinations that you can come up with. That’s it.

If you don’t go through the entire genome from left to right, you see that there are these recurrent eight signatures that are there in every patient. So although we don’t understand why they are and exactly how they function, the fact that you see them in every patient tells us that this has to have something to do with the biology of the disease. It must have a role in the control of the disease. We are starting to see that there is one signature that’s called APOBEC. That signature seems to be very important for resistance to treatments. And you can see that APOBEC can be more or less expressed.

And if APOBEC is very expressed, we see that there are lot of mutations in the cells. We have seen in patients with the chemotherapy that APOBEC can be very expressed. When we treat with four drug combinations, it can be very expressed. And what I’m saying, when I say it can be expressed, these are in the patients that relapse out of these therapies. We have also seen that in CAR T cells and bispecifics. So that makes me believe and our group believe that the cells use some form of what we call tumor intrinsic defense mechanism to protect themselves from whatever therapy we use.

It doesn’t matter if it’s immunotherapy, chemotherapy or small molecule therapy, there are some fundamental programs the cells can turn on. We need to understand that better and we are spending a lot of time trying to drill into this.

Lastly, I also want to say there was a fourth class of genomic events called complex events that you can see in myeloma, something called chromothripsis. That’s a very severe genomic lesion, is a ripple effect through the genome. There are a lot of havoc going on. And the first time we saw that, we thought this has to be something wrong with this sample. But when we look through more and more samples, we see that about a quarter of the patients actually have this chromothripsis.

So the bottom line is, it’s time to stop doing FISH, it’s time to do more advanced sequencing, ideally whole genome sequencing, but a step towards a whole genome could be to do whole exome sequencing. But there are companies saying that you can do whole genome sequencing for $1 in the future. So that’s really what needs to happen. We need to have better tools to better understand and then we can use this to better understand how to differentiate the therapy and have an individualized treatment. That’s what I talked about with the IRMA model.

Lisa Hatfield:

All right, well, thank you so much for that explanation. Dr. Landgren, can you speak to the advantages that bispecific antibodies offer over traditional therapies and how do you see their role in overcoming treatment resistance?

Dr. Ola Landgren:

Well, the bispecific antibodies is a novel way of engaging the immune system to go after the myeloma. So if you think about the other antibodies we have, we have three other antibodies. We have daratumumab, we have isatuximab (Sarclisa), we have elotuzumab (Empliciti), they are naked antibodies. They bind to the myeloma and on the backend of these antibodies, there is something called the FC receptor that attracts cells, NK cells, for example, also T cells, and they also attract, some of these antibodies also attract complement and they also by themselves send what’s called a death signal into the myeloma cell.

The bispecific antibodies are very different. They bind and they don’t send death signals, they don’t engage with the complement. What they do is that they have another arm sticking out that binds to the T cells. That’s a CD3 arm and there’s an open pocket. So when a T cell passes by, it grabs the T cell. And now you have a T cell linked to the antibody sitting next to the myeloma cell and the T cell will kill the myeloma. T cells can be very aggressive and kill the myeloma. You just hold them together, it’s like a matchmaker.

And if you think about how CAR T-cell therapy is designed, you take out the T cells, you manufacture them to have a special antenna receptor on their surface, and then you give them back again. And then they bind, this receptor binds to myeloma cells. So in the setting of a CAR T-cell therapy, the T-cell sits next to the myeloma cell, but that’s because the T cells were taken out of the body, manufactured to have this receptor that then finds the myeloma cell. But the bispecific antibody, that they don’t require the T cells to be taken out, to be modified this way.

You just use your existing T-cells in your body and these antibody just binds to the T cells and the myeloma cells in the body. So it’s sort of a little bit mimics what the CAR T cells do, but it does it in its own way within the cell, within the tissue in the body. You asked me for resistance mechanism and how they are better. Well, I think the best answer I can give you is to say that the overall response rate for the bispecific antibodies are very high. They are 60 to 80 percent single drug compared to the current trials. And if you look and see the trials that have led to approval for the other existing drugs, they were 20 or 30 percent.

So the overall response rate is much higher for the bispecifics than they were for the other existing drugs. We don’t really know exactly how to use them, I would say. What’s the optimal dosing schedule? We give them weekly, it may be every other week, and maybe monthly, eventually, I would think. And should they be combined with which drugs? That’s ongoing investigation. Other questions are, can they be stopped? Can you monitor patients off therapy for a long time? Will some patients never have the disease coming back? We hope so, but we don’t know. Or would it be patients could be off therapy for a long time, like with CAR T cell? Could that happen with the bispecifics? It’s possible.

