Tag Archive for: ciltacabtagene autoleucel

Current and Emerging CAR T-Cell Therapies for Myeloma

What are the current and emerging CAR T-cell therapies for myeloma? Nurse practitioner Donna Catamero discusses approved CAR T-cell therapies for multiple myeloma, who they’re appropriate for, ongoing research to expand their use, and treatment options if the disease returns after CAR T-cell therapy.

Donna Catamero is a Nurse Practitioner and associate director of the Multiple Myeloma Clinical Research Program at Mount Sinai Hospital in New York City. Learn more about Donna Catamero.

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Transcript:

Katherine Banwell:

Donna, welcome. Thank you so much for joining us. Would you please introduce yourself and tell us about your role at Mount Sinai? 

Donna Catamero:

Sure. I’m Donna Catamero, I’m a nurse practitioner, and I’m the associate director of the Multiple Myeloma Clinical Research Program at Mount Sinai Hospital in New York City. 

Katherine Banwell:

Would you tell us about the currently approved CAR T-cell therapies and which myeloma patients they may be right for?  

Donna Catamero:

So, currently, we have two products available for patients. The first is idecabtagene vicleucel (Abecma), and it’s approved for patients with relapsed/refractory disease who have received two prior lines of therapy, and this includes exposure to an immunomodulatory agent, so, your lenalidomide (Revlimid), your pomalidomide (Pomalyst), a proteasome inhibitor, and that includes Velcade/Kyprolis, and an anti-CD38 monoclonal antibody, so this is your daratumumab (Darzalex) or isatuximab-irfc (Sarclisa). 

The second product we have to offer patients is ciltacabtagene autoleucel (Carvykti), and this is approved for patients a little bit earlier on, so, also relapsed/refractory disease who have received at least one prior line of therapy, and it must have included proteasome inhibitor and an immunomodulatory agent, and they need to be refractory to Revlimid. So, what “refractory” means is they relapsed while taking the Revlimid.  

And both these therapies are important for patients, so if patients are inquiring about CAR T therapy, they should ask their providers what product is available for that. 

Katherine Banwell:

Let’s talk about research in CAR T-cell therapy. What new options are being studied, and how far along is the research? 

Donna Catamero:

So, we’re actually very excited. So, the two products, Abecma and Carvykti, we’re actually looking at them in newly diagnosed myeloma patients, and this is regardless of if patients are eligible for transplant or not, and we’re looking at comparing transplant versus CAR T therapies, so we’re hoping to move CAR T therapies for newly diagnosed – so, first-line therapy – so this is very exciting, and we’re also investigating new products with dual targets. 

So, right now, our two approved CAR Ts, they target BCMA, so now we’re looking at CAR Ts that are targeting BCMA and another target – so, GPRC5D or CD19 – so this means that the CAR T is grabbing onto more cells, so, in theory, it would have a higher cell kill.  

And then, we’re also investigating CAR Ts that we call off-the-shelf, so, autologous CAR Ts, so, donor CAR Ts, and this is actually exciting for patients who maybe can’t wait for manufacturing of their T cells, and now we can use donor T cells. So, these are earlier on studies, so we’re hoping within the next few years, more options will be available for patients.  

Katherine Banwell:

Yeah. What happens if the myeloma comes back after T-cell therapy? What are the treatment options available beyond CAR T? 

Donna Catamero:

Earlier on, we were hoping that CAR T would be our cure, but patients are getting very long, durable remissions from their CAR T therapy. We see patients who are five, seven, eight years out from their CAR T therapy, so patients do have a long time in remission, but the myeloma can come back. 

And what do we do with these patients? We actually have been very successful managing patients post a CAR T relapse, so we are looking at bispecific antibodies, which were recently approved over the past several years, and we see patients who have had relapses from their CAR T go back into a remission with these bispecific therapies, and again have long, durable remissions. So, we can absolutely manage patients if their myeloma comes back after CAR T therapy. 

What CAR T Research Is Ongoing to Improve Treatment Response?

What CAR T Research Is Ongoing to Improve Treatment Response? from Patient Empowerment Network on Vimeo.

 How can CAR T treatment response be improved with research? Expert Dr. Krina Patel from The University of Texas MD Anderson Cancer Center discusses the CARTITUDE, KARMMA-9, and LEGEND studies and proactive patient advice about bispecific therapy and CAR T.

[ACT[IVATION TIP

“…before you start bispecific therapy, talk to your doctor about CAR T. And the reason I say that is that when you get a bispecific therapy, and currently that is not a fixed duration therapy, it is a continuous therapy. So patients are on it until they relapse. And the problem is that once you relapse on that T-cell therapy, your risk of losing BCMA, losing the antigen is much higher. There are mutations that we’re seeing that most patients get.”

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Transcript:

Lisa Hatfield:

So, Dr. Patel, given the risk of relapse following initial CAR T therapy, what approaches are being investigated to enhance the persistence and durability of CAR T-cell responses in patients? I know there are a lot of theories out there saying things like antigen loss might be an issue, the loss of the target BCMA, T-cell exhaustion, the environment of the bone marrow, what of those theories are being investigated or looked at?

Dr. Krina Patel:

Yeah, I think without causing too many issues with why we think CAR T is so great, where it’s a one-and-done, right? That gives people this wonderful time off. In the relapsed/refractory setting, I think our goal is can we use CAR T to cure, right? That is the ultimate question. And, again, with cilta-cel (ciltacabtagene autoleucel) [Carvykti], with the original data from the LEGEND study, which was the original study in China, those patients had a little bit less therapy than CARTITUDE. However, there are about 15 percent of patients that are six years out from their CAR T still in remission, right?

And so that gives us a little bit of hope that maybe we’ll have a small tail and a small number of patients that are cured from our current CAR T approaches. But the question is, how do we now increase that tail and make it more like lymphoma? And then hopefully, 90, 100 percent of patients eventually, how can we, how can you get everyone cured? And so I think it comes down to myeloma is not the same for everybody, right? So you have our high-risk patients versus our standard-risk patients. And I think the strategies are going to be different for those two patient populations.

They already are in the way we treat patients with even induction therapy and maintenance and consolidation. We tend to be much more aggressive with folks who have high-risk disease versus those who don’t. And so, I think the biggest studies right now that are looking at this are really the combination studies. And so looking at CAR T followed by some type of maintenance, but fixed duration maintenance. So CARTITUDE 5 and 6 and KarMMa-9, these are all the studies of the BCMA CAR Ts in frontline. All of them will have maintenance afterwards, but it seems to be that they’re going to be two years of LEN maintenance and that’s it, nothing after that.

So LEN, lenalidomide (Revlimid), we know that it activates T cells. It activates other immune cells like NK cells in the body, even B cells. And so when you get cytokine release syndrome from the CAR T, you’re already making more of these immune cells and activating them. And now you’re going to have lenalidomide in there to kind of keep that going, right? And so that could help with this, not persistence of the CAR T itself, but persistence of better immune cells that can actually keep your myeloma down, right? So I think that’s one way.

The other way is some of the new therapies like CELMoDs. So these are sort of the newer version of lenalidomide and pomalidomide. They tend to have more immune effect than the other two drugs. So there’s studies looking at other CAR Ts, so a different target, right? So we talked about antigen loss. If you’ve lost BCMA, then what do we do?

Well, there’s other targets like GPRC5D. So a couple of the studies are looking at GPRC5D-CAR-T plus mezigdomide, which is one of the CELMoDs, or another arm is iberdomide, which is the other CELMoD, and looking at different doses without causing too many side effects, but still helping the T cell keep going, all kinds of things going on there. So those are some interesting studies.

And one of the cohorts, it’s actually using a GPRC5D-CAR-T with a BCMA bispecific after, that’s combinations. So now you’re targeting two different antigens and you’re using T cells in two different ways, right? And again, it’s fixed duration so that it’s not forever, but after a certain period, hopefully, we fix the bone marrow and we’ve killed enough myeloma that hopefully it won’t come back.

