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Myeloma Research Updates in the Era of Immunotherapy

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Published on December 19, 2019

Key Takeaways

  • There are new clinical trials out including CARTITUDE, KarMMA-1 and GEM-CESAR
  • Doctors are also looking at other combinations of drugs for more combination therapies.
  • MRD and the treatment that follows is still an area of controversy for myeloma experts.

With over 3,000 abstracts, and oral and poster presentations at the 2019 American Society of Hematology (ASH) Annual Meeting & Exposition, what are the important takeaways for multiple myeloma patients? Myeloma Crowd Founder Jennifer Ahlstrom is joined by a panel of leaders in myeloma clinical research to discuss important topics for patients and families living with myeloma. Watch as experts Dr. Larry Anderson, Jr., Dr. Faith Davies and Dr. Nina Shah share the latest news, response rates with novel immunotherapy approaches and what it means for patients making treatment decisions.

This program is sponsored by GSK and Karyopharm. These organizations have no editorial control. It is produced by Patient Power. Patient Power is solely responsible for program content.

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Transcript | Myeloma Research Updates in the Era of Immunotherapy

Jenny Ahlstrom:        

Hello, my name is Jenny Ahlstrom and I’m the founder of Myeloma Crowd, and welcome to Patient Power. Today we have with us three myeloma experts at the ASH hematology 2019 meeting. And we’re really thrilled to have them with us and talk about all the amazing advances that are happening. So, thank you, doctors, for coming.

We have with us Faith Davies from NYU, we have Larry Anderson from UT Southwestern, and we have Nina Shah from University of California in San Francisco, UCSF, and there’s so much to talk about.

I’m a little overwhelmed as a patient, knowing how to prioritize or what sessions to go to. So, we’re going to be talking about a lot of that today and hopefully, we can get your perspective on what’s important and what we should be paying attention to.

So, maybe we want to start with some hot topics. There are a lot of hot topics in what we’re seeing, but maybe we wanna start with some immunotherapy-type topics.

So, Dr. Shah, I know you do a lot of work on CAR-T cell, maybe we want to talk about that. What are you seeing in CAR-T cells, it seems like the initial data came out a few years ago and we’re seeing people respond in really great ways? Maybe not so durable. And now strategies are coming into play as to actually improve the durability. So, what are you seeing in the area of CAR T first?

Dr. Shah:                    

Yeah, I think the responses that we’ve seen are really amazing because a lot of these patients have had five, six, seven lines of treatment. And as you can see from the previous data, from previous meetings, but also here. For example, the CARTITUDE data which was just presented 100 percent response rate so far.

So, nowadays, we think okay, response rate is great. But what we really need to understand is progression free survival. I think I’ve really actually shifted over to wondering about duration of response. Meaning, if you’re a patient and you get a CAR-T cell, and you respond, which you’ll know within a month or two months, how long is that response going to last? Because that ultimately changes your quality of life. Can I go back to work? Can I stop going to the doctor’s office as frequently?

And toxicity-wise, we’ve learned how to manage that. So now with all of this data coming from the patients, I like to look at from how long did it last. And there was just a press release from the KarMMa-1 data, which is the Phase I, so that means many more patients were enrolled and longer follow up and really to understand what the response is. And that showed that in the 450 million dose, which is probably going to be the dose that goes forward, the patients had a median progressing free survival of about 11 months, similar to other data that we saw in the original Phase I.

And it seems weird, 11 months, but it’s important because these are very sick patients. Larry treated a lot of these patients; he was the number one enroller on this trial. And people were really – almost at death’s door. And we don’t want to wait for that long. We don’t want patients to have to search for that. When this gets FDA approved, it’s going to look better because patients aren’t going to be as sick coming to this. 

Dr. Anderson:            

Yeah, exactly. Those patients going into these types of studies may have had only a few months to live without these trials and any other drug in this space might have had a 30 percent response rate and a six-month progression-free survival if they did really, really well. And this is kind of doubling that in a space where the patients have no other options. And I think it’s only going to be showing how well they do when we start to move these closer to the beginning of therapy and earlier lines of therapy, I think we’ll start to see the responses last longer is what the hope is.

Dr. Davies:                 

And we got a bit of a hint of that this morning. Because unfortunately, in China, they don’t have access to quite so many drugs as they do in the U.S. and Europe, but they do have access to CAR-T cells, which is fascinating.

But they presented data this morning of patients who were less treated. And their survival was…

Dr. Shah:                    

Twenty months. PFS 20 months.

Dr. Davies:                 

The time that patients stayed in remission for. 

Jenny Ahlstrom:        

So, you’re almost doubling there. 

