sTable 1 shows radiation characteristics of Group A, B, and C. sTable 2 shows characteristics of CART-BCMA cells during manufacturing and at peak expansion in vivo in Group A, B, and C. sTable 3 shows details of radiation received after CART-BCMA therapy. sFigure 1 shows soluble BCMA serum levels before cyclophosphamide lymphodepletion on Day -3. sFigure 2 shows that prior radiation exposure is not associated with the level of CART-BCMA cells in vivo at peak expansion. sFigure 3 shows radiation was not associated with the level of persistent CART-BCMA cells in peripheral blood at Day 28. sFigure 4 shows level of CART-BCMA cells at peak expansion and Day 28 correlated with clinical response, and within responders, receipt of prior radiation was not associated with differences in CART=BCMA levels.
ARTICLE ABSTRACTB-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.
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.
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 (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.
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.