And so I think all of those are different strategies for the T-cell exhaustion to help with that, to hopefully keep from getting antigen loss, or if someone does have antigen loss, figuring out a way to go around it. And then the microenvironment I think is the biggest one, is how do we find cytokines and other things that can give us a bone marrow microenvironment that makes it really inhospitable for that myeloma to ever come back again.

So there are early Phase I studies looking at some of this, but I think down the line, that’s really what it will be, that once people go into their stringent CRs, MRD undetectable, now what can we do to keep that bone marrow from ever letting it grow again? And I think those are some interesting studies in the future.

Lisa Hatfield:

Okay. Thank you. So some patients are asked questions about the sequencing, and you’d mentioned different therapies. So I’ll ask this really quickly as follow-up, do you have any recommended or are there recommended sequencing of these different therapies like CAR T, then bispecifics, then CELMoDs, not all of them are FDA-approved at this point, but what are your thoughts on sequencing of those therapies?

Dr. Krina Patel:

So my activation tip here is that before you start bispecific therapy, talk to your doctor about CAR T. And the reason I say that is that when you get a bispecific therapy, and currently that is not a fixed duration therapy, it is a continuous therapy. So patients are on it until they relapse. And the problem is that once you relapse on that T-cell therapy, your risk of losing BCMA, losing the antigen is much higher. There are mutations that we’re seeing that most patients get.

So that means the next time we try to use a different BCMA therapy, there’s a big chance it’s not going to work. And we have small studies that show that, that people who get a bispecific, and then we try to go to CAR T for both CAR Ts that the response rates go down and the progression-free survival. So the months that patients get without, needing other therapy goes down for cilta-cel (ciltacabtagene autoleucel) [Carvykti], 33 months in CARTITUDE. It goes down to six months in CARTITUDE-2 where they did CAR T after prior BCMA therapy. That’s a huge drop.

In ide-cel, the real-world data, we saw that after bispecifics, you only get 2.8 months. If you get a CAR T, even though the response rates were still 70, 80 percent, it obviously there are clones that that BCMA isn’t there anymore that we can’t kill. And then it just grows back, right? The other way around, we actually see still a really good response because CAR T is a one-and-done, most of the time, you’re not going to lose BCMA.

So that let’s say a few years later, the myeloma was coming back. It usually has the same BCMA on there. So now I can use a bispecific. And yes, the PFS is still shorter than what you would see if you never had any BCMA therapy. It’s still in the realm of, almost a year, PFS though. So it’s much closer to what we see in the real world for bispecifics than the other way around for CAR T, it’s much, much lower. So we try to do CAR T first then bispecific, if possible. The other part is a T cell. So if you try to make T cells right after someone’s coming off of a bispecific, it is really hard to get T cells that are functional that then we can actually put a CAR into and make it work. So again, why, doing a CAR T first, and then a bispecific makes the most sense for the majority of our patients if they can do it that way.


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Are There Myeloma Trials Investigating CAR T for Frontline Therapy?

Are There Myeloma Trials Investigating CAR T for Frontline Therapy? from Patient Empowerment Network on Vimeo.

Is it possible for CAR T-cell therapy to be used as a frontline therapy? Expert Dr. Krina Patel from The University of Texas MD Anderson Cancer Center sits down with her patient, Lisa Hatfield to discuss CAR T-cell clinical trials, including CARTITUDE-4, KarMMa-2, and KarMMA-9, and trials currently under study. 

[ACT]IVATION TIP

“…talking to a myeloma specialist about different options that are out there for trials because different centers will have different trials that are open and you need someone to help you navigate with that. Which ones are the best ones for you? And then I would say talking to your patient advocacy groups, because that’s really where a lot of my patients hear the information. And then they come to me and say, ‘Listen, I heard this, what does it mean?’ And I think that really helps you kind of even know where to start from.”

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Transcript:

Lisa Hatfield:

So, Dr. Patel, for this next question, I’m going to preface it by saying that anybody that I have ever talked to in my advocacy work about myeloma and how to get care for myeloma, I’m a huge advocate for seeing a myeloma specialist. And I will tell everybody out there that Dr. Patel at MD Anderson is my myeloma specialist, and I’ve been with her since I was diagnosed in 2018. I live in an area where we don’t have any myeloma specialists. And so I’m an advocate for that. And anybody listening, I hope that they know that they can seek out the care of a specialist even for initial consult or even once throughout their journey.

Having said all that, I know Dr. Patel, because you’ve talked to me about them before, that you’re involved in some clinical trials for CAR T therapy. Can you talk a little bit about your trials that you’re doing right now that offer CAR T in earlier lines of therapy, including frontline therapy, and what this could mean for patients?

Dr. Krina Patel:

Yeah, no, I think the CAR T trials are what allowed us to even get to second and third line. The KarMMa-3 and  CARTITUDE-4 were the two trials that brought ide-cel (idecabtagene vicleucel) [Abecma] and cilta-cel (ciltacabtagene autoleucel) [Carvykti] forward, which is fantastic. And I think now it’s how can we improve even further? So some of our clinical trials are even earlier line, like you said, frontline. So we have one called KarMMa-9 that is for patients who have less than a VGPR, meaning that they didn’t get all their myeloma gone after their initial transplant, if they went to transplant, you can do consolidation with CAR T. And we’ve had a few patients that we did on a smaller study called KarMMa-2 that are doing really well after they were on that cohort for that study.

So that’s sort of why they’re doing a bigger study for FDA approval now. And then CAR T 2-5 and 6, we don’t have that at MD Anderson, but a lot of centers do. But that is now trying to see if cilta-cel can actually beat stem cell transplant, which again, a lot of us are really excited about, but we need to do the trial to make sure it’s just as safe and hopefully more efficacious. So I think those are really, really important. Auto-transplant, I was a transplanter when I first became faculty at MD Anderson.

And so I do think it has a role, but it’s high-dose chemo and there are secondary potential side effects that can happen. And people really have to kind of stop their lives for at least two, three months, if not longer, to go through that. Where in CAR T, I think it’s that quality of life piece. Again, it’s one and done. It doesn’t take as long to recover for the majority of patients. And it really is using immune therapy instead of chemo to kill that myeloma, right? So it is very different.

And we’ve seen some amazing depth of response for CAR T compared to what we see with the normal chemotherapy. So the other piece is how we have other trials that are doing earlier lines. So there’s new CAR Ts that are coming out, hopefully in the near future as a standard of care. So there’s one called ddBCMA. It’s a study by Arcellx. And the big news was that Kite, which is one of the big lymphoma CAR T companies, just took over to do their big Phase III study.

So hopefully we’ll have FDA approval for this in the next year with our Phase II study. But the Phase III will be in second line forward just like the CAR T 2-4 was. And this CAR T, it’s different in the way it’s built. And we really don’t see any of the neurotoxicity at all so far, which has been pretty impressive. But we see the same efficacy that we saw with cilta-cel. So this could be sort of best of both worlds, knock on wood. But so far we’ve seen some really great responses. And I think that trial being offered earlier will be great as well for a lot of our patients to get something that might be better than what we have already. The other trials are with other targets.

So we do have some studies that are looking at different targets instead of BCMA. So now we have patients who have already had CAR T with BCMA and over time, years, for the most part, they’re relapsing. And so now we have GPRC5D CAR Ts that are actually being combined with different things to then be able to give them a little bit earlier rather than waiting till after BCMA or fifth line, etcetera. So we have lots of trials looking at all different ways to combine CAR Ts or newer versions of the BCMA CAR Ts that I think are really, really exciting. And I think it’s really hard to keep up with this.

