肿瘤细胞治疗研究
英文原题：Long-term follow-up of donor-derived CD7 CAR T-cell therapy in patients with T-cell acute lymphoblastic leukemia.
在这项 2 年随访分析中，供者来源的 CD7 CAR T 细胞治疗在部分 r/r T-ALL 患者中显示出持久的疗效。
背景：此前一项 I 期试验报告显示，供者来源的 CD7 靶向嵌合抗原受体（CAR）T 细胞可用于难治或复发 T 细胞急性淋巴细胞白血病（r/r T-ALL），并显示早期疗效；中位随访时间为 6.3 个月。本文报告 2 年随访后的长期安全性和活性。 方法：参与者接受来自既往干细胞移植（SCT）供者或 HLA 匹配新供者的 CD7 靶向 CAR T 细胞，输注前进行淋巴细胞清除。目标剂量为每千克患者体重 1×10⁶（±30%）个 CAR T 细胞。主要终点为安全性，疗效为次要终点。本报告聚焦长期随访，并结合既往报告的早期结局进行讨论。 结果：20 名参与者入组并接受 CD7 CAR T 细胞输注。中位随访 27.0 个月（范围 24.0–29.3）后，总缓解率和完全缓解率分别为 95%（19/20）和 85%（17/20），35%（7/20）患者随后接受 SCT。6 例患者复发，中位复发时间为 6 个月（范围 4.0–10.9）；其中 4 例肿瘤细胞丢失 CD7 表达。治疗后 24 个月无进展生存率（PFS）和总生存率（OS）分别为 36.8%（95% CI：13.8%–59.8%）和 42.3%（95% CI：18.8%–65.8%）；PFS 和 OS 中位数分别为 11.0 个月（95% CI：6.7–12.5）和 18.3 个月（95% CI：12.5–20.8）。既往报告的短期不良事件（治疗后<30 天）包括 3–4 级细胞因子释放综合征（CRS；10%）和 1–2 级移植物抗宿主病（GVHD；60%）。治疗后>30 天报告的严重不良事件包括 5 例感染和 1 例 4 级肠道 GVHD。尽管 CD7 CAR T 细胞持续存在良好，非 CAR T 细胞和 NK 细胞主要为 CD7 阴性；约半数参与者的这些细胞最终恢复至正常水平。 结论：这项 2 年随访分析显示，供者来源 CD7 CAR T 细胞治疗可使部分 r/r T-ALL 患者获得持久疗效。疾病复发是治疗失败的主要原因，重度感染是值得关注的迟发不良事件。 试验注册：ChiCTR2000034762。
BACKGROUND: Donor-derived CD7-directed chimeric antigen receptor (CAR) T cells showed feasibility and early efficacy in patients with refractory or relapsed T-cell acute lymphoblastic leukemia (r/r T-ALL), in a previous phase I trial report, at a median follow-up of 6.3 months. Here we report long-term safety and activity of the therapy after a 2-year follow-up. METHODS: Participants received CD7-directed CAR T cells derived from prior stem cell transplantation (SCT) donors or from HLA-matched new donors after lymphodepletion. The target dose was 1 10 6 ( 30%) CAR T cells per kg of patient weight. The primary endpoint was safety with efficacy secondary. This report focuses on the long-term follow-up and discusses them in the context of previously reported early outcomes. RESULTS: Twenty participants were enrolled and received infusion with CD7 CAR T cells. After a median follow-up time of 27.0 (range, 24.0-29.3) months, the overall response rate and complete response rate were 95% (19/20 patients) and 85% (17/20 patients), respectively, and 35% (7/20) of patients proceeded to SCT. Six patients experienced disease relapse with a median time-to-relapse of 6 (range, 4.0-10.9) months, and 4 of these 6 patients were found to have lost CD7 expression on tumor cells. Progression-free survival (PFS) and overall survival (OS) rates 24 months after treatment were respectively 36.8% (95% CI, 13.8-59.8%) and 42.3% (95% CI, 18.8-65.8%), with median PFS and OS of respectively 11.0 (95% CI, 6.7-12.5) months and 18.3 (95% CI, 12.5-20.8) months. Previously reported short-term adverse events (< 30 days after treatment) included grade 3-4 cytokine release syndrome (CRS; 10%) and grade 1-2 graft-versus-host disease (GVHD; 60%). Serious adverse events reported > 30 days after treatment included five infections and one grade 4 intestinal GVHD. Despite good CD7 CAR T-cell persistence, non-CAR T and natural killer cells were predominantly CD7-negative and eventually returned to normal levels in about half of the participants. CONCLUSIONS: In this 2-year follow-up analysis, donor-derived CD7 CAR T-cell treatment demonstrated durable efficacy in a subset of patients with r/r T-ALL. Disease relapse was the main cause of treatment failure, and severe infection was a noteworthy late-onset adverse event. TRIAL REGISTRATION: ChiCTR2000034762.
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