CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
ZUMA-4 I 期三年结果：KTE-X19 治疗儿童复发/难治性急性淋巴细胞白血病
英文原题：Three-year results from phase I of ZUMA-4: KTE-X19 in pediatric relapsed/refractory acute lymphoblastic leukemia.
查看英文原题
Three-year results from phase I of ZUMA-4: KTE-X19 in pediatric relapsed/refractory acute lymphoblastic leukemia.
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中文摘要
本文报告ZUMA-4的3年结果。这是一项Ⅰ/Ⅱ期多中心研究，评估自体抗CD19嵌合抗原受体（CAR）T细胞疗法KTE-X19治疗复发/难治性B细胞急性淋巴细胞白血病儿童及青少年患者的安全性和疗效。Ⅰ期研究评估了两个剂量水平和制剂，主要终点为剂量限制性毒性的发生率。研究共纳入31例患者，其中24例接受KTE-X19治疗；中位年龄13.5岁（范围3–20岁），中位随访36.1个月。未观察到剂量限制性毒性。所有接受治疗的患者均发生3级不良事件，常见事件包括低血压（50%）和贫血（42%）。所有治疗患者中，3级细胞因子释放综合征发生率为33%；接受2×10⁶个CAR-T 细胞/kg剂量者为75%，接受1×10⁶个/kg、68 mL制剂者为27%，接受1×10⁶个/kg、40 mL制剂者为22%。
相应剂量组3级神经系统事件发生率分别为21%、25%、27%和11%。所有接受治疗患者的完全缓解率（包括血液学恢复不完全的完全缓解）为67%；按剂量组依次为75%、64%和67%。应答者的总体微小残留病灶阴性率为100%，其中88%随后接受异基因干细胞移植。在1×10⁶个/kg、40 mL制剂组（推荐Ⅱ期剂量）中，经异基因移植删失的中位缓解持续时间及中位总生存期均未达到。单次KTE-X19治疗使复发/难治性B细胞急性淋巴细胞白血病儿童和青少年患者获得较高的微小残留病灶阴性缓解率，且安全性可控。研究Ⅱ期正在以1×10⁶个CAR-T 细胞/kg、40 mL制剂继续开展。ClinicalTrials.gov：NCT02625480。
展开英文摘要原文
Here we present the 3-year results of ZUMA-4, a phase I/II multicenter study evaluating the safety and efficacy of KTEX19, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in pediatric/adolescent patients with relapsed/refractory B-cell acute lymphoblastic leukemia. Phase I explored two dose levels and formulations. The primary endpoint was the incidence of dose-limiting toxicities. Thirty-one patients were enrolled; KTE-X19 was administered to 24 patients (median age 13. 5 years, range 3-20; median follow-up 36.
1 months). No dose-limiting toxicities were observed. All treated patients had grade 3 adverse events, commonly hypotension (50%) and anemia (42%). Grade 3 cytokine release syndrome rates were 33% in all treated patients, 75% in patients given the dose of 2 106 CAR T cells/kg, 27% in patients given the dose of 1 106 cells/kg in the 68 mL formulation, and 22% in patients given the dose of 1 106 cells/kg in the 40 mL formulation; the percentages of patients experiencing grade 3 neurologic events were 21%, 25%, 27%, and 11% respectively.
Overall complete remission rates (including complete remission with incomplete hematologic recovery) were 67% in all treated patients, 75% in patients given 2 106 CAR T cells/kg, 64% in patients given 1 106 cells/kg in the 68 mL formulation, and 67% in patients given 1 106 cells/kg in the 40 mL formulation.
Overall minimal residual diseasenegativity rates were 100% among responders; 88% of responders underwent subsequent allogeneic stem-cell transplantation. In the 1 106 (40 mL) group (recommended phase II dose), the median duration of remission censored at allogeneic stem-cell transplantation and median overall survival were not reached.
Pediatric/adolescent patients with relapsed/refractory B-cell acute lymphoblastic leukemia achieved high minimal residual disease-negative remission rates with a manageable safety profile after a single dose of KTE-X19. Phase II of the study is ongoing at the dose of 1 106 CAR T cells/kg in the 40 mL formulation. ClinicalTrials. gov: NCT02625480.
论文信息
- 作者
- Wayne AS、Huynh V、Hijiya N、Rouce RH、Brown PA、Krueger J、Kitko CL、Ziga ED
- 单位
- Children's Hospital Los Angeles, USC Norris Comprehensive Cancer Center and Keck School of Medicine, University of Southern California, Los Angeles, CA. awayne@chla.usc.edu.United States
- 文献类型
- 多中心研究 · 非美国政府资助研究
- 期刊
- Haematologica2023 Mar 1
- 原文标识
- PubMed 36263840 · DOI 10.3324/haematol.2022.280678
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