Understanding Myeloma Therapy Targets BCMA and GPRC5D

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Understanding Myeloma Therapy Targets BCMA and GPRC5D from Patient Empowerment Network on Vimeo.

What are myeloma targets, and how do they impact the effectiveness of therapy? Dr. Krina Patel explains how treatments like bispecific antibodies and CAR T-cell therapy are using myeloma targets such as BCMA (B-cell maturation antigen) and GPRC5D (G protein-coupled receptor 5D) to kill myeloma cells. 

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.

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Will CAR T-Cell Therapy Be Approved for Earlier Lines of Myeloma Treatment

Will CAR T-Cell Therapy Be Approved for Earlier Lines of Myeloma Treatment?

 How Is CAR T-Cell Therapy Research Advancing Myeloma Care?

How Is CAR T-Cell Therapy Research Advancing Myeloma Care?

 How Can Myeloma Patients Access CAR T-Cell Therapy Clinical Trials?

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Transcript:

Katherine:

We know that the currently approved bispecific antibody therapies target BCMA and GPRC5D. What are these targets precisely and how do they impact the effectiveness of the treatment? 

Dr. Krina Patel:

No, it’s a great question.  

And, again, so BCMA we’ve had for a little bit longer.  

We’ve known about it for a little bit longer, B cell maturation antigen, which definitely we’ve used as much as we can. So, we’ve had CAR Ts for it. We’ve had bispecifics for it. We’ve had antibody drug conjugates that we’ve attached to it. 

So, it’s a really good target that is mostly just on myeloma cells and on very few other cells in the body, for the most part, which is why it makes such a great target. The side effects really should happen only specifically against the myeloma; so, less side effects in terms of toxicity. That’s not 100 percent the case.  

BCMA is in some other tissues, like maybe the nerves, and that’s why maybe we see this toxicity sometimes, potentially in the GI system. Some patients can have it in other places. If you have myeloma in, let’s say, areas like the kidney. If you have a plasmacytoma, it can go to the kidney, things like that.  

But again, for the most part, mostly on myeloma. And what’s really important about these targets is, once you get a treatment for it, what happens to that target. So, that’s a little bit different between these two targets. So, BCMA is a part of the proliferation of myeloma cells. So, it actually helps the myeloma cell survive. And so, the myeloma cells really want that BCMA on there. Now, for CAR T, for the most part, we don’t see people losing BCMA. We might see it go down in the myeloma cells that are left. For some patients, the expression can go down. But for the most part, we’ll see it come back up a few months later if the myeloma’s coming back.  

The way that resistance happens with BCMA is that, when people are on bispecifics, the other treatment, we can sometimes see the BCMA get mutated. And then, maybe the other therapies we have won’t go after it any more.  

So, again, it’s not common, but that’s sorta something we look at when we talk about sequencing therapy or which therapy should we use first. Then, GPRC5D’s a little different.  

So, again, mostly just on myeloma cells. But here, we do know it’s on something called epithelial cells, which is skin, nails, tongue. And that’s why some of the side effects that we see, especially with the bispecific that’s a standard of care already, talquetamab, is skin and nail changes. So, people can get sloughing of their hands and nails; that can get disrupted. And then, taste. People can actually have some significant taste loss, to the point that they can have weight loss from it.  

So, this is why that part is so important that if we have patients with these side effects, we need to hold the drug or decrease it; so, make sure we can turn those around. And then, the way GPRC5D is we think that it’s a little bit more likely that you can lose it once you get a treatment with GPRC5D that the myeloma can actually learn how to shed the antigen.  

So, again, this really becomes important when we talk about combination and sequencing of all these different therapies we have and what’s the best way to do it so that patients can have the best response and the longest response.

How Is CAR T-Cell Therapy Research Advancing Myeloma Care?

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How Is CAR T-Cell Therapy Research Advancing Myeloma Care? from Patient Empowerment Network on Vimeo.

What progress is being made in furthering advancing CAR T-cell therapy for myeloma? Dr. Krina Patel discusses the manufacturing process for CAR T-cells, research updates for manufacturing CAR T-cells faster, and the benefits of bridging therapy for some patients. 

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.

Related Resources:

How Can Myeloma Patients Access CAR T-Cell Therapy Clinical Trials?

