Dr Kin on the Limitations of BCMA-Targeted Therapies in Myeloma

Andrew Kin, MD, medical oncologist, Karmanos Cancer Institute, discusses the limitations and unmet needs associated with the use of BCMA-targeted therapies in relapsed/refractory multiple myeloma.

The BCMA-directed CAR T-cell therapies ciltacabtagene autoleucel (cilta-cel; Carvykti) and idecabtagene vicleucel (ide-cel; Abecma), as well as the BCMA/CD3-targeted bispecific antibody teclistamab-cqyv (Tecvayli), are all approved by the FDA for the treatment of patients with relapsed or refractory multiple myeloma who have received at least 4 previous lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. However, not every patient in this setting is going to be a candidate for BCMA-targeted therapy, Kin begins. These 3 BCMA-targeted agents are high-intensity regimens that are associated with adverse effects such as cytokine release syndrome (CRS), which require close monitoring during these treatments, Kin explains.

The BCMA-targeted antibody-drug conjugate belantamab mafodotin-blmf (Blenrep) previously held accelerated approval for patients with relapsed/refractory multiple myeloma; however, GlaxoSmithKline plc initiated the process to withdraw the United States marketing authorization for the ADC within this space, based on results from the phase 3 DREAMM-3 trial (NCT04162210), which did not meet its primary end point of progression-free survival for belantamab mafodotin compared with pomalidomide (Pomalyst) plus low-dose dexamethasone. Belantamab mafodotin is under exploration in other clinical trials in multiple myeloma with the hope that it will gain reapproval, which could represent another BCMA-targeted therapy that is not associated with CRS, Kin adds.

Although BCMA-targeted therapies can produce responses, response rates could drop for patients who have had exposure to a prior BCMA-targeted therapy, Kin says. Developing other bispecific antibodies, CAR T-cell therapies, and other agents with different targets outside BCMA could provide other treatment options after BCMA-targeted therapy, Kin concludes.