Real-World Use of BCMA-Targeted Therapy in Myeloma

Transcript: Ajai Chari, MD: I think my main interest, these are all amazing, and BCMA [B-cell maturation antigen] is such a hot target. One big unmet need is the sequencing of days, like if you get one I think my main interest in thinking about this, especially for the community person who might be watching, is how might these translate to the real world? Each has its issues. CAR [chimeric antigen receptor] T-cell therapy, there’s tremendous selection bias in who’s even getting a slot because it’s very competitive. Then of those who signed consent, we pick within our institutions the best patients, and then of those who get leukapheresis, how many get to the actual infusion and get the product made? What’s the impact of the bridging chemotherapy on the PFS [progression-free survival], and then the CRS [cytokine release syndrome]? We’re essentially picking transplant-eligible patients. These aren’t fragile elderly patients, so the CRS grade 2 might be very difficult in an older patient, with a vasculopath. That’s the challenge with CAR T, but clearly a 1 time intervention for patients is amazing, right? Although we say 1 time, but there’s frequent cytopenia, supportive care visits as an outpatient.

The ADC [antibody-drug conjugate], super easy to give but then the ocular monitoring and remembering that there’s exclusion criteria for who gets into the study at baseline. You can’t have bad disease, ocular issues to start with. Then it required certain monitoring, so how would that deploy in the clinic and what would be the real-world ocular findings and management? Then that leaves me with, probably if I had to put money on it, I would put the BiTEs [bispecific T-cell engagers] because I think the issue there is, yes, there is CRS, but there’s step-up dosing, early use of TOCI [tocilizumab], changing all of these things. Most likely I guess the first cycle probably will be still done in academics, but after that, when you’ve gotten through the risk of CRS, I think it’s easily deliverable in the community without any ocular monitoring. If we don’t allow sequencing, I would say that’s probably for the typical relapsed patient with multiple comorbidities, that would be my guess.

Sagar Lonial, MD, FACP: I think what was not heavily represented here is if you’ve gone through IMiDs [immunomodulatory drugs], PIs [proteasome inhibitors], CD38, and you’re ending up with some sort of BCMA-targeted approach, that now we’ve got new IMiDs that may partner even better with those drugs.

Paul Richardson, MD: Both Sagar and I were part of earlier meetings with both CC-220, iberdomide, and of course, CC-480, which are very exciting. I will make 1 qualification. I do have, and I think Sagar and I both feel the same on this, we do have a lot of faith in the possibility for the ADC.

This ocular toxicity, I think it’s obviously a concern but we must not overstate it because essentially, especially in combination and especially if you can bring down dose; it all comes from the auristatin warhead. It’s not got anything to do with BCMA. I think we can manage that because from an off-the-shelf point of view, that will have real merit.

Ajai Chari, MD: I think the issue is going to be sequencing, right? You’re only going to get 1 shot.

Paul Richardson, MD: I’ve got you. And that’s a great question because obviously it may be that you can try a cellular approach first, and then if that fails, you can target with a recapture using an ADC.

Sagar Lonial, MD, FACP: Yes, because I don’t know that you’re only going to get 1 shot.

Paul G. Richardson, MD: Exactly, I was going to say.

Ajai Chari, MD: Not for a while though, right?

Paul Richardson, MD: I think that is a perfect spot because as we think about the relapsed/refractory space, we’ve covered it remarkably well. I do think especially with our panel and not least, Ajai, that it’s important to acknowledge that beyond BCMA in the relapsed/refractory space, we have important other drugs, not least of which is selinexor. We also have already approved drugs like panobinostat, and all of these drugs actually do provide salvage strategies. I think in terms of selinexor, there were data at the meeting, wasn’t there, about not only successful partnering with pomalidomide, but most importantly, there was successful activity in patients in whom CAR T had failed.

I think there are important data there. We also presented data, and Amrita will smile, on the melflufen, which continues to show its promise as a powerful peptidase activated cytotoxic. I think that basically we’ve got lots of other options for our patients beyond that. I wanted to finish by asking everyone for a quick 45 second sound bite as it were on their thoughts. If I may, Sagar, if I could start with you very quickly.

Sagar Lonial, MD, FACP: I think it was an exciting meeting. We have the beginnings of precision medicine in myeloma with the translocation 11;14 subsets. We have effective induction therapies with the addition of immunotherapy, and then we have great salvages coming with immune therapy as well. I think for us it’s really fun and exciting. The reality is it makes a big difference for patients and patient outcomes, and that’s what’s so exciting.

Paul Richardson, MD: Very well said. Ken.

Kenneth H. Shain, MD, PhD: To echo Sagar, it’s essentially the same thing. It’s been a great meeting. We have new ways. We’re opening the door to all these cellular therapies, whether it be BiTE, bispecific, CAR T. We’re just at the very beginning of how we can utilize those in the context of our patients. We have new drugs that hopefully get put out to the community. We have to remember that still the community physicians need therapies for our patients. These are all myeloma patients, and so the more we have the better off we’re going to be. I think all that falls into the context of a theme we’ve all talked about, how can we individualize our therapy, how do we utilize the right drugs for the right patient at the right time? I think these are all new ways to do it. We have to figure out a better way of doing it.

Paul Richardson, MD: Nina.

Nina Shah, MD: Yes, I thought the data this year were great. Immunotherapy, not always to combine things. Particularly the biomarker-based venetoclax therapy I think was exciting, and most importantly that we looked at elderly, unfit, frail patients, also quality of life outcomes. I think that was great.

Paul Richardson, MD: Lovely. Amrita.

Amrita Krishnan, MD: I think to me the exciting thing is having new classes of drugs now. I already mentioned it earlier, but the bispecific T-cell engagers to me are now really moving into more prime-time space.

Ajai Chari, MD: I guess I’ll continue with my movie theme, which is I think we’re getting closer to basically creating a home movie that’s personalized high-definition, both in the smoldering and once patients become symptomatic. You really can’t do 1-size-fits-all. It depends on what therapies, patient, disease, and treatment factors. It’s nice to have an arsenal of drugs to be able to help make that movie.

Paul Richardson, MD: I love your movie thought, I think it also dovetails to the concept that treating myeloma is not tactical, it’s truly strategic, and fortunately we’re in that position to do it now. Thank you very much. Thank you so much for your contributions to our discussion. On behalf of the panel, we want to thank our audience for joining us. We hope you found this Peer Exchange discussion to be useful and informative. We much appreciate your kind attention.

Transcript Edited for Clarity