Beyond the Plasma Cell: Why Anti-BCMA Bispecifics Increase Infection Risk via Early B-Cell Depletion

Highlights

• Anti-BCMA bispecific antibodies (bsAbs) cause more severe and frequent infections in multiple myeloma (MM) patients compared to anti-GPRC5D bsAbs.
• The mechanism involves the unexpected expression of BCMA on early B-cell precursors, specifically small pre-B cells, leading to their depletion.
• In contrast, GPRC5D expression is highly restricted to malignant and normal plasma cells, sparing the earlier B-cell lineage.
• This study provides a biological rationale for individualized therapy selection based on a patient’s baseline infection risk and immune status.

Background: The Challenge of Infections in Modern Myeloma Therapy