The Safety of Bridging Radiation with Anti-BCMA CAR T-Cell Therapy for Multiple Myeloma

PURPOSE B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T-cells (CART-BCMA) are a promising treatment for relapsed/refractory multiple myeloma (r/rMM). We evaluated the safety and feasibility of bridging radiation (RT) in subjects treated on a phase 1 trial of CART-BCMA. EXPERIMENTAL DESIGN Twenty-five r/rMM subjects were treated in 3 cohorts with two doses of CART-BCMA cells +/- cyclophosphamide. We retrospectively analyzed toxicity, response, and CART manufacturing data based on RT receipt. RESULTS Thirteen subjects received no RT <1 year before CART infusion (Group A). Eight subjects received RT <1 year before CART infusion (Group B) with median time from RT to apheresis of 114 days (range 40-301). Four subjects received bridging-RT (Group C) with a median dose of 22 Gy and time from RT to infusion of 25 days (18-35). Group C had qualitatively lower rates of grade 4 (G4) hematologic toxicities (25%) vs. A (61.5%) and B (62.5%). G3-4 neurotoxicity occurred in 7.7%, 25%, and 25% in Group A, B, and C, respectively. G3-4 CRS was observed in 38.5%, 25%, 25% in Group A, B, and C, respectively. Partial response or better was observed in 54%, 38%, and 50% of Group A, B, and C, respectively. RT administered <1 year (p=0.002) and <100 days (p=0.069) before apheresis was associated with lower in vitro proliferation during manufacturing; however, in vivo CART-BCMA expansion appeared similar across groups. CONCLUSIONS Bridging-RT appeared safe and feasible with CART-BCMA therapy in our r/rMM patients, though larger future studies are needed to draw definitive conclusions.