And if you were to monitor with blood-based tests and you see that there is reappearing disease, would you then put patients back on the therapy? These are questions we…there are a lot of questions, we don’t have answers to all these, but that’s where I think the field is going. A lot of people, including us, are trying to investigate this.

Lisa Hatfield:

Okay, thank you. And we have a number of questions about MRD testing, so I’m going to try to combine those all together. Basically, what the questions are asking is how do you interpret MRD testing with regard to prognosis, treatment response, and maybe even like treatment, ongoing treatment? How do you use those results in your clinic or any comments you might have on the MRD test?

Dr. Ola Landgren:

So MRD tests have been around for quite some time. We have been pioneers pushing it. We have worked on it for over 15 years. We worked with the FDA to see if MRD could eventually become an endpoint for drug approval, that’s work in progress. The FDA will make those decisions. There are a lot of trials that use MRD as a secondary endpoint to see how it correlates with progression-free survival. And there actually are some trials that have been using it as a cool primary or primary endpoint in the absence of FDA’s decision to accept it. But that is probably going to change in the future. We will see. What have we done in the clinic? Well, we have used it in the same way as we have done with PET-CTs and the regular blood work. So if you use SPEP IFE light chains and you see there is residual disease after you have delivered your planned treatment, people have used what’s called consolidation therapy.

So we have done the same with the MRD test. If there is someone who has a little bit of disease left, we have tried to see if we could make that patient MRD-negative. We have also used it as a tool to build more reassurance. I mentioned before for patients who get this new combination therapies, if they are not very keen on jumping right to chemotherapy with Melphalan and transplant, if they want to collect the cells and keep them in the freezer, using the MRD as a tool to guide for reassurance.

Looking at the randomized trial showing that MRD negativity with or without transplant seems to have the same progression-free survival and in the absence of overall survival, either way, that has been published. But we would always say to patients, there are no definitive studies that have shown that this is how it is. It’s still an area of investigation. So if a patient wants to sort of do everything by the traditional book, we would give every step in the therapy and not pay attention. But a lot of patients say, I would rather monitor, and if I have to do these more toxic therapies, I wouldn’t do it. But I will use MRD to build confidence in myself.

Lisa Hatfield:

Well, thank you so much, Dr. Landgren, these have been great questions, and I actually have another half sheet of questions that we don’t have time for, because that’s all the time that we have. Dr. Landgren, thank you so much, it’s been a pleasure talking with you today. So thank you for joining our Patient Empowerment Network START HERE program. This has been an excellent discussion. Thanks to all of you, for your questions and tuning in. My name is Lisa Hatfield. I’ll see you next time.

Dr. Ola Landgren:

Thank you very much for having me. Thank you.

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Myeloma Patient Expert Q&A: Dr. Ola Landgren Resource Guide en español

March 27, 2024/in MM Newly Diagnosed, MM Programs, MM Resources ND, MM START HERE, MM START HERE Library, Multiple Myeloma /by Kara Rayburn

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Myeloma Patient Expert Q&A: Dr. Ola Landgren Resource Guide

March 25, 2024/in MM Newly Diagnosed, MM Programs, MM Resources ND, MM START HERE, MM START HERE Library, Multiple Myeloma /by Kara Rayburn

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How is Treatment Fitness Determined in Multiple Myeloma?

March 14, 2024/in MM Newly Diagnosed, MM Programs, MM START HERE, MM START HERE Webinar, MM Treatments and Clinical Trials, MM Videos ND, MM Videos TC, Multiple Myeloma /by Kara Rayburn

How is Treatment Fitness Determined in Multiple Myeloma? from Patient Empowerment Network on Vimeo.

How is treatment suitability assessed in myeloma care? Dr. Sikander Ailawadhi, an expert from Mayo Clinic, elaborates on the factors taken into account when determining the appropriateness of treatment for myeloma patients.

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Transcript:

Lisa Hatfield:

Oh, great. Okay. Again, important to see a myeloma specialist to tease out all this information. Thank you. All right. This patient is asking, “I’m 81 and living with comorbidities. The myeloma was diagnosed after bone marrow test. How is treatment fitness determined?” And also a question about that is if you’re given an ECOG status of something you don’t like it, can that be improved after you’ve had treatment?

