Impact of body mass index on anti-BCMA chimeric antigen receptor T-cell therapy outcomes in multiple myeloma

Overweight patients with relapsed/refractory myeloma have worse outcomes with anti-BCMA CAR-T than normal weight or overweight patients. Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T cell therapy (CAR-T) has transformed the treatment of relapsed/refractory multiple myeloma (MM), yet host determinants of efficacy remain poorly defined. While obesity influences immunotherapy outcomes in numerous cancers, the relationship between body mass index (BMI) and CAR-T outcomes in MM is unclear. We retrospectively evaluated MM patients treated with anti-BCMA CAR-T at Massachusetts General Hospital from 2016-2023. Cubic spline modeling revealed a nonlinear U-shaped association between BMI and progression free survival (PFS). Overweight patients (BMI 25-29.9 kg/m 2 ) displayed worse outcomes than normal weight (BMI <25 kg/m 2 ) or obese (BMI ≥30.0 kg/m 2 ) patients: 12-month PFS was 28.8% vs. 51.9% and 62.6% (P<0.001); 12-month overall survival (OS) was 61.4% vs. 82.9% and 84.2% (P=0.006); complete response rate was 36.4% vs. 42.9% and 56.1% (P=0.185) in the overweight, normal weight, and obese groups, respectively. Overweight patients also had inferior PFS and OS in multivariable models. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) incidence and severity did not significantly differ by BMI. These data support the presence of a U-shaped relationship between BMI and CAR-T outcomes in MM, which should motivate mechanistic studies to identify modifiable biologic factors mediating this observation.