Dr. Davies:                 

Yes. So, I think that we’re excited by the data. I think we probably all feel that bringing it up to first relapse or second relapse rather than these very end stage patients.

Jenny Ahlstrom:        

So how do we do that? How do we bring it sooner faster? Because that’s one strategy right, bring it up earlier. Maybe pair it with another CAR T, do a dual CAR T. I don’t know, what are the other strategies?

Dr. Anderson:            

Right now, there are already other trials open looking at second lien and third line CAR T-cell therapy. Also, studies looking at combining, I think one of the abstracts this evening will be dual targeted CAR-T cells, CD38 plus BCMA directed. So, we’ll see what the final results of that look like.

But yeah, studies are already initiated to look at second- and third-line therapy with the KarMMa-2 and the KarMMa-3. And then early this next year, we’ll be hoping to open even first line for high-risk chromosome patients.

Jenny Ahlstrom:        

Great. That’s amazing. That’s something—I know the challenge in getting into the CAR T has given patients just sense of nervousness. And now some of these other immunotherapies are targeting the same things. Like the BiTES or the antibody drug conjugates. And we don’ know if they’ll work as well as CAR T, they seem to have really good response rates themselves. So, do you want to address the BiTES, the bispecific antibodies. And we just did something and saw how many are being developed. I don’t know the exact number, but maybe you do.

Dr. Davies:                 

As you mentioned in the introduction, it’s overwhelming for patients, it’s actually overwhelming for doctors as well. Because we’re really excited, but we’ve got now probably three approaches of different immunotherapies to use. And in each approach, so the CAR-T cells. The bispecific, which are I guess antibodies where they grab the myeloma cell with one hand and they grab an immune cell, a T cell with the other hand and bring them both together so that the myeloma cell can get killed off. And then we have the antibodies themselves, just plain antibodies.

And the question we’re all asking, I think it’s the main question the doctors are asking at ASH, which patients do we offer which treatment to? Because these bispecific are what they call off the shelf. So rather than having to undergo an apheresis to collect your cells, these are potentially, we can take something and give it from the pharmacy.

 And the response rates look very good. We’re still waiting for some of the data, again, as Dr. Shah was saying as to how long they last. But again, it’s looking really interesting. And I don’t think we truthfully know which is the best approach. And we’re all going to be watching really closely as to—and it may be there isn’t a winner, which is great. It maybe it depends a little bit about the type of myeloma you have, how aggressive it is. Because as you mentioned, some patients can’t get into a T-cell study, because their myeloma is progressing very quickly, and they can’t make the CAR-T cell. Or it may just depend on patient preference, whether the patients would prefer to have an infusion or the CAR-T cell. What do you think?

Dr. Anderson:            

Yeah, I think some of it will be depending on patient characteristics. If they have rapidly dividing myeloma, they can’t wait a month for those CAR-T cells to be produced. And so, they will have to have something off the shelf targeting BCMA. So that might be the population where the BiTES or the ADCs would be a lot easier and better. Whereas patients getting CART usually have to be fit enough to travel to academic medical centers, to bone marrow transplant units. It comes with a lot of times, in patient stay and some risks with that. So, I think some of that will come down to how frail the patient is.

 For example, the antibody drug congregates may have less risk of cytokine release syndrome and neurotoxicity. So those patients who are frailer may benefit more from the less toxic versions of the therapy, even though they’re all targeting the same target. And the other question is even if one may or may not be better than the other, how can we sequence them? Can a patient respond to one and then respond to another even if it’s targeting the same receptor, like B-cell maturation antigen, or will we need to find something different for those patients. So those studies will be critical to know if we can still respond to the same targeted therapy with a different mechanism.

Jenny Ahlstrom:        

And as you help answer, I’d like to know also about the status of your T cells. So, let’s say I’m a patient who’s been through lots of lines of therapy. My T cells may not be as strong as they were at the beginning. Or with myeloma is it just already depressed anyway, because let’s say that I have newly diagnosed myeloma. Where does that all factor in? Because I can see some of these approaches being off the shelf, or what they call allo, somebody else’s T cells are being used to develop these. So, what’s the opinion?

Dr. Shah:                    

Yeah, this was actually recently published by our colleague, Dr. Al Garfall regarding T-cell health. And he was able to show that patients with newly diagnosed myeloma, if you look at their T cells, are healthier than those with relapsed myeloma. And with the ones that are relapsed, the patients with healthier T cells have better outcomes, for example with CAR-T cell.

