Concurrent administration of BCMA and GPRC5D CAR T cells for advanced multiple myeloma.

Concurrent BCMA and GPRC5D CAR T cell therapy in heavily pre-treated multiple myeloma shows an 78% overall response rate with a median PFS of 18.2 months in a phase I trial.

• Why it matters: High heterogeneity in antigen expression in malignant plasma cells may limit the effectiveness of single-antigen therapies, highlighting the need for dual-targeting approaches to improve outcomes in relapsed or refractory myeloma.
• What they did: A phase I dose escalation trial treated 15 patients with either BCMA CAR T cells alone or in combination with GPRC5D CAR T cells, assessing safety and immune responses across three dose levels, with correlative analyses on CAR T cell expansion and resistance mechanisms.
• The result: The co-infusion was well tolerated with no grade 3 or higher CRS or ICANS, and showed promising efficacy; however, dual CAR therapy was associated with reduced BCMA CAR T cell expansion, suggesting antigen loss and limited CAR T cell proliferation may contribute to resistance.