Dr. Sikander Ailawadhi:

Absolutely.

Lisa Hatfield:

Maybe be eligible for a trial or something.

Dr. Sikander Ailawadhi:

Correct. Correct. That is so important. When this patient mentioned that they’re 81-year-old and they’re living with comorbidities, I think, so when I’m talking to a patient who’s new to me, it’s very important for me to try to tease out what was their performance status or their fitness status prior to myeloma. Because my goal is to try to get them as close to that as possible.

Now if this patient is saying that they were already quite frail before the diagnosis of myeloma and myeloma is added to the frailty, then it becomes a little tricky because we’re starting in a difficult spot. We do determine fitness by asking questions, simple questions like, what can a patient do at baseline? Can they do grocery store or grocery shopping by themselves? Can they walk around the block? Do they get short of breath? Et cetera.

And frankly, there are 81-year-olds who are playing golf every day and are fitter than me. So I’m just saying that age by itself is not the criteria. And, Lisa, like you rightly mentioned, if there are fitness issues coming from the disease itself, then that’s the time that we actually have to work with the treatment, get the treatment started, and then assess the fitness a couple of months later, a couple of cycles later. Because the treatment may have worked and may have improved the fitness quite a bit.

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Navigating Myeloma CAR T-Cell Relapse: Patient Next Steps

March 14, 2024/in MM Newly Diagnosed, MM Programs, MM START HERE, MM START HERE Webinar, MM Treatments and Clinical Trials, MM Videos ND, MM Videos TC, Multiple Myeloma /by Kara Rayburn

Navigating Myeloma CAR T-Cell Relapse: Patient Next Steps from Patient Empowerment Network on Vimeo.

What are next steps for myeloma CAR T-cell patients who experience relapse? Expert Dr. Sikander Ailawadhi from Mayo Clinic explains options for relapsed myeloma patients and shares patient advice.

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Transcript:

Lisa Hatfield:

Okay. So what would be the next steps, Dr. Ailawadhi, for a patient who’s had CAR T and reaches a relapse state or is relapsed?

Dr. Sikander Ailawadhi:

Yep. This is something, unfortunately is the truth of the matter in myeloma at least that we are, we don’t seek cures. We have had some long remissions. I have, for example, patients who are now reaching three, three-and-a-half years of remission on CAR T treatment who received it on clinical trials even before they got FDA-approved.

But, unfortunately, the disease does come back. So what happens is, we are seeing data that the novel, other novel immunotherapies like bispecific antibodies, even the ones who go after the same target as CAR T, BCMA targeting bispecifics, they do have some response rates, good response rates in post CAR T setting. So the bispecific antibodies by themselves may give us 60 to 65 percent response, but in the post CAR T setting, that response might go down to 40, 45 percent. So less responses, but still possible.

There are also bispecific antibodies. There is one available, which is not against BCMA, it is against GPRC5D. That’s a bispecific called talquetamab-tgvs (Talvey). So a novel target. There is…there are of course a lot of clinical trials. There are some clinical trials that are even looking at CAR T post-CAR T. So different kind of a CAR T. Those clinical trials are going out. So what I would suggest is that if your disease progresses after CAR T-cell treatment, you should very strongly consider getting to a specialist myeloma center and get an opinion like you mentioned, Lisa.

That is so important because the choice of treatment is extremely important at that time. And we are trying our best to sequence all the options we have, in a way, actually one of my patients mentioned, one of these days, ”Hey, does that mean that I’m basically buying time till something new and exciting comes along?” And I said, “In a way that is true. That we are trying to stretch all our treatments and get to the point that something new and promising just like CAR T comes, and hopefully we get longer benefits again.”

Lisa Hatfield:

So when you say there’s a possibility of CAR T and then a post-CAR T maybe a second CAR T. Would that be a different target then?

Dr. Sikander Ailawadhi:

So there could be a different target. I have, in fact, I saw a patient who had received one CAR T in a clinical trial and then they were subsequently able to receive a CAR T standard of care, which had been FDA-approved. So they used different CAR Ts, but one was in clinical trials and one was standard of care.

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Myeloma Treatment Timing: Prior Therapies and FDA Approval Rationale

March 14, 2024/in MM Newly Diagnosed, MM Programs, MM START HERE, MM START HERE Webinar, MM Treatments and Clinical Trials, MM Videos ND, MM Videos TC, Multiple Myeloma /by Kara Rayburn

Myeloma Treatment Timing: Prior Therapies and FDA Approval Rationale from Patient Empowerment Network on Vimeo.

