Anito-cel（d结构域BCMA CAR-T）治疗复发难治多发性骨髓瘤的1期研究
Phase 1 Study of Anito-cel, a d-Domain BCMA CAR T Cell for Refractory or Recurrent Myeloma
多发性骨髓瘤经过多线治疗后常复发，需要新疗法。Anito-cel是一种靶向BCMA（B细胞成熟抗原）的自体CAR-T（改造患者自身T细胞来攻击肿瘤），采用新型合成d结构域结合臂。1期试验纳入40人、38人接受治疗，推荐剂量下94%出现1–2级细胞因子释放综合征、无3级以上；仅16%有1–2级神经毒性。中位随访38.1个月，全部38人（100%）有效，79%完全缓解，24个月无进展生存率57%，36个月总生存率65%。体外比较提示该结合臂细胞因子释放更少。
为什么推荐给您：全新BCMA结合结构域CAR-T首次人体结果，疗效高且毒性低，属重要新模态。
不需要生物学背景，多打比方
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摘要Abstract
BACKGROUND: Anitocabtagene autoleucel (anito-cel), a B-cell maturation antigen (BCMA)-directed autologous chimeric antigen receptor (CAR) T-cell therapy with a synthetic d-domain binder (ddBCMA), may have efficacy in patients with relapsed or refractory multiple myeloma.
METHODS: In a phase 1 study, we evaluated the safety and efficacy of anito-cel (dose level 1, 100×10^6 CAR+ T cells; dose level 2, 300×10^6 CAR+ T cells) in patients with relapsed or refractory multiple myeloma who had received three or more lines of therapy previously or had triple-class refractory disease. Primary end points were adverse events during the treatment period and establishment of the recommended phase 2 dose. In complementary in vitro studies, we compared the anito-cel ddBCMA binder with a dual variable heavy-chain domain of a heavy chain-only antibody (dual-VHH) binder corresponding to the published sequence for ciltacabtagene autoleucel.
RESULTS: Of 40 patients enrolled, 38 received anito-cel. All 38 patients had an adverse event during the treatment period, and 37 patients (97%) had an adverse event of grade 3 or higher. Among patients who received the recommended phase 2 dose (100×10^6 CAR+ T cells), 94% had cytokine release syndrome of grade 1 or 2, with no events of grade 3 or higher. A total of 16% of the patients had immune effector cell-associated neurotoxicity syndrome (ICANS) of grade 1 or 2, and 1 patient (3%) had a grade 3 event. No non-ICANS or delayed neurotoxic effects occurred. At a median follow-up of 38.1 months, all 38 patients (100%) had had a response, with 79% having a complete response. The 24-month progression-free survival was 57%; the median progression-free survival was 30.2 months. The 36-month overall survival was 65%. The ddBCMA binder had a faster off-rate than the dual-VHH binder; although cytotoxicity was similar with the two therapies, ddBCMA CAR T cells led to less cytokine release and did not result in activation without antigen or in off-target cytotoxic effects.
CONCLUSIONS: Anito-cel therapy led to a high incidence of response among patients with heavily pretreated relapsed or refractory multiple myeloma. Cytokine release syndrome and ICANS of grade 3 or higher were rare. (Funded by Arcellx and Kite, a Gilead company; ClinicalTrials.gov number, NCT04155749.).