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

Relapsed or refractory multiple myeloma (RRMM) patients with extraosseous extramedullary disease (EMD) have inferior outcomes and lack effective therapies. We developed anti-BCMA/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 RRMM patients with extraosseous EMD, and anti-BCMA/GPRC5D bispecific CAR T cells were administered at 2·0×10⁶ CAR T cells per kilogram. At a median follow-up of 10·1 months (IQR 6·4-19·1), 36 (97%) of 37 patients obtained an overall response and measurable residual disease (MRD) negativity, including 16 (43%) with stringent complete response (sCR). The median progression-free survival (PFS) was 5·8 months (95% confidence interval [CI]: 2·2-9·4), and the median overall survival (OS) was not reached. The most common grade 3 or worse adverse events were hematologic toxicities (except lymphopenia) (37/37). 27 (73%) patients experienced cytokine release syndrome (CRS), of which all cases were grade 1 or 2. Two (5%) patients had grade 1 or 3 immune effector cell-associated neurotoxicity syndrome (ICANS). These findings support that anti-BCMA/GPRC5D bispecific CAR T cells induced a high response rate in RRMM patients with extraosseous EMD, and the safety profile was manageable. This trial was registered with ClinicalTrials.gov (NCT05509530) and is ongoing.