What concerns do myeloma patients need to know about CAR T-cell therapy? Expert Dr. Sikander Ailawadhi from Mayo Clinic explains patient qualification for CAR T-cell therapy, including the number and type of prior therapies.

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Transcript:

Lisa Hatfield:

So we have another patient asking, “Do myeloma patients require multiple prior therapies prior to being eligible for CAR T?” And what’s the rationale for not implementing CAR T immediately, which probably has to do with FDA approval based on clinical trials at this point?

Dr. Sikander Ailawadhi:

So any drug, let alone CAR T, any drug can only be given in the situation that it is approved by the FDA. So basically in accordance with that drug’s FDA approval label. Currently, CAR T-cell therapy is approved in the U.S. after at least four prior lines of therapy. And the patient must have had treatment with at least one proteasome inhibitor, for which we have three drugs, bortezomib (Velcade), ixazomib (Ninlaro), and carfilzomib. They must have been treated with at least one prior immunomodulatory drug; lenalidomide (Revlimid), thalidomide (Thalomid), pomalidomide.

And they must have been previously treated by at least one monoclonal antibody, daratumumab (Darzalex) or Isatuximab (Sarclisa). Once the patient has had all these criteria met, they’ve become a candidate for CAR T-cell therapy. Frankly, we cannot just use a drug anywhere because we cannot use a drug where it has not shown to be of benefit. And importantly, it has not shown to be of any risk. So CAR T-cell therapy in the first line setting is being studied in clinical trials, but is not FDA-approved. Currently approved only after four prior lines, but the FDA is reviewing data for both the CAR Ts to see if they may be available sooner. As of right now, that approval is still pending.

Lisa Hatfield:

Okay, thank you. We’re hopeful that that will happen soon.

Dr. Sikander Ailawadhi:

Hopeful.

Lisa Hatfield:

Yeah. So an interesting question from a patient, “Does CAR-T therapy actually change one’s DNA?”

Dr. Sikander Ailawadhi:

No. The CAR T therapy does not change one’s DNA. What happens is, there are T cells taken out of a patient. The DNA of those T cells is modified and then those T cells are given back to the patient. Those T cells do not go and integrate into your other healthy body cells or your stem cells, et cetera. Those T cells, it’s almost like giving a boost of immunity, which is targeted against your myeloma. So those T cells go in and they fill those myeloma cells.

Now we hope that those T cells perpetuate and teach or create some memory T cells and that immunity lasts a little bit longer. But all of that genetic modification stays within the T cells. It does not integrate anywhere else. Now, I know there was a previous question about T-cell lymphomas, that is related to this question in a way because the risk that is theoretical is, that that genetic modification in the T cells might make those T cells replicate uncontrollably leading to a T-cell cancer or T-cell lymphoma. But I’m saying that this is theoretical because while it is possible, it happens extremely rarely and even in the cases where the cancer happened, it has been seen that the cancer may not come from that portion of the DNA that was…that’s where the modification was done. So, low risk.

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What Factors Shape Myeloma Treatment Options After Relapse?

March 14, 2024/in MM Newly Diagnosed, MM Programs, MM START HERE, MM START HERE Webinar, MM Treatments and Clinical Trials, MM Videos ND, MM Videos TC, Multiple Myeloma /by Kara Rayburn

What Factors Shape Myeloma Treatment Options After Relapse? from Patient Empowerment Network on Vimeo.

What myeloma treatment options are there for patients who relapse? Expert Dr. Sikander Ailawadhi from Mayo Clinic explains patient factors that must be considered in treatment options and how treatment options may be impacted.

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Transcript:

Lisa Hatfield:

For those who relapse for the first time, what are the best treatment options?

Dr. Sikander Ailawadhi:

I think that’s a very important, and I can imagine a scary situation. So somebody who relapses in general, not just even the first time, the factors that are taken into account for deciding what treatment they should get, there are broadly three categories of factors. Patient factors deciding what’s the age, what’s the other comorbidities, are they diabetic, are they heart disease, kidney dysfunction, because those things go into the decision of what may or may not be given. So patient factors.

