BCMAtargeting

BCMA targeting refers to therapeutic approaches directed at the B-cell maturation antigen (BCMA, TNFRSF17), a cell-surface receptor strongly expressed on malignant plasma cells in multiple myeloma and to a lesser extent on normal plasma cells. BCMA is a member of the TNF receptor superfamily and supports plasma cell survival through ligands such as BAFF and APRIL. Its restricted normal tissue distribution and high expression on myeloma cells have made BCMA a focal point for immune-based therapies.

BCMA serves as the target for several therapeutic modalities. Chimeric antigen receptor (CAR) T cell therapies engineer a patient’s T cells to recognize BCMA and attack BCMA-positive cells; two examples are idecabtagene vicleucel (ide-cel, Abecma) and ciltacabtagene autoleucel (cilta-cel, Carvykti). Antibody-drug conjugates link a cytotoxic payload to an anti-BCMA antibody, such as belantamab mafodotin (belantamab). Bispecific antibodies recruit T cells to BCMA-expressing cells by simultaneously binding BCMA and CD3, with teclistamab (Tecvayli) as a leading example.

Clinical status and approvals have evolved rapidly. BCMA-targeted CAR-T therapies are approved in many regions for relapsed or refractory multiple myeloma after preceding lines of therapy, with ide-cel and cilta-cel representing early milestone entrants. Belantamab mafodotin was approved as an anti-BCMA antibody-drug conjugate for RRMM, though ocular toxicity requires careful monitoring. Teclistamab, a BCMA×CD3 bispecific, has also gained regulatory traction. Ongoing trials explore combinations, sequencing with other therapies, and strategies to overcome resistance and improve safety.

Safety considerations include on-target toxicities such as hypogammaglobulinemia and increased infection risk, cytokine release syndrome and neurotoxicity with CAR-T and bispecifics, and ocular toxicity with belantamab. Antigen loss and disease progression due to BCMA downregulation remain challenges, along with manufacturing and access limitations.