So my activation tip here is really talking to a myeloma specialist about different options that are out there for trials because different centers will have different trials that are open and you need someone to help you navigate with that. Which ones are the best ones for you? And then I would say talking to your patient advocacy groups, because that’s really where a lot of my patients hear the information. And then they come to me and say, “Listen, I heard this, what does it mean?” And I think that really helps you kind of even know where to start from.


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What Patient Types Are Good Candidates for CAR T-Cell Therapy?

What Patient Types Are Good Candidates for CAR T-Cell Therapy? from Patient Empowerment Network on Vimeo.

For CAR T-cell therapy, what patient types are good candidates? Expert Dr. Krina Patel from The University of Texas MD Anderson Cancer Center discusses patient situations that qualify them for CAR T-cell therapy and shares proactive patient advice.

[ACT]IVATION TIP

“I think a lot of people have this misunderstanding that CAR T isn’t for everybody, but I will say it’s actually more likely that you’re going to be eligible for CAR T over auto transplant. So I think it’s just bringing it up, talking to them, and seeing a specialist to discuss which ones are the right one for you and when to go.”

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Transcript:

Lisa Hatfield:

Dr. Patel, given that CAR T is approved for earlier lines of therapy, can you describe the type of disease characteristics of patients that are likely to be considered first for CAR T?

Dr. Krina Patel:

Yeah, I think it’s a really exciting time, we got approval for two different CAR Ts that were approved in fifth line. So patients had to relapse four times before they could get to CAR T therapy. And now one of them, cilta-cel ciltacabtagene autoleucel [Carvykti], is approved in second line, so people have to relapse once before they can get it.

And the other CAR T, ide-cel (idecabtagene vicleucel) [Abecma], is approved in third line, so you have to relapse twice. There are reasons why that is the way it is, but both of these CAR Ts are pretty fantastic, and we’re really excited that more patients will now have access. As you can imagine, relapsing once, it’s already hard enough to then say, okay, I need a different therapy, but to go through four times before you can do something like CAR T is really, really important.

So I think the biggest characteristic, and I would say for my patients, it’s really their ability to keep their myeloma controlled for at least six to eight weeks, potentially, right? Because this is a personalized therapy, unlike most other myeloma therapies where we have to take the T cells out, we have to then send them to a lab to make the CARs, then it takes about four to six weeks to get them back. During that time, I just have to know that your myeloma can stay controlled or even improve with whatever bridging therapy we decide to do during that time.

And we know that when patients have myeloma that is on its way down, that it’s actually improving, by the time they get to the CAR T therapy, the infusion part, they tend to do better in terms of efficacy, but also have less toxicity. So there’s a few different toxicities that we can talk about with CAR T that are very distinct compared to most other therapies, that again, if you have less disease burden, the rates of that toxicity and the high-grade toxicity goes away, right? It’s much, much lower than if you have a lot of myeloma coming in.

So, again, for my patients who have disease that I know I have other therapies to keep it knocked down or to knock it down during that bridging, that really is the main difference between, can I take this patient to CAR T or not? But I think there’s some nuances too, again, that idea that one CAR T is approved in second line, another one is approved in third line, I do think they’ve never been tested head to head, so we don’t have data in a clinical trial, but in the real world, we’ve used both of these products, a lot of us have, and I think most of us will say that one of the products is probably stronger, it probably works better cilta-cel, and that is the one that’s approved in second line, which is great.

So for my fit patients who don’t have a lot of comorbidities, who do really have high-risk disease that I need to be as aggressive as possible and do something very different, hands down, it makes sense that cilta-cel is the right thing to do right at second line, but the toxicity is also a little bit higher with that, meaning that patients are more likely to potentially get some of these strange neurotoxicities that we see, that we didn’t really see before with other therapies, some of our myeloma patients get neuropathy and we think about that as neurotoxicity, but this is different.

This is more patients after 30 days of having had their T cells can all of a sudden get a facial palsy where they’re having drooping of their face and it can affect their eating and their speaking. Now those things are not fatal, we can treat it with steroids, things like that, but they can affect your quality of life. And if it doesn’t resolve, that can affect down the road, all the other therapies we want to give you, right? But the more dangerous one is something called delayed Parkinsonianism or delayed motor neurotoxicities.

And again, we know the best prevention of that is decreasing the myeloma burden before going to CAR T, but if we can’t do that or some patients can still potentially get this Parkinsonianism, we really want to make sure there’s a risk-benefit discussion, right? That we say, okay, this is why we should go in second line.

Again, the risk is less than 1 percent now based on how we’ve done things for prevention. But on the other hand, with ide-cel, most of our patients, even on dialysis, our patients that are getting CAR T and doing well, patients with heart failure, I’ve had a 90-year-old go through ide-cel without any issues and have great responses. So I think both of these offer, one of the first times they offer time without any therapy for myeloma. And so I would say this is something most of my patients should ask their physicians about, but really then it’s nuanced in terms of when we should do it and which product.

Lisa Hatfield:

Okay, thank you. And do you have an activation tip for that question, Dr. Patel?

Dr. Krina Patel:  

Yeah, so I think the activation tip here is bring it up, bring up CAR T to your doctors, right? I think a lot of people have this misunderstanding that CAR T isn’t for everybody, but I will say it’s actually more likely that you’re going to be eligible for CAR T over auto transplant. So I think it’s just bringing it up, talking to them, and seeing a specialist to discuss which ones are the right one for you and when to go.


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Developing Research and New Myeloma Treatment Options

Developing Research and New Myeloma Treatment Options from Patient Empowerment Network on Vimeo.

What are the new developments in myeloma treatment and research? Dr. Brandon Blue discusses how the landscape of myeloma care has changed in recent years and treatment options for high-risk myeloma, and he shares developing research that patients should know about.

Dr. Brandon Blue is Assistant Member and Clinical Instructor in the Department of Malignant Hematology at Moffitt Cancer Center in Tampa, FL. Learn more about Dr. Brandon Blue.

See More from Evolve Myeloma

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How Is High-Risk Myeloma Assessed

How Is High-Risk Myeloma Assessed?

Transcript:

Katherine Banwell:

Dr. Blue, the landscape of myeloma care has changed significantly in recent years. Are there new factors to consider when working with a patient to choose a treatment approach?   

Dr. Brandon Blue:

Yeah. The good thing about myeloma is it’s literally always changing, and that’s a great thing. Compared to some of the other cancers, or really even other diseases, sometimes we’ve been using the same things since the ‘90s. But luckily for myeloma every couple years we get something that’s bigger, and typically better. So, right now some of the new things that are available for patients are all the way from newly diagnosed, all the way to people who have relapsed disease. So, we have a lot of different options that we can potentially go into.  

Katherine Banwell:

Dr. Blue, what treatment options are available for myeloma that’s considered high-risk?  

Dr. Brandon Blue:

Yeah. So, unfortunately, there’s some people who have multiple myeloma whose disease does not follow the standard pattern. Unfortunately, what happens is that there are certain mutations that actually happen in the biology of those cancer cells that actually cause them to survive when they should be dying. And unfortunately, that means that sometimes the chemotherapy and the medicines that we give them becomes a little bit more resident. 

A lot of times when we give people treatment the one question they ask is, “How long will it last?” But, unfortunately, there’s some people who have those high-risk features that unfortunately, despite whatever numbers we tell them of how long it may last, theirs actually may last a little bit shorter, and the disease may come back a little bit quicker. So, what we have to do as the doctors, and as the team, taking care of these patients is maybe do things a little bit more outside of the box, and do things that might tend to be a little bit more aggressive. 

Because sometimes we have to match the aggressiveness of the disease. If the cancer itself is starting to be high-risk or aggressive, sometimes we may have to do some nontraditional things to kind of make sure that they have a good outcome and a good result.  

Katherine Banwell:

Dr. Blue, is there developing research that myeloma patients should know about? And what are you hopeful about?  