And actually, the University of Pennsylvania group has done a great job of trying to profile the T cells. So, what does this mean for patients? It means that if these get approved, I shouldn’t wait – like we were talking about, until the last minute. But in the case that you have to wait, as you mentioned, there are allo T-cell products being developed.

So, there are at least three or four being developed right now, and they’re in clinical trials. The advantage of them, as Larry mentioned, you don’t have to wait those four weeks for the T cells to be manufactured. For example, with the autologous product, it takes about four weeks, five weeks. You can actually say, hey, my patient needs this. Can I call and get this cell product delivered to the hospital next week, and this might be possible.

The challenge is that these are allo T cells, right, so your body’s gonna reject them or they’re going to reject you. So, there are different technologies to tell the T cells, hey, don’t attack the patient’s body. And there are also technologies to help the patient say hey, don’t attack the T cells. Let them do their work.

So that’s what science is happening now. Because we want to get something that’s easy, off the shelf, don’t have to wait, and doable and patients can have access to.

Jenny Ahlstrom:        

So, in terms of a patient strategy, if someone’s relapsing and they’re seeing all this amazing stuff happening at ASH, and it still seems like it’s really early. So, as a patient, I am thinking maybe I should jump into one of these because it looks so promising, and my T cells are healthier. But maybe you’re still in the Phase I, where you’re still testing the dose. And maybe I’m not going to get the highest dose, but maybe I am. It’s hard to decide as a patient what to do. Do you have any thoughts on how to…?

Dr. Anderson:            

…some of it comes down to if there’s a slot on the trial that’s available at that time or not. And even if you wanted to give that patient something, you might not be able to if there are no slots available at that time.

Dr. Davies:                 

I was going to say, as a patient, I think one of the important things is to use many of the tools that are available on the web about trying to figure out where would be the nearest center I might be able to get my CAR-T cells from. Or where are the other centers that are close to me that are doing some of these clinical trials. Because as you say, at the moment, none of them are available or FDA-approved, so they’re all clinical trials. And as Patient Power always says, knowledge is power and making sure you know where your nearest center is and getting connected with them is really important.

Because in an ideal world, it would be really very quick of going through this process of hey saying, right, okay. I’ve relapsed. I need the treatment; I’ll go here next week and get enrolled. But often, it’s actually quite useful to be on the center’s radar and for the center to know about you. So that if and when you may need that therapy, then those introductions will have been already done.

Jenny Ahlstrom:        

That’s an important point. At the Myeloma Crowd, we built a tool called HealthTree, it’s an online tool that helps patients find treatment options. But we also partner with SparkCures to find all the clinical trials. So, you have a great point, because sometimes your center doesn’t have a particular study open that you might want to consider. So, you can enter in information and pass us even your labs, to make sure you’re actually eligible for that.

 So, there are 450 open myeloma studies right now, and that helps you get your list down to about 10, 20, if you haven’t had a lot of prior therapy, maybe 30. That’s still better than 450. So navigating is an important point. To contact your center or other centers where these studies are happening and either go get a consult or talk to the recruitment team about the status of the study to figure that out in advance.

Dr. Anderson:            

And if there’s a particular type of therapy that a patient really would like to get, they may have to look into going to other states even to find a clinical trial that’s available. For example, at our site in Texas, we had patients that came from Minnesota and Michigan to get a slot on a trial because theirs were all full. So, there are online resources for finding clinical trials and which sites are available. Also, Facebook groups for immunotherapy and CAR T-cell therapy for myeloma can help direct and other patients can have advice on where they went and what their experiences were.

Dr. Shah:                    

And we even talk to each other. Like we’ll say, hey, do you have a slot? And we try to advocate for the patients as well. So, I really agree with this knowledge is power for all of us involved in the patient’s care.

Jenny Ahlstrom:        

Yeah, I agree. Well, let’s talk about other aspects too, of what’s happening at ASH, because there are a lot more even outside of the immunotherapy realm. We’re looking at other approaches. So, there’s a lot going on also in the CD38 category with daratumumab (Darzalex) and isatuximab is getting closer to approval. And a new Takeda drug is being developed going after this same CD38 target.

So sometimes people are talking about using daratumumab or those types of drugs as maintenance therapy, which we haven’t really heard before. And new combinations, like the CANDOR study that’s combining carfilzomib (Kyprolis)—that’s a whole different topic.

Dr. Shah:                    

Yeah, I think daratumumab has had this whole evolution. Four years ago, it was just something you used as the last thing, and now it’s developed so rapidly. So now, and then it was the first relapse we’d use it, now it’s we use it up front. So, there are four trials looking at daratumumab up front and all of those, thus far, have been positive.

