BCMAxCD3

BCMAxCD3 refers to a class of bispecific antibodies designed to treat multiple myeloma by simultaneously binding BCMA on malignant plasma cells and CD3 on T cells. By bringing T cells into close contact with BCMA-expressing cells, these agents redirect T-cell cytotoxicity toward the tumor, promoting tumor cell lysis and an anti-tumor immune response. Teclistamab, marketed as Tecvayli, is a leading example of a BCMAxCD3 bispecific antibody developed by Janssen Biotech and Genmab. It is designed as an IgG-based bispecific that engages BCMA on myeloma cells and CD3 on T cells, thereby activating T cells to kill BCMA-expressing cells. In phase 1/2 studies, teclistamab has demonstrated clinically meaningful activity in adults with relapsed or refractory multiple myeloma, including patients with prior therapies such as proteasome inhibitors, IMiDs, and anti-CD38 antibodies.

Administration and safety considerations for BCMAxCD3 antibodies typically involve subcutaneous dosing with a step-up ramp to mitigate cytokine release syndrome (CRS) and other toxicities. Common adverse events include CRS, infections, cytopenias, fatigue, and infusion-related reactions; some events may be severe and require appropriate clinical management. The BCMA target is expressed on a majority of malignant plasma cells in multiple myeloma and to a much lesser extent on normal tissues, which underpins the therapeutic rationale for BCMA-directed T-cell engagement. Nonetheless, challenges remain, including antigen downregulation or loss, CRS, infections, and other immune-related toxicities. Ongoing development of BCMAxCD3 agents focuses on optimizing efficacy, minimizing toxicity, and exploring combination strategies to broaden benefit across patient populations.