What Is the Role of BCMA-Targeted CAR-Ts in Late-Relapse Multiple Myeloma?

A roundtable discussion, moderated by Saad Usmani, MD, of Memorial Sloan Kettering Cancer Center, focused on treatment considerations for relapsed or refractory multiple myeloma, including updated data from the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. Dr. Usmani was joined by a panel that included Yi Lin, MD; Shambavi Richard, MD; and Meera Mohan, MD.

In this segment of the roundtable series, the panel discusses the US Food and Drug Administration (FDA)-approved BCMA-directed chimeric antigen receptor T cell (CAR-T) options for multiple myeloma, including data from KarMMa-3 and CARTITUDE-4.

Watch the next segment in this roundtable series.

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Dr. Usmani: In late-relapse patients who are triple-class exposed or refractory, we have three BCMA-targeting treatments that are currently [FDA] approved. But we now have data with the KarMMa-3 trial, and the CARTITUDE-4 study is also going to be presented at ASCO, or has been presented at the ASCO meetings. Can you tell us a little bit about both of those trials and what the patient populations were?

Dr. Mohan: The KarMMa-3 study, as we know, is a phase III randomized study of patients who’ve got two to four prior lines of therapy. The patients were randomized to idecabtagene vicleucel (ide-cel) versus physician’s choice, which in the study was mainly a daratumumab-based regimen and there were also some doublet regimens as well.

We saw a progression-free survival (PFS) of about 13 months with ide-cel and the hazard ratio was about 0.49. These are impressive results, given the tough, high-risk population. These are patients who have early relapse, which is functionally high risk and it’ll be really exciting to see the CARTITUDE-4 results. Again, similar patient population, phase III study randomizing patients who have got one to three lines of therapy to ciltacabtagene autoleucel (cilta-cel), versus DPd (daratumumab, pomalidomide, dexamethasone), or lenalidomide with pomalidomide and dexamethasone.

Dr. Usmani: I agree with you. I think that there’s a lot of excitement, and one thing that I want to make sure that we distinguish is, the lines of treatment were different across these two studies. But in terms of inclusion criteria, I think there were some differences as well. I think with CARTITUDE, patients who had prior daratumumab exposure or refractory-ness were not allowed on the study, because the standard-of-care arm essentially was daratumumab-based triplets, whereas it was different for the KarMMa-3 study. In KarMMa-3, the PFS that we see, at least ide-cel is consistent. We are seeing the same PFS in late versus this study. But what are your thoughts about that?

Dr. Lin: That’s a great point that you raised. Now I think a lot of us in the myeloma community have been talking about [this], it was very important for us to define lines of therapy, what we consider as new line of therapy. But now in the current treatment era, we use combinations already upfront. By the time the patient has relapsed, it’s not a matter of how many lines, it’s what are they refractory to already. I think that’s what we’re seeing with the KarMMa-3 results. Everybody was hoping, “Oh, well, the patients on KarMMa-1 had a median of six prior lines of therapies; on this study it’s three or four. That’s many lines earlier, and hopefully their T cells are less beat up, they’re more fit. Should we be expecting to see maybe a longer PFS than what we saw in KarMMa-1, as much as we can, or can’t, compare across studies?”

What we are really seeing is that there’s still a good percent of those patients in KarMMa-3 that were triple-penta-exposed and then still a smaller percent, but some percent of patients, who are refractory. With that type of patient demographics, it is probably not as surprising. It’s actually reassuring that the PFS at least held in another study, in a randomized controlled study. I think what we will really find out is where CAR-T gets studied in a frontline setting where patients are only exposed, let’s say to induction therapy, and they’re just coming into active myeloma. Does CAR-T perform differently there versus later lines?