Dr. Brandon Blue:

Yeah. One of the things that happens right now is that we have CAR T that’s available for patients got approved by the FDA. However, the CAR T product that we currently have available only have one target, which is called the BCMA, or B-cell maturating antigen. 

Which is part of the plasma cells, however, there are so many other targets on the plasma cells that potentially can be targets for new medications. And the good thing is that there are actually new CAR T and medications that are being developed that actually target other things other than the BCMA.  

So then, it may come to the point where people get more than one CAR T down the road, and I think those are exciting clinical trials. Because if there’s multiple targets, and there’s multiple CAR T, maybe we can sequence them in a way that maybe we find a cure for the disease one day.  

Katherine Banwell:

That’s exciting.  

Dr. Brandon Blue:

It is.  

Katherine Banwell:

Dr. Blue, thank you so much for joining us. Do you have anything else you’d like to mention?  

Dr. Brandon Blue:

I just want people to know that it’s okay to get a second opinion. I think that regardless of what’s happening in your care, sometimes it’s always good just to have someone, especially someone who’s what they call a myeloma specialist, to review your case, and just make sure that you’re on the right road, and that things are going well for you. So, it’s something that I would recommend for anyone to do. 

What Emerging Myeloma Treatments Are Showing Promise?

What Emerging Myeloma Treatments Are Showing Promise?  from Patient Empowerment Network on Vimeo.

Myeloma specialist Dr. Mark Schroeder reviews the latest advances in myeloma treatment, including a discussion of CAR T-cell therapy and bispecific antibodies.

Dr. Mark Schroeder is a hematologist at Siteman Cancer Center of Washington University School of Medicine in St. Louis. Dr. Schroeder serves as Associate Professor in the Department of Medicine. Learn more about Dr. Schroeder.

See More from Engaging in Myeloma Treatment Decisions

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Transcript:

Katherine Banwell:

What about emerging therapies for myeloma? What approaches are showing promise? 

Dr. Mark Schroeder:

So, I think the biggest news in myeloma, and across a lot of cancers now, are immunotherapies. We know in myeloma – now we have two CAR T-cells –  

Now a CAR T-cell is engineering your own immune cell called a T cell to express a receptor on its surface that binds to the myeloma, and then those immune cells go and kill the myeloma. That’s a form of immunotherapy.  

There’s two CAR-T cells for treating myeloma after the myeloma has come back four times, has needed four treatments. Those are very active in that line of therapy, and we can see response rates over 80 percent in patients who otherwise weren’t responding to other approved therapies for myeloma.  

On the other hand, there are other immunotherapies that are used earlier in the treatment course of myeloma. One that is not incorporated more frequently for the initial treatment is a drug called daratumumab – it’s an antibody. It’s a protein that binds to the surface of myeloma and stimulates the immune system to react against the myeloma. And so, it’s not a traditional chemotherapy, but it’s using your own immune system to attack the cancer.  

And then a third one that’s probably just as – it looks just as potentially effective as CAR-T cells are called bispecific antibodies. And that would use a protein similar to daratumumab which is an antibody, but it uses parts of antibodies to bind to – it could be two different proteins – one expressed on a T cell, the other one expressed on the myeloma cells. And when it binds, it brings those two cells together and causes your own immune system to attack the myeloma. Those are also very effective, and within the next month or two, there will be a bispecific antibody approved for treating patients with myeloma. 

Katherine Banwell:

Oh, that’s great news. Any others? 

Dr. Mark Schroeder:

Yeah, well – I mean, the other potential – there are other immune cells called natural killer cells that are also in clinical trials for development to attack myeloma, and potentially even engineering those natural killer cells to attack myeloma.  

There are other antibodies; sometimes the antibodies of protein bind a specific target on the surface of the myeloma. I mentioned one – daratumumab – but there is a whole list of others that are in clinical development. The one other antibody – or two, couple of other antibodies that are approved for treating myeloma are isatuximab which also binds to CD38. And another one called elotuzumab which binds to a protein called CS1 or SLAMF7 on the surface of myeloma.  

That’s more information than you probably wanted or needed, but those antibody therapies can be very effective in treating myeloma. There is another antibody therapy that has a payload of a toxin on the antibody, and it binds to BCMA or B-cell maturation antigen.  

That’s the same antigen that the bispecific antibodies as well as the CAR-T cells are targeting on myeloma surface, and so that is potentially one that is approved by the FDA also to treat myeloma.   

Katherine Banwell:

As we close out our conversation, Dr. Schroeder, I wanted to get your take on the future of myeloma. What makes you hopeful? 

Dr. Mark Schroeder:

Well, I am hopeful – just within the last five years, there have been a number of new drugs approved for myeloma. They are approved for later lines of therapy, but they are being moved earlier in the treatment. And within the last 10-20 years, we’ve seen an improvement in the survival of patients with myeloma. As these new therapies are in development, as they’re being moved earlier in the treatment line, I’m very hopeful that survival and potentially cure for this cancer is possible. The only way that we’re going to get to that point is through clinical research and for patients to partner with their physicians and to consider clinical trials because that is the only way that new drugs get approved and are available to other patients with myeloma. So, I’m excited about what is approved; I’m excited about what’s coming through the pipeline to treat myeloma.  

Key Factors That Guide Myeloma Treatment Decisions

Key Factors That Guide Myeloma Treatment Decisions from Patient Empowerment Network on Vimeo.

Treatment for myeloma varies from one patient to the next. Dr. Joshua Richter, a myeloma specialist, reviews the factors that are considered when choosing a treatment approach.

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

See More from Thrive Myeloma


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Transcript:

Katherine:

What I would like to look at is because everyone’s different, what’s going to work for one patient might not work for another. So, how do you choose which treatment is right for a patient? 

Dr. Richter:

Really great question. So, unfortunately, myeloma, we don’t have the granularity just yet to say exactly what’s going to work for everyone. Our goal is to kind of be what I like to think of as urinary tract infections. You have a UTI, you pee on a dish, we put little discs of antibiotics and a couple of days later, we’re like, “You have an E. coli and Cipro will work.” You get the Cipro, and it goes way. We don’t really have that outside of a few drugs. We do know that the drug venetoclax (Venclexta) works really well in people who have a very specific type of translocation in their myeloma cells, something we call translocation (11;14).  

But for the most part, we don’t know, and we have lots of options and we decide what drugs to use based on three factors: disease-related factors, treatment-related factors, patient-related factors. So, patient-related factors. Are you older or younger? Fit or frail? Do you have comorbidities? If you have a lot of neuropathy from diabetes, I don’t want to give you a drug that’s going to cause more neuropathy. If you have a lot of cardiac issues, I’m not going to give you a cardiac drug. Disease-related factors. Is your disease growing fast or slow? Can I give you some pills or do I need to give you intravenous immediately to stop it? Is it pressing on a nerve? Do I need to add radiation?  

So, those are some of the big factors. And then, treatment-related factors. Have you had certain other drugs? So, if you’re refractory to lenalidomide (Revlimid), I may not want to give you Revlimid again. 

If you have a lot of side effects or didn’t respond well to Revlimid, I may not want to use another drug similar to Revlimid like pomalidomide (Pomalyst).  

I may want to choose another class. So, that’s kind of putting all of that together to come up with a treatment choice because there’s no clear guideline. 

Myeloma Treatment & Research Updates From 2022 ASCO and EHA Meetings

Myeloma Treatment & Research Updates From 2022 ASCO and EHA Meetings from Patient Empowerment Network on Vimeo.

Myeloma specialist and researcher Dr. Krina Patel discusses highlights from the recent American Society of Clinical Oncology (ASCO) annual meeting and the European Hematology Association (EHA) 2022 Congress. Dr. Patel shares promising research updates related to approaches including: stem cell transplant, CAR T-cell therapy, and bispecifics.

