The Evolving Role of Non-BCMA-Targeting Bispecifics in Multiple Myeloma
Following their review of non-BCMA-targeting bispecifics in multiple myeloma, panelists consider practical use of these agents and how they may fit into the real-world treatment paradigm.
Transcript:
Amrita Krishnan, MD:Thank you all for some great presentations. We keep coming back to the same question, and I sympathize with physicians in the community who are somewhat frustrated with myeloma because there are so many agents and no clear path to choose. Let’s be a little broad, are people going to pick a non-BCMA–targeting agent first and save BCMA for later, or how are you going to do it?
Alfred Garfall, MD:To calm the nerves of the community physicians, when you get myeloma doctors together, they will split hairs about different sequences. The most important thing for our patients is that they have a chance at all these therapies at some point. These are new tools in the toolkit, and the history of myeloma is longer survival with more therapies available. While everybody will have their preference, I don’t think people have to stress too much at this point, where all the data we have are very anecdotal and small scale about which one to choose first. You can be driven by logistical issues, patient preferences, as long as patients have a chance at all the effective therapies at some point. To answer your question Amrita, I’m not sure. I think it will depend on how the clinical trials come out and in which settings these get FDA approved or approved in different jurisdictions. That will probably drive, for me at least, some of the decisions in the early going.
Amrita Krishnan, MD:Let me be even more specific then, and Josh made some nice points, the infection rate is lower with non-BCMA–targeting agents. But let’s talk about talquetamab and some of the unique toxicities in regard to the dysgeusia in about 60% of people.
Philippe Moreau, MD: It will be good to have more agents available, but for the optimal sequence, we need more data. I would like to do, if I had those agents available, is use cilta-cel [ciltacabtagene autoleucel] first because I believe that this CAR [chimeric antigen receptor] T-cell therapy is amazing. Then at the time of the progression, maybe a change of target with talquetamab or targeting GPRC5D. With the issue of this specific toxicity, it’s true that we sometimes have to decrease the talquetamab or delay the dose, and the dysgeusia will disappear. Why? We don’t know exactly, but with the subsequent administration, that’s not a big issue. This is what I would like to do, but we need more data for sure.
Amrita Krishnan, MD:I think Josh you mentioned forimtamig. I looked at that abstract. I thought it was interesting they didn’t mention a lot of dysgeusia. I don’t know if it’s because they haven’t reached a dose that’s high enough yet.
Josh Richter, MD: That’s I think a fair point. Also we’re looking at GPRC5D as a CAR T target, and we’re not seeing tons of those same issues as well. I don’t think the book has completely been written on this AE [adverse effect]. I think it’s been said many times, we just need more data to answer this.
Amrita Krishnan, MD:Philippe makes a good point about dose schedule changes being the biggest thing to keep people on therapy once this drug gets approved.
Sandy Wong, MD: In terms of forimtamig, I was surprised. I was sitting right up at the screen when it was being presented and when I got a copy of the slides, on the bottom right in very fine print it lists…. What they did, they wound up grouping a lot of those symptoms under mucosal toxicity or something along those lines. I think they did probably have some of those toxicities since it was listed there, but it’s not clear because it got all lumped together, how much it was. I agree with my copresenters that I think in the AE table for talquetamab you see the all grade, which is just grade 1 and 2, for the…definition. But grade 2 can be miserable for patients because it includes not just a loss in their taste buds, but patients who say everything tastes rotten, and that is a powerful statement. I’ve had patients who have said they no longer drink wine because it tastes horrible.
Quality of life is important to think about. You’re absolutely right, when it comes to reducing the dose or even the frequency of dosing, those symptoms become much more manageable. To add to the sequencing paradigm, I like that paradigm too, and perhaps you could do cilta-cel, then talquetamab, then maybe even cevostamab, and then teclistamab because then you give some time between 2 BCMA-targeted agents. This is all hypothesizing, but we definitely need more studies.
Transcript edited for clarity.
