Addressing Toxicities of BCMA-Targeted Therapy for Multiple Myeloma

Adam Cohen, MD, director of myeloma immunotherapy at Penn Medicine and associate professor of medicine at the Hospital of the University of Pennsylvania, discusses the adverse events (AEs) of concern associated with B-cell maturation antigen (BCMA)-targeted therapies for relapsed/refractory multiple myeloma (R/R MM) at the Summit of the Americas on Immunotherapies in Hematologic Malignancies, hosted by Miami Cancer Institute.

BCMA-targeted therapies approved for use in R/R MM include belantamab mafodotin (Blenrep) and the chimeric antigen receptor (CAR) T-cell therapies ciltacabtagene autoleucel (cilta-cel; Carvykti) and idecabtagene vicleucel (ide-cel; Abecma).

Cohen says that for cilta-cel and ide-cel, like other CAR T-cell therapies, cytokine release syndrome and neurotoxicity are serious AEs for some patients. They typically occur in the first week of treatment and patients may need to be hospitalized during CAR T-cell infusion or within a few days to monitor their safety post treatment. They can be managed with supportive care including steroids and tocilizumab (Actemra).

Additionally, he says BCMA-targeted therapies can be significantly immunosuppressive due to hypogammaglobulinemia and increased risk of infections, and these AEs can persist for months during or following treatment. Physicians should monitor patients closely for signs of infection. They can manage these issues with intravenous immunoglobin (IVIG) replacement and prophylactic antimicrobials.

TRANSCRIPTION:

0:08 | CAR T-cell products, the main risks with those are similar to CAR T cells for other diseases, namely cytokine release syndrome and neurotoxicity. This tends to occur within the first week of treatment. Patients are typically hospitalized either during the CAR infusion, or shortly thereafter for monitoring for this. We've learned how to really manage these with aggressive supportive care, and in some cases, tocilizumab or steroids to try to minimize the risk of these becoming severe. That's something we definitely need to keep an eye out for with the CAR T-cell products, at least in the immediate post-treatment period.

Later on, I think the key thing that we're learning is that these certainly can be very immune suppressive. Targeting BCMA can lead to hypogammaglobulinemia and increased risk of infections that can persist for months. These patients often need IVIG replacement, they need to be monitored closely with prophylactic antimicrobials as needed, and prompt treatment of any signs of infection.