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

ABSTRACT: 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.