biostudies-literatureManjunath SHNCI NIH HHSNIH6580-6590https://www.ebi.ac.uk/biostudies/studies/S-EPMC8639780biostudies-literatureUnknown27(23)<h4>Purpose</h4>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 I trial of CART-BCMA.<h4>Experimental design</h4>Twenty-five r/rMM subjects were treated in three cohorts with two doses of CART-BCMA cells ± cyclophosphamide. We retrospectively analyzed toxicity, response, and CART manufacturing data based on RT receipt.<h4>Results</h4>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 (range 18-35). Group C had qualitatively lower rates of grade 4 (G4) hematologic toxicities (25%) versus 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 cytokine release syndrome was observed in 38.5%, 25%, and 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 (<i>P</i> = 0.002) and <100 days (<i>P</i> = 0.069) before apheresis was associated with lower <i>in vitro</i> proliferation during manufacturing; however, <i>in vivo</i> CART-BCMA expansion appeared similar across groups.<h4>Conclusions</h4>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.Clinical cancer research : an official journal of the American Association for Cancer ResearchThe Safety of Bridging Radiation with Anti-BCMA CAR T-Cell Therapy for Multiple Myeloma.PMC8639780P01 CA2142781P01CA214278Maxwell RCohen ADManjunath SHJones JAStadtmauer EAMelenhorst JJGarfall ALJune CHPlastaras JPPaydar ILevine BLMilone MCDavis MMLacey SFArscott WTMaity AfalseThe Safety of Bridging Radiation with Anti-BCMA CAR T-Cell Therapy for Multiple Myeloma.<h4>Purpose</h4>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 I trial of CART-BCMA.<h4>Experimental design</h4>Twenty-five r/rMM subjects were treated in three cohorts with two doses of CART-BCMA cells ± cyclophosphamide. We retrospectively analyzed toxicity, response, and CART manufacturing data based on RT receipt.<h4>Results</h4>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 (range 18-35). Group C had qualitatively lower rates of grade 4 (G4) hematologic toxicities (25%) versus 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 cytokine release syndrome was observed in 38.5%, 25%, and 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 (<i>P</i> = 0.002) and <100 days (<i>P</i> = 0.069) before apheresis was associated with lower <i>in vitro</i> proliferation during manufacturing; however, <i>in vivo</i> CART-BCMA expansion appeared similar across groups.<h4>Conclusions</h4>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.2021-01-01T00:00:00Z2021 Dec2026-05-10T03:47:10.254Z2024-11-20T17:21:54.972ZS-EPMC86397803452636510.1158/1078-0432.ccr-21-030810.1158/1078-0432.CCR-21-0308