Although the GRIFFIN study, which is going to published at this meeting also, is not positive from progression-free survival yet. It’s positive from depth of response.

So, what’s happening is we’re gonna start using daratumumab more in the front-line setting and then the question will be maintenance. And there are a couple of trials looking at that. There’s one with the Southwestern Oncology Cooperative Group, SWOG. And there’s another trial, where if you’re MRD-positive after transplant, you can be randomized to get lenalidomide (Revlimid) or lenalidomide and daratumumab. And the end point is MRD, which I think is actually a cool end point, trying to see if we can get patients into MRD negativity as a surrogate really, for survival, because we know it does correlate.

So, I think daratumumab is gonna move to be part of our sort of natural frontline, potentially maintenance therapy, and then it’ll be what next.

Dr. Anderson:            

And do we need to stay on it indefinitely? Should we stop it at two years? Those are other questions with daratumumab maintenance as well.

Dr. Davies:                 

And it’s been—I guess it’s two things I want to say. First one is around daratumumab. And from a patient perspective, just being really careful around infections, because we do know that patients can sometimes get some unusual infections, so coughs and chest infections and so on, particularly when patients have been having it for a wee while, so that was one thing.

But also, there’s been other information at this meeting about maybe using proteasome inhibitors as maintenance, so ixazomib (Ninlaro) with maintenance. And then obviously, we all know the data of lenalidomide (Revlimid) at maintenance. And so, we now have a choice of different potential maintenance therapies. Some of them are not approved by the FDA for maintenance yet, but there’s evidence there to suggest they’re going to be beneficial.

And again, we always come down to which is the best option for patients. And I think we’re in the same situation. I’m not sure at the moment we know which is the best option, however we have three very good options. And it may be, in the long run, as Dr. Shah said, the best option is actually putting two of them together, two of those things, so.

Jenny Ahlstrom:

Right. And when you have a monoclonal antibody maybe and you’re adding that to maintenance, maybe there’s not a lot of that extra side effect to it, so you can do that. Or for high-risk patients, maybe you should be using that proteasome inhibitor or…?

Dr. Anderson:            

…yeah, high-risk, we routinely use a proteasome inhibitor plus an  maintenance. I’m not sure what you guys are doing.

Dr. Shah:                    

Yeah, we do. We give consolidation after transplant and use a modified version of that for maintenance.

Jenny Ahlstrom:        

And let’s talk a little bit, because you mentioned MRD, or minimal residual disease testing, and how that’s kind of evolving. We were at a session last night where we were talking about MRD, and what’s the general consensus?

I think the big goal for patients is kind of just to know what’s happening with your disease. But from a research standpoint, patients are living so much longer now that MRD could maybe help make research go a little faster. Do you all want to talk about that?

Dr. Shah:                    

Yeah. This is probably one of the most controversial areas in myeloma. And I call MRD the Goldilocks end point, because getting overall response rate particularly in these immunotherapies, etc. trials is too short. It’s not enough. And then waiting for progression free survival is too long. We just don’t have time to do that, and patients want to know. So MRDs like the Goldilocks end point to know what to do.

nd really, kudos to many of my colleagues who’ve asked the FDA to use these as an end point. The thing is, once you know your status, it’s hard to know what to tell the patients. So, I always say, MRD is like wedding china, it’s like great to have, but you don’t know what to do with it.

Because when the patients are MRD-positive, let’s say after transplant, I don’t know what to tell them about what to do next. I don’t want to say you won’t get maintenance because you will. And even if they were MRD-negative, I would still do maintenance. But what are you telling your patients? 

Dr. Anderson:            

Yeah, I mean, we say that that’s a good prognostic marker. That those patients in your group do better. But I don’t think we have any data that suggests that we should not do maintenance at this point, until trials show us further information. Certainly, if you’re MRD-positive, should we add something or do something different? We don’t really have that information yet either.

Dr. Davies:                 

So, I’m maybe a little bit more upbeat about it. And so, it really highlights what Dr. Shah was saying about there being controversy. Because I think there’s always an argument whether MRD is ready for prime time. I would argue, say my patient has had a transplant and is MRD positive, okay. We know—and maybe high-risk. We know that patients who are high-risk and MRD-positive, don’t do so well.

And so, I would argue, in those patients, I want to do something different. I want to make sure that they are having the best treatment I can give them at that time point. And so, I’m going to be—I wouldn’t say aggressive, but make sure I’m really optimizing that therapy for that patient.

The other area I think it’s really very useful at the moment is maybe for a patient who’s been on maintenance for some time, let’s say two years, and is struggling with side-effects. And the maintenance is now actually impairing their quality of life rather than improving.

