Dr Berdeja on the Current Landscape of BCMA-Directed Therapies in Multiple Myeloma

Jesus Berdeja, MD, director, Multiple Myeloma Research, Tennessee Oncology, discusses the BCMA-directed CAR T-cell therapies and bispecific antibodies available for patients with multiple myeloma.

BCMA-directed therapies represent the next wave of therapeutic innovation for patients with multiple myeloma, Berdeja says. The treatment backbone for patients in this population is comprised of immunomodulatory agents (IMiDs), proteasome inhibitors (PIs,) and anti-CD38 monoclonal antibodies, Berdeja notes. However, once patients have exhausted all 3 of these drug classes, BCMA-directed products may be an effective next line of therapy, according to Berdeja. Four BCMA-directed products are currently approved by the FDA for patients with relapsed/refractory multiple myeloma who have received 4 or more prior lines of therapy, including an IMiD, a PI, and an anti-CD38 monoclonal antibody.

Teclistamab-cqyv (Tecvayli) was the first bispecific antibody to be approved by the FDA for this population in 2022. Its approval was supported by findings from the phase 1/2 MajesTEC-1 trial (NCT04557098), in which the agent elicited an overall response rate (ORR) of 61.8% (95% CI, 52.1%-70.9%). The second bispecific antibody, elranatamab-bcmm (Elrexfio), was approved in August, 2023, supported by findings from the phase 2 MagnetisMM-3 trial (NCT04649359), in which the agent elicited an ORR of 58%.

The first BCMA-directed CAR T-cell therapy to gain approval for patients in this population was idecabtagene vicleucel (Abecma), which was approved in 2021 based on findings from the phase 2 KarMMa trial, in which the agent elicited an ORR of 72% (95% CI, 62%-81%). Subsequently, ciltacabtagene autoleucel (Carvykti) was approved in 2022. The regulatory decision was supported by findings from the phase 1b/2 CARTITUDE-1 trial (NCT03361748), in which the agent elicited an ORR of 98% (95% CI, 92.7%-99.7%). Additional research is needed to determine how to best use each of the 4 products, as well as how they may be sequenced going forward, Berdeja concludes.