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 I trial of CART-BCMA. Experimental Design: 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. 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 (range [18–35][1]). 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. 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. [1]: #ref-18

中文翻译：

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抗 BCMA CAR T 细胞治疗多发性骨髓瘤的桥接放射治疗的安全性

目的：B 细胞成熟抗原 (BCMA) 靶向嵌合抗原受体 (CAR) T 细胞 (CART-BCMA) 是治疗复发/难治性多发性骨髓瘤 (r/rMM) 的一种有前途的治疗方法。我们评估了接受 CART-BCMA I 期试验的受试者接受桥接放射 (RT) 的安全性和可行性。实验设计：25 名 r/rMM 受试者分为三个队列，接受两剂 CART-BCMA 细胞±环磷酰胺治疗。我们根据 RT 收据回顾性分析了毒性、反应和 CART 生产数据。结果：13 名受试者在 CART 输注前 1 年内未接受 RT（A 组）。八名受试者在 CART 输注前不到 1 年接受 RT（B 组），从 RT 到血浆分离术的中位时间为 114 天（范围 40-301）。四名受试者接受桥接放疗（C 组），中位剂量为 22 Gy，从放疗到输注的时间为 25 天（范围 [18-35][1]）。C 组的 4 级 (G4) 血液学毒性发生率 (25%) 明显低于 A 组 (61.5%) 和 B 组 (62.5%)。A、B 和 C 组中 G3-4 神经毒性的发生率分别为 7.7%、25% 和 25%。A、B 和 C 组中观察到 G3-4 细胞因子释放综合征的比例分别为 38.5%、25% 和 25%。A、B 和 C 组中分别有 54%、38% 和 50% 的人出现部分缓解或更好。在血浆分离术前进行 RT <1 年 (P = 0.002) 和 <100 天 (P = 0.069) 与生产过程中较低的体外增殖相关；然而，体内 CART-BCMA 扩增在各组之间似乎相似。结论：在我们的 r/rMM 患者中，CART-BCMA 治疗的桥接 RT 似乎是安全可行的，尽管未来需要更大规模的研究来得出明确的结论。[1]：#ref-18