If I knew they were MRD-negative, it would help my conversation with them, okay. I appreciate that I don’t have any definitive evidence to support either of those arguments, but I do think they’re useful.

On the Twittersphere, and Dr. Shah’s a huge tweeter, the abstract that was voted the best abstract amongst the myeloma doctors this year, was actually one trying to use MRD to help direct therapy. Which is where we all want to go, okay.

And so, patients where they had their MRD test measured, they had to have two tests that were negative. And then if they were negative, their therapy was adapted too.

And we don’t have any results of that approach, but the actual fact that people were trying that, and it was shown to be a feasible approach, I think everybody is really excited about it.

Jenny Ahlstrom:        

And maybe for patients who are just starting to relapse, using MRD to watch the pattern of relapse might be helpful over certain time points. Like how fast this is going, might be helpful, I don’t know.

Dr. Shah:                    

Yeah, it’s hard because you can get bone marrows, and you’ll see a person who’s MRD-negative and then maybe another bone marrow eight months later, whatever you chose, is now showing MRD-positive. It’s hard to make clinical decisions on that, and yet you want to because you know what that means. It’s just that we don’t have clinical trials that have shown us what to do then.

So, it really is a conversation—every patient is not a data point, they’re a patient, they’re a person. And so, you have to have that conversation.

Dr. Anderson:            

And I think another key with MRD testing is that it’s not just a one snapshot in time. You need serial measurements to know how stabile that MRD negativity is. And just because they’re MRD-negative right before transplant or right after transplant is not the same as MRD negative for two years, period, after their transplant. 

Jenny Ahlstrom:        

So, if you’re seeing multi-year MRD negativity following treatment, maybe you can have a little more confidence, like you were saying. Yeah, that makes a lot of sense. 

Dr. Shah:                    

Yeah, we actually looked at this. And serial MRD negativity for patients who were either serial negative or decreasing over time, did far better for progression-free survival than patients who were serially positive.

Jenny Ahlstrom:        

And as we’re talking about diagnostics, the testing seems to be getting better to detect—I mean, MRD is trying to test this lower level of disease. But other new tests like the mass spectrometry test, can you talk a little bit about that? Or liquid biopsies. 

Dr. Shah:                    

That was actually presented today. I don’t know if you guys saw that, but they looked at mass spec in the context of the GEM-CESAR trial, which was a high-risk, smoldering myeloma trial. So, it was kind of like an extra thing going on with the trial, where they compared the mass spec of the blood—now this is the blood versus the serum immunofixation S-PEP or common M protein we look for, versus the flow-based MRD testing. So not the genetic, but the flow based from the bone marrow.

And they were able to show, certainly in comparison with the S-PEP, that this mass spec technology was more sensitive at detecting progression or detecting the presence of disease. And it was at lest as sensitive, if not better than the flow. So, what does that mean for a patient?

Because if this turns out to be true, we’re not gonna have to do all these serial bone marrow biopsies that they hate, and we hate. We don’t want to subject patients to this and it would be better if we could just use this technology.

And I’m really hoping, I really, really hope, in the next 10 years, we’re going to get this circulated tumor cells, cell-free DNA, all of these things that have been being worked on so that we can eliminate bone marrow biopsies, because I just hate doing them. I don’t do them even, but I hate having to put my patients through them.

Dr. Anderson:            

Yeah, I think part of the reason they’re finding that the blood testing may be better is because if you just do a random bone marrow biopsy in the iliac crest, you may be missing what’s going on throughout the rest of the skeleton. It’s just that the myeloma can be patchy in many cases, especially in relapsed disease. And so, if you’re doing something blood based, you’re going to catch the product from all over the body. Whether that’s with the mass spec or mass fix of the blood, or hopefully in the future cell-free DNA that’s coming loose from the myeloma cells throughout the patient’s body.

Jenny Ahlstrom:        

And how long do you think it will take to roll mass spec out to lots of different facilities? And does it work for non-secretory myeloma? 

Dr. Shah:                    

That’s a great question.

Dr. Davies:                 

Yeah, so as far as rolling it out. All tests have to go through a kind of quality control process and be approved by the FDA. In some cases, there’s actually a relatively easier one to roll out because many hospitals already have a mass spec machine. 

Jenny Ahlstrom:        

Oh okay.

Dr. Davies:                 

So they just have to buy the kits to do it and we’ll be able to run it like that. The kits still have a process to go through. I think it will still be a couple of years.

Jenny Ahlstrom:        

And how many facilities are doing it right now?

