Trending topics and news in HCT and Cellular Therapy

Concurrent Administration of BCMA and GPRC5D Chimeric Antigen Receptor (CAR) T Cells in Advanced Multiple Myeloma

A recent phase I study (NCT05431608), from Memorial Sloan Kettering Cancer Center, has concluded that concurrent infusion of BCMA- and GPRC5D-targeted CAR T cells is a feasible and promising treatment for pretreated relapsed or refractory multiple myeloma. Published in Blood, the findings suggests that simultaneously targeting two heterogeneously expressed myeloma antigens could broaden tumour coverage, although interactions between the two CAR T-cell populations may influence their expansion and effectiveness.

BCMA- and GPRC5D-directed therapies are individually active in advanced myeloma, but malignant plasma cells can vary in their expression of these antigens, allowing antigen-negative cells to escape treatment. The investigators therefore conducted a dose-escalation trial of the BCMA-directed product (MCARH125), administered either alone or concurrently with the GPRC5D-directed product (MCARH109). Overall, the primary objective was to establish the safety of concurrent infusion. Fifteen patients were treated across three dose levels: six received MCARH125 alone and nine received both CAR T-cell products.

Concurrent treatment produced an overall response rate of 78%, with a median progression-free survival of 18.2 months. Toxicities were generally manageable, with one patient in the MCARH125-only group and one in the dual-infusion group developping immune effector cell-associated haemophagocytic syndrome. No patients experienced grade 3 or higher cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). Correlative analyses indicated that antigen loss remained a potential resistance mechanism despite dual targeting. Despite receiving equivalent BCMA CAR T-cell doses, patients receiving both products had significantly less BCMA CAR T-cell expansion than those receiving MCARH125 alone. This suggests that expansion of one CAR population may restrict the other. The authors conclude that dual BCMA/GPRC5D CAR T-cell infusion is safe and potentially effective, but future strategies may need to optimise the balance, timing, and expansion of each CAR population.

Reference:

Mailankody S, Mitra S, Herrera K, et al. Concurrent administration of BCMA and GPRC5D chimeric antigen receptor (CAR) T cells in advanced multiple myeloma. Blood. Published online July 7, 2026. https:/doi.org/10.1182/blood.2025032122