Dr. Krina Patel is an Associate Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center in Houston, Texas. Dr. Patel is involved in research and cares for patients with multiple myeloma. Learn more about Dr. Patel, here.

Related Resources:

How Does Immunotherapy Treat Myeloma?

What Is Myeloma CAR T-Cell Therapy?

Immunotherapy: Which Myeloma Patients Is It Right For?

Transcript:

Katherine:   

Dr. Patel, cancer researchers recently came together at the annual ASCO and EHA meetings. Are there any highlights from the meetings that myeloma patients should know about?

Dr. Patel:    

Yeah, so we had some amazing trials that were presented at both. And I got to actually go to Chicago for the ASCO meeting, and I’ll say we actually had a plenary session that was presented for myeloma. That doesn’t happen as often as we like. So, basically that was a study presented by Dana-Farber and all of the different groups around the U.S. that did a transplant study. And basically, they’re looking at patients who got induction therapy when they’re newly diagnosed with transplant versus they didn’t get transplant upfront. And it’s called the DETERMINATION study, and it was to determine should everybody be getting a stem cell transplant.

Katherine:  

Right.

Dr. Patel:   

And this is a trial that’s been going on for over 10 years; that’s why it was so highly anticipated. And basically, the biggest thing that we saw was what we call progression-free survival; so, the time that the myeloma hibernates is what I call it, for PFS. Basically, patients who got transplant upfront, it was 21 months longer that it stayed hibernating than if you didn’t get transplant upfront. So, that’s the trial, that’s what it was looking at, and that’s all they could really say about it. The good news is, even patients who didn’t get transplant upfront but then got transplant in second remission tended to have a really good, long progression-free survival or hibernation in that second remission.

So, it still tells us that right now, a transplant is still important for the majority of our myeloma patients. And basically, that’s sort of what that trial showed.

Now, the difference is we do different types of upfront therapies, and we have new things like CAR T and bispecifics that are coming up earlier. So, we’ll see in the future if it still holds up. But as of right now, it still holds up for transplant. The other big studies, of course, were some of our bispecific studies that use different antigens. So, antigens are the flags that are on the myeloma that we make these receptors for CAR T, so they can find the myeloma, or bispecifics go after that.

And basically, there are other antigens. BCMA, B-cell maturation antigen, is the big one that we use for everything right now. But now, we found even more antigens, which is fantastic.

So, we have something called FcHR5. We have something called GPRC5D. It’s like alphabet number soup, basically. But what’s really exciting is that these new antigens give us a different way of getting to that myeloma, especially if someone has already had a BCMA therapy and they’ve relapsed on that. Well, now we have even new ways to get to that myeloma cell. So, I think that’s some really, really exciting data.

And then, I’ll say the other big one was one of the CAR Ts, Cilta-Cel was something that they presented.

Again, this was two years after the last patient had gotten treated on the trial. And so far, they still have about 71 percent of patients that are still in remission two years after. So, that is huge.

Katherine:                  

Wow.

Dr. Patel:  

We’ve never seen that in relapsed refractory patients before, so we’re really, really excited to kind of have gotten that data to say, “Okay, we found a brand-new way of treating myeloma.” And it really is changing how we’re looking at even earlier lines of therapy now.

Katherine:   

Such promising news. That’s great.

Thriving With Myeloma: What You Should Know About Care and Treatment

Thriving with Myeloma: What You Should Know About Care and Treatment from Patient Empowerment Network on Vimeo.

What does it mean to thrive with myeloma? Myeloma specialist and researcher, Dr. Joshua Richter discusses the goals of myeloma care, reviews treatment options –including research updates – and shares tools for taking an active role in decisions.

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

Download Guide

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Updates in CAR T-Cell Therapy for Myeloma from ASH 2021


Transcript:

Katherine:

Hello, and welcome. I’m Katherine Banwell, your host for today’s program. Today’s webinar is about how to live and thrive with myeloma. We’re going to discuss myeloma treatment goals and how you can play an active role in your care. Before we meet our guest, let’s review a few important details. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you. Let’s meet our guest today. Joining me is Dr. Joshua Richter. Dr. Richter, welcome. Would you please introduce yourself?

Dr. Richter:

Hi. Thank you for having me today. My name is Joshua Richter.

I’m an associate professor of medicine at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai and the director of myeloma at the Blavatnik Family Chelsea Medical Center of Mount Sinai.

Katherine:

Great. Thank you for taking the time to join us today. There were two major cancer meetings recently, ASCO and EHA. Are there research updates from those meetings that myeloma patients should know about?

Dr. Richter:

Absolutely. These are some of the biggest meetings that we have every year that attract all types of people, patients, caregivers, physicians, nurses, Pharma, even investors from all over the world. We’re coming off of the back-to-back American Society of Clinical Oncology and European Hematology Association meetings, and there were a couple of really important updates and data. One of them at ASCO actually had what we call a plenary session.

A plenary is the top type of session at any one of these congresses, and it was around something called the DETERMINATION trial which looked at something a lot of patients may be familiar with, the notion of getting VRd, Velcade, Revlimid, and dexamethasone, with or without getting a stem cell transplant as part of their initial treatment. Now, many years ago when our initial therapy was not so good, we showed that transplant was better than what was good 30 years ago.

But, we have better treatments now. So, do we still need high-dose chemotherapy and stem cell transplant?

And what was really interesting about this data set is that if you do get a transplant upfront, you do seem to have a longer PFS, progression-free survival, meaning you stay in remission longer if you get your transplant as part of your initial therapy. However, there was no difference in overall survival, meaning how long you actually lived. And this may not make a lot of sense at first, but think about patient one who stays in remission longer, but because now their disease is a little more refractory, the subsequent therapies don’t work as well as compared to the person who doesn’t get the transplant upfront.

And then those latter therapies work a little better, and when you add them all up, they come out about the same. So, I think one of the things that comes out of this is, “Do I need the transplant?” No, you don’t need the transplant as part of your initial therapy.

We’re still trying to figure out who really needs it and who doesn’t, but you can always never do it or save it for a later time. So, that was really one of the big things that came out of the ASCO meeting.

Katherine:

What about EHA?

Dr. Richter:

So, EHA had a lot of updates both in terms of CAR T-cell therapies and bispecific antibodies, and bispecific antibodies are near and dear to my heart. They’re my big passion in myeloma, and I had the honor of presenting updated data on the Regeneron 5458 bispecific antibody at EHA.

This is a BCMA CD3 bispecific. So, many people may be familiar with monoclonal antibodies like daratumumab, which is just an antibody that gets injected and attacks the cancer.

Bispecifics are molecules that are injected that have two arms. One grabs onto the cancer cell; the other grabs onto your own immune cells that we call T cells and activates them to attack the cancer. Very interesting new therapy.

Very exciting, and very high response rates in people who have had tons and tons of treatment. So, in people that have seen almost everything in the highest dosing group of the study, 75 percent of people responded, which is very, very high.

But more notably, the big side effect we look out for called CRS or cytokine release syndrome, that’s where we activate your T cells and they get so activated they can cause other problems. That can be pretty high in some of our immune therapies, but in this drug, there’s only 38 percent, and all of this was relatively minor. It wasn’t the really big stuff.

So, the reason why this is so near and dear to my heart is that some of these therapies like CAR T have to be given in a major center that does transplants.

But bispecific antibodies, if put together the right way, can be given in your local hematologist’s, oncologist’s office. So, a lot of great potential long-term get everybody treated with these drugs. And then, one or two other little things that I thought were really huge, one was the combining of bispecific antibodies. Studies called the TRIM protocols combined two different bispecific antibodies, one called teclistamab, and one called told talquetamab. Each got combined with daratumumab.

