Anti-BCMA/GPRC5D CAR T cells in patients with relapsed or refractory multiple myeloma who have extraosseous...

Patients with relapsed or refractory multiple myeloma (RRMM) with extraosseous extramedullary disease (EMD) have inferior outcomes and lack effective therapies. We developed anti-B-cell maturation antigen (anti-BCMA)/G protein-coupled receptor, class C group 5 member D (GPRC5D) bispecific chimeric antigen receptors (CARs) to investigate the activity and safety of the CAR T cells in patients with extraosseous EMD. In this single-arm, open-label, phase 2 trial, we enrolled 37 patients with RRMM with extraosseous EMD, and anti-BCMA/GPRC5D bispecific CAR T cells were administered at 2.0 × 106 CAR T cells per kg. At a median follow-up of 10.1 months (interquartile range, 6.4-19.1), 36 of 37 patients (97%) obtained an overall response and measurable residual disease negativity, including 16 (43%) with stringent complete response. The median progression-free survival was 5.8 months (95% confidence interval, 2.2-9.4), and the median overall survival was not reached. The most common grade 3 or worse adverse events were hematologic toxicities (except lymphopenia; 37/37). Twenty-seven patients (73%) experienced cytokine release syndrome, all cases of which were grade 1 or 2. Two patients (5%) had grade 1 or 3 immune effector cell-associated neurotoxicity syndrome. These findings support that anti-BCMA/GPRC5D bispecific CAR T cells induced a high response rate in patients with RRMM with extraosseous EMD, and the safety profile was manageable. This ongoing trial is registered at www.clinicaltrials.gov as NCT05509530.