How Can Myeloma Patients Access CAR T-Cell Therapy Clinical Trials?

 Will CAR T-Cell Therapy Be Approved for Earlier Lines of Myeloma Treatment

Will CAR T-Cell Therapy Be Approved for Earlier Lines of Myeloma Treatment?

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Advances in Managing CAR T-Cell Therapy Side Effects

Transcript:

Katherine:

Are there other advances in CAR T-cell therapy that patients should know about?  

Dr. Krina Patel:

Yeah, so I think part of the issue right now is manufacturing and how long it takes for patients to get those cells. So, we use it to our advantage in the sense that earlier-line patients will have bridging therapy that we can give them while we’ve collected their cells and they’re being made; it takes are 4 to 6 weeks, or even eight weeks sometimes that we can give them a therapy that can knock their myeloma down before they get the CAR T.  

And again, this is really important that we have options available. So, in fifth-line we don’t have very many options available. So, a lot of my patients, we really are just struggling to keep the myeloma controlled, try to bring it down before they get their CAR T. We’re hoping that that CAR T comes in any day.  

When it goes earlier, I’m hopeful that now we’ll have options to actually bridge patients better because we’ll have more therapies they haven’t had. And the reason that bridging is so important is it really does decrease toxicity, some of the serious toxicity with see with CAR T; significantly decreases it.

And the efficacy. We see patients will do much better for longer if they have less myeloma going in than lot of myeloma going in. And so, again, I think because of that time, if we could get those cells earlier, that just makes it so much easier for all our patients to make sure that they’re able to get the cells. So, there’s quite a few different trials looking at fast CAR T production.  

And so, there’s the PH383, I think. I can’t remember the number exactly. But this is one of the studies that was happening at Dana-Farber, and Dr. Sperling has presented couple time. The cells are made within just 24, 48 hours. And then, they actually go in and as they’re killing the myeloma, they grow.  

So, they grow inside the body which is really, really, I think, a interesting way to develop CAR Ts for the future, make it more applicable and accessible. And then, there’s other companies in China. There’s the FasT CAR, which is a CD-19 plus BCMA, so two targets. But again, they can make their CAR Ts within a week.

And in the end, you have to still do quality checks for the FDA, which still take two weeks. So, it always will still be a few weeks, but still, the faster you can make those CAR’s, the more likely our patients are gonna be able to get it. And then, I think the combination studies. Again, there’s gonna be studies with different targets. So, there’s two CAR Ts, again, GPRC5D, that are going to be tested in the U.S.  

A phase two study. And then, also another phase one study. And then, the phase two study, that GPRC5D CAR T is going to have combination studies coming out very, very soon. Actually, it’s already open in some places, and more places that are opening soon.  

So, I think, yes, a lot’s going on again with new antigens and combinations. 

How Can Myeloma Patients Access CAR T-Cell Therapy Clinical Trials?

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How Can Myeloma Patients Access CAR T-Cell Therapy Clinical Trials? from Patient Empowerment Network on Vimeo.

How can patients learn more about joining myeloma CAR T-cell therapy clinical trials? Dr. Krina Patel shares advice for identify and accessing these trials, noting that seeking care with a myeloma specialist can be most helpful. 

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.

Related Resources:

Will CAR T-Cell Therapy Be Approved for Earlier Lines of Myeloma Treatment

Will CAR T-Cell Therapy Be Approved for Earlier Lines of Myeloma Treatment?

 How Is CAR T-Cell Therapy Research Advancing Myeloma Care?

How Is CAR T-Cell Therapy Research Advancing Myeloma Care?

 Understanding Myeloma Therapy Targets BCMA and GPRC5D

Understanding Myeloma Therapy Targets BCMA and GPRC5D

Transcript:

Katherine:

How can patients find and access clinical trials that are looking at CAR T-cell as an earlier line of therapy?  

Dr. Krina Patel:

That’s a great question. So, I think going to any place that is myeloma specific. So, basically a big center that has doctors that are doing myeloma research, they will be able to definitely get you into places that have some of these trials. But clinicaltrials.gov is one other place. It’s really hard. I will tell you that, if I wasn’t a physician or in medicine, I don’t think I would learn, I would be able to navigate it very well.  