Also importantly, how close are you to your treatment center? Can you come in for infusional or injection drugs time? And again, can you prefer or do you prefer oral drugs only? Et cetera. Those things become important. Then that…so that’s patient factors and disease factors. How fast is the progression? Is it high-risk disease, standard risk disease? Is it biochemical progression like the previous person asked?

Or is it actually a clinical progression in which there’s kidney dysfunction or anemia or bone disease? Because the choices and the urgency of treatment may change. So patient factors, disease factors, and then drug factors are the third class or third category, which is what have you had before? How long have you been on it? Are you on maintenance or not? Is your disease considered refractory to a certain agent, meaning resistant to a certain agent?

Typically, if you were on a treatment and your disease is progressing, that same drug may not be used again. And there are some times that we will reuse a drug, but generally not. We can use the same class, but we may not typically use the same drug. So I think the choice of treatment depends on all of those factors put in. And then we come up with one or two or three regimens and we discuss them with patients. And, of course, being an academic, physician, I must say there is always, you must always seek out good clinical trials if they’re available to you. That is the way our field moves forward.

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What Are Guidelines for Rising Myeloma Marker Levels?

March 14, 2024/in MM Newly Diagnosed, MM Programs, MM START HERE, MM START HERE Webinar, MM Treatments and Clinical Trials, MM Videos ND, MM Videos TC, Multiple Myeloma /by Kara Rayburn

What Are Guidelines for Rising Myeloma Marker Levels? from Patient Empowerment Network on Vimeo.

What are multiple myeloma guidelines for marker levels? Expert Dr. Sikander Ailawadhi from Mayo Clinic discusses marker levels that are checked and levels that could be concerning for disease progression.

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Transcript:

Lisa Hatfield:

This patient is asking, “My M spike keeps rising in spite of chemo. What can I do?”

Dr. Sikander Ailawadhi:

Very important question, Lisa. Every patient must understand what their disease marker is. This patient is asking about the M spike, which is the monoclonal spike, whether it’s in the blood or in the urine. And if the M spike is continuing to increase and there is a significant increase, significant is defined by at least 25 percent from the nadir or from the bottom most point with the, at least an absolute increase of 0.5 gram per deciliter. So half a gram per deciliter. So we want a 25 percent increase, but we also want at least 0.5 gram per deciliter.

So if somebody had an M spike of one at their best point, then the increase to 1.5 is significant. If somebody had the M spike of 0.2, then it’s not the 25 percent increase, it’s the 0.5 that must happen. So they hit 0.7 and that’s a significant increase. So that’s how we think about M spike, 25 percent with an absolute of at least 0.5 gram per deciliter.

If that is indeed happening, this would be considered a biochemical progression. And at that point, it should be considered to switch around the treatment because we don’t want the disease to grow to the point that there are actually symptoms showing up or organ damage happening. We want to be able to capture the disease progression sooner and act upon it.

Lisa Hatfield:

Do you have any recommendations for people who, as we might have some patients watching this, who are light chain only? Any guidelines on if those numbers are rising?

Dr. Sikander Ailawadhi:

That’s an excellent question too. So if somebody has light chains as their marker, we are looking at an increase in the involved serum free light chain. So if somebody has kappa as their marker, the kappa is going up, or if they have lambda as the marker, the lambda is going up. Typically, if both of them go up, that is not disease progression. That could be coming from kidney dysfunction. Somebody is dehydrated and they get labs checked. Both kappa and lambda might be elevated. Again, a 25 percent increase in the absolute. But at the same time, we are also looking at at least 10 milligram per deciliter change. So if somebody had a light chain of two milligram per deciliter, if it goes to 12, that might be a significant change. But I can say that light chains are a little bit more volatile and they do get affected by our fluid status. So if I ever notice a patient with a light chain increase, I’m more likely to repeat the test very soon, maybe even at a couple of days, one week interval, just to make sure that there is a trend rather than just a fluctuating light chain.

Lisa Hatfield:

Okay. Thank you for that information.

Dr. Sikander Ailawadhi:

And I should maybe, very quickly add, we do not check light chains in the urine. Light chains should be checked in the blood. Urine light chains are very nonspecific, and there’s no need to test them.

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Is There a Link Between CAR-T Therapy and T-Cell Malignancies?

March 14, 2024/in MM Newly Diagnosed, MM Programs, MM START HERE, MM START HERE Webinar, MM Treatments and Clinical Trials, MM Videos ND, MM Videos TC, Multiple Myeloma /by Kara Rayburn

Is There a Link Between CAR-T Therapy and T-Cell Malignancies? from Patient Empowerment Network on Vimeo.

