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Improving Response Durability of Myeloma Immunotherapies

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Published on March 30, 2020

Key Takeaways

  • Studies like CARTITUDE and KarMMa-1 are looking at how long CAR T-cell therapy keeps patients from progressing and that getting the right dose is key.
  • Trials are also looking at using CAR T as second- and third-line treatments, combining it with other drugs and how to sequence therapies.
  • There are many immunotherapies available. Talk with your doctor about what could work best for your type and stage of myeloma.

Chimeric antigen receptor (CAR) T-cell therapy is a hot topic in the myeloma world. Some patients respond well to this type of treatment while others do not, so researchers are working to improve the response durability. 

A panel of experts, including Dr. Nina Shah, Dr. Faith Davies and Dr. Larry Anderson, give updates on where CAR T is today from data presented at a recent conference.  

Watch as they cover information on response rates, managing toxicity and who this type of treatment is best suited for. You will also learn about the variety of immunotherapy options available today.

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

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NYU Langone's Perlmutter Cancer Center

Transcript | Improving Response Durability of Myeloma Immunotherapies

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

Jenny Ahlstrom:                           

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

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

What are you seeing in CAR-T cells, it seems like the initial data came out a few years ago and we’re seeing people respond in really great ways? Maybe not so durable. And now strategies are coming into play as to actually improve the durability. So, what are you seeing in the area of CAR T first?

Dr. Shah:                      

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

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

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

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

Dr. Anderson:               

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

Dr. Davies:                    

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

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

Dr. Shah:                      

...20 months, PFS 20 months.

Dr. Davies:                    

The time that patients stayed in remission for.

Jenny Ahlstrom:                          

So, you’re almost doubling there.

Dr. Davies:                    

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

Jenny Ahlstrom:          

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

Dr. Anderson:               

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

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

Dr. Davies:                    

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

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

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

Dr. Anderson:               

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

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

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

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