And so, really either through your doctor and having them look this up for you, or going to patient groups. So, again, a lot of my patients are part of different patient groups where people will say, “Well, this is a trial that I was” or “This is a trial that my doctor told me about.” And then, asking. So, that’s the other big thing is constantly asking your doctor “What are my other options?” getting second opinions from myeloma experts, and then just paying attention to some of these resources that you have available. Right now, there are gonna be more clinical trials for earlier-line therapies and first-line with both cilta-cel and ide-cel.  

There’s going to be clinical trials with new products: ddBCMA CAR T, that is likely gonna come out soon for earlier-line therapies. And so, there’s a lot happening, and so there might be different clinical trials in different places. But I think the fact that all this is going on at once is really important for our patients to know about. 

Will CAR T-Cell Therapy Be Approved for Earlier Lines of Myeloma Treatment?

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Will CAR T-Cell Therapy Be Approved for Earlier Lines of Myeloma Treatment? from Patient Empowerment Network on Vimeo.

Is there an opportunity for myeloma patients to gain access to CAR T-cell therapy sooner? Dr. Krina Patel discusses the results of clinical studies for CAR T-cell therapy and the potential for patients receiving the treatment earlier in their myeloma journey.

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.

Related Resources:

How Can Myeloma Patients Access CAR T-Cell Therapy Clinical Trials?

How Can Myeloma Patients Access CAR T-Cell Therapy Clinical Trials?

 How Is CAR T-Cell Therapy Research Advancing Myeloma Care?

How Is CAR T-Cell Therapy Research Advancing Myeloma Care?

 Advances in Managing CAR T-Cell Therapy Side Effects

Advances in Managing CAR T-Cell Therapy Side Effects

Transcript:

Katherine:

Dr. Patel, current CAR T-cell therapy is FDA approved for patients who have had several lines of treatment. 

But we know that there are a number of trials that are exploring this treatment in earlier lines. So, what is the progress on these trials? 

Dr. Krina Patel:

Yeah. So, I think we have two major ones that have already been done and we’ve heard the results from. So, CARTITUDE-4 was for cilta-cel in second to fourth-line; so, patients who have relapsed once, all the way up to three times.  

And then, KarMMa-3, which is ide-cel, which was one line later. So, that was third-line to fifth-lines; so, relapsed twice to four times. So, little bit different patient populations in the two trials. The trials were different in that patients had different therapies before too.  

But both were positive studies which was what was really exciting. So, in CARTITUDE-4 patients were randomized, meaning they got either the CAR T or they got a standard of care option. And the CAR T won by a lot. This was, we call, hazard ratios.  

But basically, the amount of different of patients surviving when they got CAR T without myeloma versus the standard of care was one of the biggest differences we’ve ever seen in a clinical trial for multiple myeloma. So, it’s – 

Katherine:

Wow. 

Dr. Krina Patel:

– something really pretty amazing. And then, KarMMa-3, that trial, same thing. There’s a huge difference in the patients who got CAR T versus the standard of care. The standard of care options were different in the two trials for the most part. So, again, different patient populations and different standard of care options, but the other big thing that the KarMMa-3 study did was they allowed for patients who are on the standard of care that, once they were relapsing, they could get the CAR T.  

And so, because we have this crossover the big controversial thing that came up was, “Well, patients aren’t necessarily living longer by getting CAR T earlier. As long as they get CAR T they do really well.” And so, that is why there was a big meeting with the FDA what we call the ODAC meeting.  

So, they had both companies present their trials to the FDA and to this advisory board that they had called ODAC, and thankfully it was positive. So, both studies were positive in terms of the advisory board saying that they agreed these should be moved up forward.  

So, now we’re just waiting and hoping the FDA approves them so that we can actually give it to patients. I think the biggest reason is access. So, we know that when patients are fifth-line, which is when it’s approved now, not everybody makes it to fifth-line. It’s really hard to get through all these therapies and then still be healthy enough to do this versus if it’s approved in second and third-line, that just means so many people can actually get these therapies and available to them.  

And the other big thing is the quality-of-life piece for CAR T. It’s been such a big difference when patients get a break from therapy for a year or two years or longer compared to being on continuous therapy. And so, both studies have had quality of life studies come out as well showing that difference between the standard of care versus the CAR T.