What should myeloma patients know about CAR T and T-cell malignancies? Expert Dr. Sikander Ailawadhi from Mayo Clinic discusses the benefits versus risks for myeloma patients who undergo CAR T-cell therapy.

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Transcript:

Lisa Hatfield:

There have been some discussions about post-CAR T, particularly with T-cell malignancies and monitoring for that. Can you just give a little description of that and any concerns that you have with that or any encouragement you have regarding that and whether that weighs into your treatment options that you give to patients when they are asking about CAR T therapy?

Dr. Sikander Ailawadhi:

Absolutely. Extremely important question, Lisa. This really had a lot of discussion going on. It’s been going on for the past few months now. Okay. So first let’s explain the landscape. The FDA reviewed CAR T-cell treatment because of the fact that there were about 19 T-cell malignancies noted in several thousand patients.

Out of those 19 cases of T-cell malignancies, there was one case of multiple myeloma to the best of my knowledge. Now, risk of subsequent cancers is something, unfortunately, every cancer patient lives with, but in myeloma, we have known about that, especially from our historical knowledge of second malignancies with lenalidomide-based (Revlimid) maintenance therapy post-transplant. So subsequent malignancies have always been a risk.

There is some risk that is being talked about with CAR T, but frankly speaking, the way I look at it, the risk is significantly lesser than the potential benefit. Because remember when these CAR T therapies, the two agents got approved in myeloma, they were approved in a situation that there was no standard therapy. And we saw somewhere about 70, 75 percent response rate with one of them and about 98 percent response rate with the other one. So in a setting where there was nothing, you can see the degree of benefit. And the risk of second malignancies is relatively small. So we must discuss this.

A patient must be aware of it, but I think the benefit is way more than the risk. So we document, we discuss, we have specific documentation that we do and specific information that we share with patients, but I think still the benefit is significantly more than the risk.

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How Are Myeloma Survivorship and Treatment Planning Evolving?

March 14, 2024/in MM Newly Diagnosed, MM Programs, MM START HERE, MM START HERE Webinar, MM Treatments and Clinical Trials, MM Videos ND, MM Videos TC, Multiple Myeloma /by Kara Rayburn

How Are Myeloma Survivorship and Treatment Planning Evolving? from Patient Empowerment Network on Vimeo.

How have myeloma treatment planning and survivorship evolved? Expert Dr. Sikander Ailawadhi from Mayo Clinic discusses how patient outlooks have changed and the impact to patient treatment options and doctor-patient communication.

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Transcript:

Lisa Hatfield:

So how is myeloma survivorship evolving, and what’s different now than it was five or 10 years ago in terms of treatment planning?

Dr. Sikander Ailawadhi:

Yeah, I think it’s very important to keep that in mind. When I see a newly diagnosed patient, I’m not just telling them, “Hey, this is your induction therapy, and your transplant is the goal.’ We’re trying our best to decide that patient’s life journey with myeloma over the next 10, 15 and hopefully more years. So we’re trying to pick and choose the regimen that is most likely going to help the patient the most today and most likely will give a longer duration of the response.

So when you say survivorship, that also very importantly brings up the point that patients are living with myeloma longer. We have to manage their health overall. So looking for any side effects from treatment, managing them very well so the patient is able to stay on the treatment and maintain good quality of life.

There are actually, clinical trials looking at stopping treatment when there is a very deep, prolonged response. Again, going towards survivorship and giving the patient’s quality of life. There is looking for other cancers. In fact, I had a patient in the clinic and we were talking about just myeloma in general and I was telling them, “Okay, please remember you may not want to do a colonoscopy, but you already have one myeloma cancer diagnosis.

The risk of subsequent cancers is always there in any cancer patient.” So that was a male person. So I said, “Okay, please do not miss your colonoscopy. Please do not miss your prostate screening and whatever is age-appropriate must be done.” So managing everything because myeloma is not a sprint, it’s a marathon.

We want to make sure that we pace ourselves well so we manage all the symptoms, all the signs. Bone health becomes much, much more important because the same bone structure is now going to carry us longer and many more years. And as you rightly said, planning, which treatment comes first, which comes next, when does CAR T come? It’s not that everybody must get CAR T today. That’s not the answer. So what to use when becomes extremely more important.

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