American Association for Cancer Research
10780432ccr210308-sup-259606_3_supp_7344293_qy9km5.pdf (747.34 kB)

sTable 1, sTable 2, sTable 3, sFigure 1, sFigure 2, sFigure 3, sFigure 4 from The Safety of Bridging Radiation with Anti-BCMA CAR T-Cell Therapy for Multiple Myeloma

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journal contribution
posted on 2023-03-31, 23:11 authored by Shwetha H. Manjunath, Adam D. Cohen, Simon F. Lacey, Megan M. Davis, Alfred L. Garfall, J. Joseph Melenhorst, Russell Maxwell, W. Tristram Arscott, Amit Maity, Joshua A. Jones, John P. Plastaras, Edward A. Stadtmauer, Bruce L. Levine, Carl H. June, Michael C. Milone, Ima Paydar

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.





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. 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.