Dr. Davies:                 

So, in the U.S., many of the big myeloma academic centers are doing it. They have slightly different tests. There’s also a company that’s producing a kit as well.

Dr. Anderson:            

And to answer your other question, it probably wouldn’t really help if there non-secretory, because there’s really no marker in the blood.

Jenny Ahlstrom:        

Right, so you’re still not picking up the M protein?

Dr. Anderson:            

Unless what we though was non-secretory, maybe they’re just minimally secretory and there may be a small percentage of patients where it can pick that up. If they’re completely non-secretory it wouldn’t work.

Dr. Shah:                    

That’s why I’m really excited about the DNA, because that’s the fruit, right? The cell. You know, all these proteins are just the petals on the flower, right? You want to find the flower. So, I think this DNA approach will be really cool and I’m not smart enough to develop it but someone else is. And I really hope that we can do that soon.

Jenny Ahlstrom:        

Well let’s talk also about other strategies for relapsed patients, and then if we have time we’ll go up earlier. What other strategies are you seeing outside of immunotherapy approach? Whether it’s combinations or new drugs like selinexor (Xpovio) or venetoclax (Venclexta), or things like that.

Dr. Davies:                 

So I think at this year’s meeting there’s been some really great abstracts about selinexor showing that in the relapsed and refractory setting that it is able to produce good responses and that you can combine it with other drugs such as pomalidomide (Pomalyst). And that’s a nice oral combination, so I think that’ really good.

There’s also some very, very encouraging data about venetoclax. Venetoclax has had a little bit of a bumpy ride and the researchers have gone back and looked at all the data and presented much of it here, and have really shown that if myeloma patients have a particular myeloma chromosomal abnormality, the t(11;14), that the venetoclax seems to be extremely effective in that group.

But also in another group of patients that have one of the proteins that controls myeloma and cell death. If one of those proteins is very high, called Bcl-2, those patients seem to benefit from it as well. And so, I think that the hope moving forward if we can really identify which patients benefit that most from it, that we can not only get the best response rates and the best duration of response, but we can also hopefully minimize the side effects. Those two drugs have actually been very prominent at this meeting, and I think they’re both drugs which may be a little more accessible to patients today, rather than talking about things that are in clinical trials or a little bit further away.

Jenny Ahlstrom:        

Any other thoughts on strategies for relapsed that people should consider? We attended one session that was talking about, what do you do for relapsed refractory myeloma? And it was almost like, well you should do a clinical trial. Like we’re still combining and we’re still trying to optimize the combinations. 

Dr. Anderson:            

I think that’s key, is just if you don’t have access to a clinical trial. Optimizing your combinations. A lot of times, we’ll end up doing four drugs that are combined in these patients that have failed everything. And then we can still get responses to these drugs in combination that they had failed separately before. So that’s key to remember.

And sometimes a year or more of remissions from just adding Cytoxan for example, to your antibody and IMiD combo, things like that can really get you some mileage to get you along further until one of the trials opens up.

Dr. Shah:                    

I was going to say, I know this might be also controversial, but I’ve also done second transplants. Because sometimes people have had a couple years of duration. And I’m a person that loves it when a patient doesn’t have to come back to see me as frequently, for example, for serial infusions or whatever. And it’s kind of a nice way to get people into remission. Understanding that it’s not going to be as long as the first one. And they can go on maintenance therapy and sort of go back to life a little bit. So that’s not a bad option and that’s why we try to collect enough stem cells up front to do that.

Dr. Davies:                 

There was one other abstract and two other things we believe, or we hope are about to happen in the myeloma world. So, there was an update of the experience of isatuximab, which we’ve already talked about with pomalidomide and dexamethasone in the relapse and refractory setting. And we’re hoping that that data is going to be presented to the FDA shortly and approved.

And the other drug that is in that space as well, but wasn’t presented at this meeting, but we believe is in that kind of – hopefully in the FDA’s hands at the moment, is the BCMA antibody from GSK. And so, both of them again are drugs—those are at least four drugs that the myeloma patients that may not have received before, which could be put with other combinations, which are already approved or very, very close to being approved. 

Dr. Shah:                    

And community friendly. Like the BCMA ADC, which is antibody, drug conjugate, is something that is going to be community friendly, so you don’t have to go to a big center, necessarily to do that. And I think that’s gonna add more choice for the patients. Ultimately, we want patients to feel like they got the drug that was the right fit for them.

Jenny Ahlstrom:        

And their life circumstance, too. Like sometimes it’s how much do you have to travel. And sometimes with the transplant versus other things, as a patient I kind of feel like you’re going to get the medication either up front or all in one or over time, so you’re going to get it. And sometimes transplant will get you out multiple years. And sometimes it’s a better strategy if somebody is trying to work full-time and has a very demanding job.

