Phase 1 trial tests concurrent BCMA and GPRC5D CAR T cells in myeloma

This phase 1 dose-escalation trial evaluated MCARH125, a BCMA-directed CAR T-cell therapy, alone or infused concurrently with MCARH109, which targets GPRC5D. The 15 participants had relapsed or refractory multiple myeloma; six received MCARH125 alone and nine received both products. The primary objective was to establish the safety of concurrent infusion.

Among patients receiving both CAR T-cell products, the overall response rate was 78%, and median progression-free survival was 18.2 months. One patient in each treatment group developed immune effector cell–associated hemophagocytic syndrome. No grade 3 or higher cytokine release syndrome or immune effector cell–associated neurologic syndrome was reported.

Correlative analyses suggested that antigen loss may contribute to resistance despite dual-targeting. Patients receiving both products also had significantly less BCMA CAR T-cell expansion than those receiving BCMA CAR T cells alone, despite equivalent BCMA CAR T-cell doses at infusion. These findings come from a small phase 1 study and do not establish comparative efficacy; the results support further evaluation of concurrent dual-target CAR T-cell therapy. The trial was registered as NCT05431608.