Dr. Atrash on the Evolution of BCMA-Directed Therapies in Multiple Myeloma

Shebli Atrash, MD, member, Plasma Cell Disorders Program, Levine Cancer Institute, Atrium Health, discusses the development and current use of BCMA-targeted antibody-drug conjugates (ADCs) and CAR T-cell therapies for the treatment of patients with multiple myeloma.

BCMA is a relatively new actionable target for multiple myeloma, Atrash states. Belantamab mafodotin-blmf (Blenrep) was the first BCMA-directed therapy to be approved by the FDA in 2020 based on data from the phase 2 DREAMM-2 study (NCT03525678), which showed a promising overall response rate (ORR) in a relapsed/refractory population.

The emergence of BCMA-directed CAR T-cell therapy has also had a profound effect on the multiple myeloma treatment landscape, Atrash continues. In 2021, idecabtagene vicleucel (Abecma) became the first cell-based gene therapy to gain FDA approval for multiple myeloma based on a high ORR. A second CAR T-cell therapy, ciltacabtagene autoleucel (Carvykti) also displayed a high ORR in the phase 1b/2 CARTITUDE-1 trial (NCT03548207), cementing it as a highly effective treatment option in the relapsed/refractory setting.

Despite these clinical advances, it is important to evaluate the different safety and toxicity profiles of each drug class, Atrash cautions. The main limitation of belantamab mafodotin is its high rate of corneal toxicity, whereas both CAR T products have a greater incidence of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome. Evaluation and management of these adverse effects are integral to mitigating risk, Atrash concludes.