So, not only are we already seeing just the bispecific by itself, we’re starting to combine it and seeing unbelievable response rates. That was updated at EHA, which was groundbreaking. And then in CAR Ts, two things really caught my mind. One was the CARTITUDE-2 data basically giving CAR Ts earlier on to patients had a 100 percent response rate. Can’t really do better than 100 percent. So, it’s not just about getting 100 percent of people in remission.

It’s keeping them there and curing them, and it starts by getting 100 percent of people to respond. So, really looking forward to see how this develops.

But one of the other things was another CAR T that’s coming out of China that targets two different things. It targets BCMA and CD19, both of which can be found on myeloma cells, although CD19 is actually on the myeloma stem cell. It’s a little kooky. But one of the big issues with CAR Ts is manufacturing time. Right now, it takes four to eight weeks to make them. But in this construct, they were able to make them, it took them between 22 and 36 hours. So, for many people, they were able to manufacture the CAR Ts, theoretically, for patients within one day.

So, if we can not only get this therapy to work but shrink the manufacturing from a month or two to a day or two, that would make this more accessible to more patients, get them to their treatment on time. So, the sky’s the limit with our immune options right now.

Katherine:

Excellent. Since this webinar is part of Patient Empowerment Network’s Thrive series, I thought we could start by getting your opinion on what you think it means to thrive with myeloma.

Dr. Richter:

Absolutely. And I love that term. I recently chaired a 5K walk for the MMRF, and the word that is thrown around a lot in cancer is “survivorship.” And, I got up there and I said, “That’s not a word I like to use. I like to use the word “thrivorship.” So, I love that you’re using this word because to me, surviving is an important part of dealing with cancer, but it’s the first step. Thriving is the goal. The goal is not to just get through it. It’s to go beyond it. It’s to do everything you want to do in life: personal, family, business, anything you want.

If you want to spend your time fishing, if you want to spend your time skydiving, if you want to spend time with your grandkids, and enjoying that time, and as much as humanly possible, keeping the notion of cancer way out of your brain. To me, that is thriving and not just surviving with a diagnosis like myeloma.

Katherine:

That helps us guide through the conversation as we continue on. Getting the appropriate myeloma care is, of course, part of thriving. So, let’s talk about treatment. How would you define treatment goals?

Dr. Richter:

Sure. So, treatment goals are different for each different individual because unfortunately, myeloma tends to affect people who are older. So, whereas the goals for an 85 or 90-year-old diagnosed with the disease is maybe things like, “I don’t want to suffer. I don’t want to have as many side effects,” but the goal is not to live 40 years, that’s different from a 40-year-old who may say, “I’m willing to tolerate certain side effects because I want to live as far as possible.” So, in reality, there always has to be this huge balance. And as with anything in medicine, an open dialogue with your care team is crucial to understand what your goals are because a lot of us make assumptions on both sides.

The patient may assume that we want certain things out of this. We may assume the patient wants certain goals. Really open, vibrant discussions where there are no taboos, there’s nothing wrong to say. I’ve had patients say, “I don’t care what happens. My granddaughter is getting married next year. I need to be there.

Anything beyond that, I don’t care.” That’s their goal. They’re entitled to their goal. I will work with them within that construct. So, really being open about what the goals are. Right now, what I tell patients is, especially for younger patients who if you’re already 85 or 90, you’re getting closer and closer to how long you’re likely to survive even without myeloma.

It’s kind of hard to have a 90-year-old have a 30-year survival. We’re not living to 120 just yet anyway. But for most of my patients, I say my goal is to either keep you in remission so long that you pass from something else many years from now, or to keep you moving until we have a cure that we can just give you and then make sure that that cure, that you’re able to accept it. That your body’s intact, your bone marrow’s contact, and this is something we can provide for you.

Katherine:

Well, tell me what you think the patient’s role is, then, in setting care goals.

Dr. Richter:

Absolutely. The patient has the most crucial role of course. And, one of the things is honesty and really being to a point of brutal honesty with how they’re doing. I always tell patients, “You don’t get extra points for suffering. It’s not that if you sit there in pain you’re going to do better. Let me know what type of pain you’re having.” And pain doesn’t just mean a bone is hurting, or a muscle’s hurting, we call somatic pain.

There can be neuropathic pain where the nerves hurt.

There can be emotional and spiritual pain. These things all need to be addressed. And if you are suffering in silence, we have a lot of tools nowadays not just medicines. We have people to talk to. We have resources. So, letting us in to help is one of the most crucial things because we’ve actually shown that if you actually improve some of these, you may actually improve overall outcomes. So, the patient, please, all we want to do on the care side of the equation is help.

Let us know what’s bothering you. It may be small to you, it may be big to us, or vice versa, but the more open you are, the better we can help.

Katherine:

Yeah, that’s great advice. Before we move on to discussing how the treatment choice is determined, let’s define a couple of terms that are often mentioned in myeloma care. What does it mean to be refractory and how is that different from relapsing?

Dr. Richter:

Great question. So, these terms have very specific definitions in myeloma. “Relapsing” just means that the disease is coming back. So, you had myeloma that was measurable, you went into a remission, and now it is showing signs that it’s coming back. We call that “relapsing.” And depending upon what type of myeloma, we have specific definitions. So, if you’re IgG kappa and you make an M-spike, if your M-spike goes up at least 0.5 and at least 25 percent, we call that “relapsing.” If you’re a light chain, it’s gotta go up by at least 100. But, you’ve gotta make sure the units are right.

“Refractory” means that you either did not respond or you’re progressing on or within 60 days of your last treatment. So, I put you on Revlimid maintenance, and you’re on Revlimid, and your disease gets worse. You are now relapsed and refractory to Revlimid. If I give you a transplant and then I put you on nothing, and two years later your disease comes back, you’re relapsed but not refractory.

Katherine:

What I would like to look at is because everyone’s different, what’s going to work for one patient might not work for another. So, how do you choose which treatment is right for a patient?

Dr. Richter:

Really great question. So, unfortunately, myeloma, we don’t have the granularity just yet to say exactly what’s going to work for everyone. Our goal is to kind of be what I like to think of as urinary tract infections. You have a UTI, you pee on a dish, we put little discs of antibiotics and a couple of days later, we’re like, “You have an E. coli and Cipro will work.” You get the Cipro and it goes way. We don’t really have that outside of a few drugs. We do know that the drug venetoclax works really well in people who have a very specific type of translocation in their myeloma cells, something we call translocation (11;14).

But for the most part, we don’t know, and we have lots of options and we decide what drugs to use based on three factors: disease-related factors, treatment-related factors, patient-related factors. So, patient-related factors. Are you older or younger? Fit or frail? Do you have comorbidities? If you have a lot of neuropathy from diabetes, I don’t want to give you a drug that’s going to cause more neuropathy. If you have a lot of cardiac issues, I’m not going to give you a cardiac drug. Disease-related factors. Is your disease growing fast or slow? Can I give you some pills or do I need to give you intravenous immediately to stop it? Is it pressing on a nerve? Do I need to add radiation?

So, those are some of the big factors. And then, treatment related factors. Have you had certain other drugs? So, if you’re refractory to Revlimid, I may not want to give you Revlimid again. If you have a lot of side effects or didn’t respond well to Revlimid, I may not want to use another drug similar to Revlimid like Pomalyst.

I may want to choose another class. So, that’s kind of putting all of that together to come up with a treatment choice because there’s no clear guideline.

Katherine:

Right. Can you help us understand some of the common issues that myeloma patients experience and how they might be managed?

Dr. Richter:

Sure. So, fatigue is an absolutely huge one. And fatigue can come from a lot of different things. One, fatigue can come from other medicines. A lot of patients have cardiac issues and may be on other medicines causing fatigue. So, optimizing your other clinical status is important. Anemia can lead to fatigue, so we monitor your blood counts very closely, and if they drop, can we provide medicines to boost them up? Drugs. Some of the therapies we have can cause fatigue, and one of the biggest ones is Revlimid.