The nice thing, and what I’m totally blown away with in this meeting, is just the amount of development that’s happening in myeloma. 

Dr. Davies:                 

I was going to say, I’ve been doing myeloma for 25 years now. And I think when I first started, we didn’t really have any choice. It was like, this is what we’ve got. I’m really sorry.

And now, it’s really interesting, because the question is each patient is different. We know each patient is different. And we may not be at the position of being able to say this is definitely what you should receive. But we can often say this is what you shouldn’t have. These are therefore your remaining choices. Which one for a physician’s perspective do we think might be the best fit? And which one from the patient’s perspective do we think is the best fit?

And it’s really an amazing position to be in. 

Dr. Shah:                    

That’s why I call myself a my-llennial. Because we didn’t have all these things before. And it’s true and I even wrote this piece about it in the JOP. You always hear my older colleagues by like, oh, well back in the day, we only had—and it’s like, oh, then you walked up the hill both ways. But it’s true. It really is true.

And it’s just exciting and it’s a journey with patients and we really like to engage about that.

Dr. Anderson:            

And you know, other things to help answer that question or to more individualize or personalize therapy are trials like the my drug trial that we have going on right now, that really seeks to determine if specific mutations make that patient benefit from certain drugs that target that mutation. And just really help to personalize therapy for these patients.

Jenny Ahlstrom:        

Good point. I think we have a few minutes left, so let’s talk about smoldering myeloma for a minute. I’ve heard a lot about smoldering myeloma. Like should we get rid of it as a category? Should it just be MGUS and myeloma. Do we keep it as a category? Do we treat? Do we not treat? Like half the cases might not even be a smoldering myeloma. They might be active myeloma.

So what strategies are you seeing for this group? Because myeloma is a mind game. As a patient, you play that game all the time. And it would be easier for patients if we had a go-to strategy that seemed to be effective. But you don’t want to overtreat, you don’t want to undertreat. It’s really tricky. Thoughts on that.

Dr. Davies:                 

Look at the enthusiasm to answer that question.

Dr. Anderson:            

I think it’s really controversial right now. There’s certainly data that at least a certain subgroup of patients may benefit—certainly will benefit from treatment. Especially the higher risk patients that have higher m-protein and higher plasma cells and higher light chains. Those, you could argue that there’s data that those patients would benefit from treatment. Every risk feature doesn’t mean that they—just because they have one risk features doesn’t necessarily mean they’ll benefit from this.

And we’ve got many patients that have had smoldering myeloma for over 20 years and haven’t needed treatment. So, we really just want to protect those patients and not necessarily expose them to side effects that they may not need. And perhaps, maybe even getting them on therapy that might make them resistant many years before they needed the therapy.

So, right now, we’re not really treating everyone with high-risk smoldering, unless there’s a clinical trial. Certainly, the ultra-high risk with many of the risk factors, we’re certainly considering it through.

Dr. Shah:                    

It’s really patient dependent. Sometimes patients come and say I want to be treated, and I have to convince them, no, you don’t need treatment. And others are like please don’t tell me that I need treatment, because I want to go play tennis, and I want to have my life, and I don’t want to be a patient. I think it’s really important to keep on top of smoldering patients. I really—even if I have to do remote access. I look at their labs, they’ll come to my inbox. I can actually do tele visits with them. Whatever I have to do, because I don’t want to miss anything.

And if that’s okay, then I’m okay watching them. But the people in the smoldering space have done an amazing job of trying to get people on clinical trials. I think immunotherapy, vaccine therapy, their T cells are actually really much better in that state. That’s a great place for that.

So, I really hope we’ll have more research to answer these questions. We don’t know the answer. It’s hard to tell a patient I don’t know, you know.

Dr. Davies:                 

There was a debate on Friday about it. And the panel and the room split. But I think what one thing everybody did agree on was that  there’s a group of smoldering myeloma patients who are the high-risk smoldering—well, are the ultra-high-risk smoldering myeloma patients. Who as you say, probably should actually be considered as myeloma?

There’s then a group of smoldering myeloma patients who are low-risk and should just be monitored closely. So, the actual group in the middle is relatively small, okay, which are the controversial group. And certainly, in my own practice, for that controversial group, I want to not only see them when I first meet them, but see them again maybe one month, two months, or three months later and repeat many of those tests again.

Because I think the definition of smoldering means you’re stable. I think if you’re moving up, then that puts you into a different box. It doesn’t mean that we need to start treatment differently, but it puts you into a different box. So, I think the real controversy is over the ones that are very stable, and what we should do about that. 

