BCMA/GPRC5D bispecific CAR T-cell therapy for relapsed/refractory multiple myeloma with extramedullary disease: a single-center, single-arm, phase 1 trial

Publication Brief

BCMA/GPRC5D bispecific CAR T-cell therapy for relapsed/refractory multiple myeloma with extramedullary disease: a single-center, single-arm, phase 1 trial

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.  

Journal: Lancet Haematol. 2024 Oct.

Volume / Pages: 11(10):e751-e760

DOI:10.1186/s13045-025-01713-2

PubMed: PubMed: 42166352