And, I tell people what actually tends to help is you take the Revlimid at night instead of the morning because if you take it at night, it tends to maximize the fatigue while you’re already sleeping. If you take it in the morning, it tends to maximize at that horrible, coffee-needing hour of 3:00 p.m. to 4:00 p.m., or 4:00 p.m. to 5:00 p.m. where you’re like, “Oh, I’ve gotta lie down.” So, fatigue is a really big one. Neuropathy. Neuropathy is really getting less and less in our new patients because more of our modern drugs don’t cause it, but unfortunately, some patients still have neuropathy and they may be using drugs like gabapentin or Lyrica.

There’s some other really old drugs and new drugs that can help. Drugs like Pamelor, which is nortriptyline, or Cymbalta may help quite a bit, or another drug called Effexor. And, many of these drugs may be used for

anxiety and depression, but also work for neuropathy. And then, even going to things like the cannabinoids; things like marijuana derivatives may actually be able to help both in salves or even edibles may actually help some of the neuropathy issues. And then, we get into some kind of out there stuff like compounding ketamine to help with some of these salves or oral combinations. So again, a little bit of neuropathy, let us know because there may be some ways to help.

Katherine:

Are kidneys impacted by any of the medications that patients take?

Dr. Richter:

So, kidneys are an excruciatingly important part of myeloma, and d in my mind, one of the keys to long-term survival and outcome. So, there are three things that I tell all of my patients to help preserve long-term kidney health. Two of them are easy to wrap the head around. One is a little bit harder. Number one, keep yourself well hydrated. The kidneys are like a filter. Think, like, the filter for your car. If you drove 100,000 miles in the desert and didn’t change your oil, there’d be problems. So, especially now that there’s warmer weather, by the time you already feel yourself dehydrated, you’re about 10 to 15 percent low on the total amount of body water you need.

So, especially if you’re going out there doing yard work, playing with the kids or grandkids, make sure you’re drinking plenty of water. Two, avoid NSAIDs. Drugs like Aleve, or naproxen, or Advil, or ibuprofen can be harmful to the kidneys. So again, please discuss with your care team. There may be better alternatives to treat your pain without hurting the kidneys. And the third is when all else possible, and avoid intravenous contrasts for CAT scans. Now, the IV contrast you get for MRIs is called gadolinium. It’s not harmful to the kidneys. But, the contrast for CAT scans is iodine-based, and although the newer formulations are better, it can still hurt the kidneys.

So, my advice is the following. If you’re in the ER at 2:00 a.m. in the morning and they want to do an urgent CAT scan with IV contrast, let them do it. It’s likely not going to be an issue. If you go to see an orthopedist and they say, “I want to get a better look at that leg that’s bothering you. I’m going to get a CAT scan with IV contrast,” tell them to call me. We’ll find an alternative.

Katherine:

Okay. All right. Good advice. Thank you. So, once treatment has begun, how do you know if it’s working?

Dr. Richter:

Absolutely. So, the majority of myeloma patients are what we call “secretory.” And by “secretory,” it means that the cancer cells secrete a protein that we can measure in the blood either an M-spike, which is an intact immunoglobulin like IgG and kappa, or a free light chain. It doesn’t make that IgG part, just a free kappa or free lambda. And basically, when these protein levels go up, we know the cancer cells are growing. When these go down, we know we’re killing the cancer cells. And we actually call your remission based on how much we lower it.

If we lower it 25 to 49 percent, that’s an MR or minor response, or minor remission. 50 to 89 percent is a PR, partial response, partial remission. 90 to 99 percent is a VGPR, a very good partial remission, and then all gone in the blood and then we do a bone marrow is a CR or complete remission.

For some people, their disease can be non-secretory where the cancer cells don’t make that protein anymore.

And for those people, we need to do regular imaging to see if they have growths of myeloma we call plasmacytomas, or unfortunately, we need to do regular bone marrow biopsies to see how much of the bad cells are growing inside the marrow.

Katherine:

All right. How do you know when it’s time to switch treatment?

Dr. Richter:

So, in general, when patients fulfill the criteria for what we call “progressive disease” or PD, that’s the time to change, or intolerance that regardless of how we dose adjust, dose hold or add supportive care, it’s not tolerable for a patient to continue.

Intolerance is a very personal thing. There are things that certain people are willing to tolerate and others not. So, we try to adjust that. Just like we have criteria for response, PR, VGPR, we have criteria for progression. And in general, it’s a 25 percent increase from your baseline and 0.5 increase in your M-spike or 100 increase in your light chains. So, when the disease numbers are going up, we tend to switch.

Now, people may say, “But I feel fine,” and a lot of this is because you’re diagnosed with an amount of disease up here. We get you in remission, you’re down here. And once you go like this, we can see the writing on the wall and we’d rather be proactive than reactive. So, instead of waiting until the numbers get up here to cause trouble, once it goes from there to there, we intervene, change therapy to bring it back down.

Katherine:

Dr. Richter, why is it essential for patients to share any issues they may be having with their healthcare team?

Dr. Richter:

It is absolutely crucial because some things that may be very, very minor to them may be the tip of the iceberg of something very, very worrisome that we really need to investigate because sometimes, little problems are little now, and over time, they can become problems that we can’t so easily reverse. So, things like neuropathy, fatigue, or actually better yet, what I tell my patients is, “You know your body. If there is something out of the ordinary, big or small, let us know.”

And I would way rather a patient tell me 10 things in a row that mean nothing than not tell me about that one thing that means something.

So, for example, one of the disorders that’s associated with myeloma is called amyloidosis.

And when amyloid attacks the kidneys, you start to have protein in the urine, and this looks like bubbles, like foam in the urine. So, if someone has no foam when they urinate, and then over a period of months to years, they’re starting to notice lots of foam, tell me because that means we may need to look for things like amyloid. So, really any time something changes.

Katherine:

Anything. Yeah. I want to make sure that we get to some of the audience questions. So, let’s start with this one. PEN community member Sal sent in this question prior to the program. “What is the difference between myeloma and multiple myeloma?”

Dr. Richter:

A really great question. For the most part, the terms are synonymous. We abbreviate multiple myeloma as myeloma. But along those lines, and I literally saw a patient today who said, “Why is it called multiple myeloma?” Well, when you have a group of bad plasma cells that forms a tumor, we call that a plasmacytoma, “cytoma” meaning “bad cells,” and “plasma” because they’re plasma cells. And when you have one of them, it is a solitary plasmacytoma. Once you have two of them, it’s multiple myeloma because it’s in multiple spots in the marrow or multiple spots in the body. So, for our purposes, we use them interchangeably, but that’s where the “multiple” comes from.

Katherine:

Okay. Isaac sent us this question. How long does the average myeloma patient remain on Revlimid? And, is there a suggested time period?

Dr. Richter:

Really great question. It depends upon the setting we’re looking at, and for the most part, a lot of people are probably asking about the maintenance setting. So, after initial therapy or after transplant, we put you on Revlimid. How long do we keep you on? The American adage has always been, “More is better,” so as long as you tolerate it and as long as it works. Outside of the U.S., they’ve done a couple of studies looking at one year and then stopping, or two years and then stopping.

And in a big trial that got presented a year or so ago, they compared the two years then stopping versus just staying on, and the people who just stay on do better.

So, now the current thinking is just keep you on long-term. What’s going to change that in the long term is we’re starting to use a technology called MRD, minimal residual disease, so, doing a marrow and trying to find one in a million or one in 10 million cancer cells.

And then, there’s something called sustained MRD meaning if you do two MRD analyses at least 12 months apart and they’re both negative, we call that sustained MRD negative.