Jenny Ahlstrom:        

Yeah. This is like a repeating theme that I tell patients all the time that are with us, with the foundation, and in the meetings, we go to and everything, is you have to have a myeloma specialist in your corner. I mean, it’s so clear to me how that needs to happen. And there’s a finite number of you, but you’re so amazing at what you do that we need to get your expertise out to the community practices as well because 80 percent of myeloma patients are being seen there.

And we tell patients all the time, consult with a myeloma specialist, especially if your numbers are going up, if you’re newly diagnosed, if you’re smoldering myeloma, if you’re relapsed, please go, and consult with these people. Because they are so knowledgeable about this disease.

And like you said, if you’re running these tests at one, two, and three months, then it can all make sense for them. They know what to watch for.

Dr. Davies:                 

Our community colleagues are amazing, and they have such a high knowledge level and they treat many, many different kinds of cancers, okay. I don’t have their knowledge level. It sounds dreadful. Don’t come to me if you have breast cancer. That would be a really bad mistake, okay. However, the in-depth knowledge that your myeloma physician has on myeloma is really important.

And for me, personally, the model of care, I always encourage patients is to have their great local oncologist, and then a myeloma physician. And there’s a three-way conversation. 

Dr. Shah:                    

Yeah, I totally agree with that.

Dr. Anderson:            

Yeah, just because they come to see us for a second opinion, doesn’t mean they have to travel to get their treatment. We can make recommendations, and then they can usually get that with their local oncologist.

Jenny Ahlstrom:        

Well, I totally agree with that strategy. So, are there any other thoughts that you have that really stand out to you from this conference? 

Dr. Anderson:            

I think it’s the era of immunotherapy. 

Dr. Shah:                    

Clinical trials. A lot of good clinical trails out there, and information. There’s so much information. Thankfully, because of groups like yours and these types of productions now, patients have access to it. It’s so, so important for people to feel in control in some part of their disease.

Jenny Ahlstrom:        

And to me, it feels like we need faster data aggregation so the results can read out in a faster way. So, having patients aggregate that data and share it back with you is really key.

And I don’t know, you just have to—my husband’s from the startup world so we lived in that world for over 25 years, and it’s fail fast and fail early, so that’s the secret to success because not everything will work, right. And some of these things that are in clinical trial development may not be the ultimate at the end. But the faster you know, the faster you can weigh in on the things that are working and start using them in the clinic sooner and get them FDA-approved sooner.

Dr. Davies:                 

Yeah, and just on that note, it’s really quite interesting watching how the myeloma world is evolving to embrace those kinds of ideas. So, as you say, from a physician perspective and a pharma perspective, that idea of trying to get results as quickly as possible, redesigning how we do clinical trials so that we don’t do—we try to do things in parallel rather than in series.

But also, then, how having the patients involved in the whole discussion as well. Making sure that we result in patient friendly regimes. And there has been a huge change in it, and it’s for the good, it’s for the best.

Dr. Shah:                    

Yeah. Quality of life endpoints, even in the CAR-T trials, things like that.

Dr. Anderson:            

And like Nina said earlier, the earlier readouts like the MRD negativity can really help speed things up as well.

Jenny Ahlstrom:        

Well, patients want to help you. And the work that you’re doing is truly stunning. And if patients can weigh in by using tools like health tree or SparkCures or other things like that to help you come to conclusions faster, that’s where we all want to be. We want to donate the samples, and we want to join the studies, and we want to get you where you need to be.

Dr. Davies:                 

Just on a closing note, one of the things we didn’t cover was exactly how much what we call real-world data was presented at this meeting. Which is there’s always this concern that the data from a clinical trial, doesn’t really reflect the patients we see on an everyday basis. And there’s so much data collected from various databases showing which drugs actually do more forward and reflect what we’re doing in the clinic, compared to where they maybe don’t match up with the clinical trial.

And that’s so important for patient’s knowledge, physician knowledge, but also for their healthcare payer’s knowledge too.

Dr. Anderson:            

And I think two of the underrepresented patients of myeloma patients are some of the most common, the minorities and the frail older patients, and most of those patients aren’t represented in these trials. And so, there’s a big push right now to have trials specifically, or at least try to encourage those patients to get involved in clinical trials.

Jenny Ahlstrom:        

Well, thank you for empowering patients with the information that they need to make sense of all of this development. It’s a huge blessing in myeloma to have all of this happening. And it’s a huge blessing as patients to have all of you doing this work. So, we thank you and we thank you for watching Patient Power.

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

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