Advancements and Challenges in Treating Relapsed/Refractory Multiple Myeloma

In part 1 of an interview, Suzanne Lentzsch, MD, PhD, director of the multiple myeloma and amyloidosis program and professor of medicine at Columbia University's College of Physicians and Surgeon, spoke with The American Journal of Managed Care^® (AJMC^®) about new data on linvolseltamab, a B-cell maturation antigen and CD3 bispecific antibody that is under investigation as a treatment for relapsed/refractory (R/R) multiple myeloma. Lentzsch presented these data in the abstract, “Linvoseltamab in patients with R/R multiple myeloma in the LINKER-MM1 study: depth and durability of response at 14-month median follow-up,” at the recent European Hematology Association 2024 Congress.

Here she continues the discussion by touching on potential new treatments for R/R multiple myeloma, important clinical considerations when choosing optimal therapy for patients with this hematologic cancer, and clinical challenges that continue to put up roadblocks to effective patient treatment.

AJMC: Can you discuss new therapies under development for the treatment of patients with R/R multiple myeloma?

Lentzsch: There are many new developments in relapsed/refractory multiple myeloma. We recently had an approval of 2 chimeric antigen receptor [CAR] T cells for earlier lines of treatment: idecabtagene vicleucel (Abecma; Bristol Myers Suibb) and ciltacabtagene autoleucel (Carvykti; Janssen/Johnson & Johnson)—cilta-cel and ide-cel. Those treatments are approved for the first line of treatment, and right now we have the ability to use them for the first relapse [with] cilta-cel and ide-cel for the second relapse. I would say that brings our armamentarium of immunotherapy for relapsed/refractory patient to a much earlier line of treatment.

Right now, we also have 2 approved bispecific antibodies, the BCMA bispecific antibodies teclistamab and amivantamab. And we have talquetamab, a GPRC5D bispecific antibody. Those are approved, but we have 2 more in development: linvoseltamab from Regeneron, and another one from AbbVie that doesn't have a name, only a number, ABBV-383.

AJMC: What factors should clinicians consider when selecting a therapeutic for treating a patient with R/R multiple myeloma?

Lentzsch: The sequencing of the treatment for [patients who have relapsed/refractory multiple myeloma] is not 100% clear. But we know that patients can undergo severe cytokine release syndrome [CRS] receiving CAR T cells. So in my opinion, I think that we should really focus more on the fit patient, maybe transplant eligible, then we consider CAR T cells. Bispecific treatments might be more for patients who are frail and older, and especially belantamab is very well tolerated. It has a very low grade of CRS or ICANS [immune effector cell–associated neurotoxicity syndrome]. And maybe belantamab in combination was pomalidomide is an excellent treatment for the very frail patient population. The downside is that it has ocular toxicity, which limits really the application for patients who need their vision.

AJMC: What clinical challenges remain when treating these patients, and what strategies could address these challenges?

Lentzsch: We still face many challenges when we treat our [patients who have relapsed/refractory disease]. One challenge is that we have right now 3 different approaches to target the BCMA-expressing multiple myeloma cells: CAR T cells, bispecifics, and the antibody-drug belantamab. The question is, can we use one drug after the other? Or do we exclude using CAR T cells targeting BCMA after we use the BCMA bispecific amivantamab?

Those are really questions we have to answer. The good news is that we have talquetamab, I mentioned already; that is a GPRC5D antibody that has a different target. So maybe after the BCMA targeting therapy, we might switch to a GPRC5D bispecific antibody or CAR T cell that's also currently in development.