And, there’s a hint that some people on maintenance Revlimid who have sustained their MRD negativity, they may do just as well stopping versus staying on it. We don’t know exactly who that is yet, but that’s going to be better understood in the next few years.

Katherine:

Okay. Randall writes, “I was diagnosed last year with myeloma, and my first treatment worked, but now I’ve relapsed. Is it too late to consider a second opinion or a consult with a specialist? Would that change anything?

Dr. Richter:

It’s a phenomenal question. There have actually been studies to show that if you engage with a myeloma center at least once within your myeloma journey, you do better than someone who has never done that. So, it is never a bad time to seek out a specialist. And one of the good things that came out of COVID is telemedicine. So, if there’s not someone right in your area, reaching out to some of our advocacy groups to help connect you to physicians like me or any of my colleagues, we’re more than happy to see anyone, I’ll see you with an MGUS that’ll never bother you, as will all of my colleagues and people who work in myeloma.

If you’ve had one prior line, 15 prior lines, anywhere in between. So, I think it’s always a good idea to see a specialist because he or she is more than happy to work with your local doctor to optimize your treatment without having to necessarily go to another center.

Katherine:

Yeah. Well, thank you for all of that, Dr. Richter. And, please continue to send in your questions to question@powerfulpatients.org and we’ll work to get them answered on future programs. So, Dr. Richter, we’ve talked a lot about why patients should play a role in their care.

What advice do you have for patients to help them feel confident in speaking up and becoming a partner in their care?

Dr. Richter: So, that’s not always easy for a lot of people to do, and for some people, no problem. They’ll speak up at the first sign of anything. One bit of advice I would give to people who may have concerns or may not feel as comfortable about doing this is first of all, there’s a lot of members of the care team. So, I have patients that may not want to mention it to me, but mention it to my nurse or the medical assistant, and we all talk. So, that’s one way.

The other thing that I think may help is involvement in patient support groups, hearing what others have to say about similar experiences and learning from them, them learning from you, and that may actually give you more of a confidence to speak with your care team. But, the advocacy groups like the MMRF and IMF have tons of local support groups where you can sit in, and specialists come and speak or people share stories. And I think that can be really helpful to figuring out your optimal journey.

Katherine:

And knowing that you’re not alone –

Dr. Richter:

Absolutely.

Katherine:

– in how you’re feeling. As we close out this conversation, I wanted to get your take on the future of myeloma. What makes you hopeful?

Dr. Richter:

So, we’ve had what we call Gestalt switches in myeloma. And what I mean by that is let’s rewind decades ago. We gave chemotherapy. Chemotherapy was designed to kill any cell that divides rapidly because that’s what cancer cells like to do.

It kills the good and the bad. It makes your hair fall out, throw up, horrible stuff. It doesn’t work too well. Then about 20 years ago, we started this switch to the novel therapies, Revlimid, thalidomide, Velcade, and then a decade later, daratumumab. And now, we’re having targeted agents which spend more time targeting the bad stuff, less time doing off-target stuff, really ramping things up.

We are at the precipice of a brand-new Gestalt switch in myeloma.

The immune world. The immune therapies. And right now, T-cell redirection therapy is what we call it either with CAR Ts, where we take your T cells out, engineer them, and put them back into your body all revved up, or we give you an off-the-shelf, bispecific that grabs onto your cancer and your T cell and, brace yourself, we even have trispecifics, which can engage your myeloma, another cell in your body, and yet another cell.

If you go on clinicaltrials.gov, which lists all the trials for everything, every disease, there are over 3,000 active trials in myeloma.

And what I tell people is when I first started and I sat across from a patient, I would say, “I’m really sorry. It’s not curable.” And now I say, “We are curing some people today by accident.” But over the next period of time, we’re going to do this deliberately and more frequently. And the goal is and always has been 100 percent of cure for 100 percent of patients, 100 percent of the time.

And, I kind of feel right now we’re almost like that 2001: A Space Odyssey when the obelisk lands. We have these immune therapies. We know they’re great. How do we combine them? How do we use them? How do we take all these great tools and turn it into a cure for everyone?”

And with so many great partners between advocacy groups and Pharma and patients and cancer centers, we’re going to collaborate and we’re going to start getting those answers in my lifetime, and I could not be more excited about that.

Katherine:

Oh, I bet. I bet. It seems like there’s been so much progress and hope in the field. Dr. Richter, thank you so much for joining us today. It’s been a pleasure.

Dr. Richter:

Thank you so much for having me. I’d love to come back anytime.

Katherine:

And thank you to all of our partners. To learn more about myeloma and to access tools to help you become a proactive patient, visit powerfulpatients.org. I’m Katherine Banwell. Thanks for joining us.

Updates in CAR T-Cell Therapy for Myeloma From ASH 2021

Updates in CAR T-Cell Therapy for Myeloma from ASH 2021 from Patient Empowerment Network on Vimeo.

Myeloma specialist, Dr. Omar Nadeem, shares the latest updates in CAR T-cell therapy from the 2021 American Society of Hematology (ASH) annual meeting. Dr. Nadeem discusses long-term study results and optimism for the future of CAR T-cell therapy.

Dr. Omar Nadeem is the Clinical Director of Myeloma Cellular Therapies Program and Director of Myeloma and Plasma Cell Pathways at the Dana-Farber Cancer Institute. Learn more about Dr. Nadeem, here.

See More from Thrive Myeloma


Related Programs:

The Latest in Myeloma Research: Updates from ASH 2021

The Latest in Myeloma Research: Updates from ASH 2021

How Could Clinical Trials Fit Into Your Myeloma Treatment Plan?

How Could Clinical Trials Fit Into Your Myeloma Treatment Plan?

An Expert’s Hopeful Outlook on Myeloma Research and Treatment

An Expert’s Hopeful Outlook on Myeloma Research and Treatment 


Transcript:

Dr. Nadeem:

My name is Omar Nadeem, and I’m at the Dana Farber Cancer Institute in Boston, Massachusetts. I’m an instructor of medicine at Harvard Medical School, and I direct the myeloma cellular therapies program at Dana Farber.

Katherine:

Dr. Nadeem, you’ve joined us from the American Society of Hematology Meeting in Atlanta. Can you share any highlights in myeloma from the meeting?

Dr. Nadeem:

Yeah, it’s a very exciting time in myeloma therapeutics. We’re seeing a lot of new agents that are being reported at this meeting, showing very promising results.

Then we’re also fine tuning the way we treat myeloma patients by looking at different combinations in all lines of therapy, whether it be front-line or relapsed setting, to try to really understand which treatments are the best and then also more importantly, which treatments do we need to continue patients on, etcetera as they’re going through their myeloma journey. So, lots of updates with important trials at this meeting so far.

Katherine:

We’re hearing a lot about the promise of CAR T-cell therapy. Is there any research news in CAR T-cell for myeloma treatment?

Dr. Nadeem:

Yeah. So, we’ll have a presentation later today, actually, updated results of the CARTITUDE-1 study, which is looking at cilta-cel, which is an anti-BCMA directed CAR-T cell product.

And this trial is a phase-1/2 study looking at some patients with relapse in refractory multiple myeloma that has been reported previously to have a very, very high response rate and very high rates of MRD negativity.

So at this meeting, with just longer follow-up, which is what we’re looking for in terms of how long these responses last, we’re starting to see that the median duration of response is now almost 22 months, which is very impressive looking at the data and comparing it to some of the other CAR-T products that are either under study or the one that’s currently approved.

So, that looks very promising. And also notably, we had some concerns initially about toxicity with this particular product. But that really hasn’t been seen with longer follow-up. So, we’re not seeing a toxicity signal, particularly as it relates to neurological toxicity, with the longer follow-up. So, that presentation will be later today. We look forward to seeing the updates, but so far this looks very encouraging and this is what we anticipate to be the next product that’s available in the market for myeloma.