Chimeric antigen receptor (CAR)-T cell therapy showed preliminary activity in patients with refractory or relapsed T cell acute lymphoblastic leukemia (r/r T-ALL). However, many obstacles remain, including manufacturing difficulties and risk of infections. This phase I study (NCT04840875) evaluated autologous CD7 CAR-T cells manufactured without pre-selection of healthy T cells in r/r T-ALL. Thirty patients (29 children and one adult) with a median of two lines of prior therapy but without detectable peripheral leukemia were enrolled. Excluding three cases of manufacturing failures, a total of 27 (90%) patients received infusions after products were confirmed free of leukemia contamination, including 16 (59%) meeting planned target doses. Common adverse events within 30 days included grade 3–4 cytopenias (100%), grade 1–2 (70%) and 3–4 (7%, including one dose-limiting toxicity) cytokine release syndrome, grade 1 neurotoxicity (7%), grade 2 infection (4%), and grade 2 graft-versus-host disease (4%). Two patients developed grade 2 infections after day 30. At day 30, 96% responded and 85% achieved complete remission (CR) or CR with incomplete hematologic recovery (CRi). Seventy-four percent underwent transplantation. Twelve-month progression-free survival with and without censoring transplantation was 22% (95% confidence interval 4%–100%) and 57% (41%–81%), respectively. These results support that autologous CD7 CAR-T therapy without T cell pre-selection is feasible in patients with r/r T-ALL.

中文翻译：

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在患有复发/难治性 T-ALL 的儿科患者中无需 T 细胞预选即可生成自体 CD7 CAR-T 细胞：一项 I 期试验


嵌合抗原受体 (CAR)-T 细胞疗法在难治性或复发性 T 细胞急性淋巴细胞白血病 (r/r T-ALL) 患者中显示出初步活性。然而，仍然存在许多障碍，包括制造困难和感染风险。这项 I 期研究 (NCT04840875) 评估了在 r/r T-ALL 中未预先选择健康 T 细胞而制造的自体 CD7 CAR-T 细胞。纳入了 30 名患者（29 名儿童和 1 名成人），之前平均接受过两线治疗，但没有检测到外周白血病。排除三起生产失败案例，在产品被确认无白血病污染后，共有 27 名患者（90%）接受了输液，其中 16 名患者（59%）达到了计划的目标剂量。 30天内常见的不良事件包括3-4级血细胞减少（100%）、1-2级（70%）和3-4级（7%，包括一种剂量限制性毒性）细胞因子释放综合征、1级神经毒性（7%） ）、2 级感染（4%）和 2 级移植物抗宿主病（4%）。两名患者在第 30 天后出现 2 级感染。第 30 天时，96% 的患者有反应，85% 的患者达到完全缓解 (CR) 或血液学不完全恢复的 CR (CRi)。百分之七十四接受了移植。有和没有审查移植的 12 个月无进展生存率分别为 22%（95% 置信区间 4%–100%）和 57%（41%–81%）。这些结果表明，无需 T 细胞预选的自体 CD7 CAR-T 疗法对于 r/r T-ALL 患者是可行的。