肿瘤细胞治疗研究
英文原题：Ten-Year Outcomes after CAR T-Cell Therapy for B-Cell Lymphomas.
在接受过重度预治疗的B细胞非霍奇金淋巴瘤患者中，单次输注tisagenlecleucel使约三分之一的大B细胞淋巴瘤患者和近半数的滤泡性淋巴瘤患者获得了长达十年的缓解（无淋巴瘤生存）。
**背景：**抗 CD19 嵌合抗原受体（CAR）T 细胞疗法是复发或难治性 B 细胞非霍奇金淋巴瘤的标准治疗。其长期疗效和治愈潜力仍不确定。**方法：**我们评估了 38 例复发/难治性 B 细胞非霍奇金淋巴瘤患者的长期结局，其中大 B 细胞淋巴瘤 24 例、滤泡性淋巴瘤 14 例。患者接受 CTL019（现称 tisagenlecleucel）治疗，该产品为自体 T 细胞，表达 CD19 靶向且由 4-1BB 共刺激的嵌合受体。淋巴瘤无生存期定义为 tisagenlecleucel 输注至复发或淋巴瘤相关死亡的时间。采用 Aalen-Johansen 方法估算非复发相关死亡及第二原发癌发生率。数据截点为 2025 年 10 月 1 日。**结果：**中位随访 10.1 年（范围 7.9–11.5）时，超过 5.4 年未发生复发。大 B 细胞淋巴瘤患者的 10 年淋巴瘤无生存率为 32%（95% 置信区间 [CI] 14–51），滤泡性淋巴瘤患者为 47%（95% CI 20–71）。将任何原因死亡纳入分析后，大 B 细胞淋巴瘤患者的 10 年无进展生存率为 17%（95% CI 5–34），滤泡性淋巴瘤患者为 29%（95% CI 9–52）；相应的 10 年总生存率分别为 17%（95% CI 5–34）和 50%（95% CI 23–72）。2 例患者（5%）出现持续性 2 或 3 级中性粒细胞减少；未观察到迟发性贫血或血小板减少。9 例患者发生第二原发癌（10 年累积发生率 21%）。10 年非复发相关死亡率为 18%（排除 COVID-19 相关死亡后为 14%）。CAR 转基因持续性较高似乎与长期应答相关。长期应答患者中有 44% 持续存在 B 细胞缺失。**结论：**在既往接受多线治疗的 B 细胞非霍奇金淋巴瘤患者中，单次 tisagenlecleucel 输注可使约三分之一大 B 细胞淋巴瘤患者和近半数滤泡性淋巴瘤患者获得长达十年的缓解（淋巴瘤无生存）。
BACKGROUND: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a standard treatment for relapsed or refractory B-cell non-Hodgkin lymphomas. Long-term results and curative potential remain uncertain. METHODS: We evaluated long-term outcomes in 38 patients with relapsed or refractory B-cell non-Hodgkin lymphomas (24 patients with large B-cell lymphoma and 14 with follicular lymphoma) who had been treated with CTL019 (now called tisagenlecleucel) - autologous T cells expressing CD19-directed, 4-1BB-costimulated chimeric receptors. Lymphoma-free survival was defined as the time from the tisagenlecleucel infusion to relapse or lymphoma-related death. The incidence of non-relapse-related death and second primary cancer was estimated with the Aalen-Johansen method. The data-cutoff date was October 1, 2025. RESULTS: At a median follow-up of 10.1 years (range, 7.9 to 11.5), no relapses had occurred beyond 5.4 years. The 10-year lymphoma-free survival was 32% (95% confidence interval [CI], 14 to 51) among patients with large B-cell lymphoma and 47% (95% CI, 20 to 71) among those with follicular lymphoma. In an analysis that included deaths from any cause, the 10-year progression-free survival was 17% (95% CI, 5 to 34) among patients with large B-cell lymphoma and 29% (95% CI, 9 to 52) among those with follicular lymphoma; the 10-year overall survival was 17% (95% CI, 5 to 34) and 50% (95% CI, 23 to 72), respectively. Persistent grade 2 or 3 neutropenia occurred in 2 patients (5%); no late anemia or thrombocytopenia was observed. A second primary cancer developed in 9 patients (10-year cumulative incidence, 21%). The 10-year non-relapse-related mortality was 18% (14% when deaths related to coronavirus disease 2019 were excluded). Higher CAR-transgene persistence appeared to be associated with long-term response. B-cell aplasia persisted in 44% of patients with a long-term response. CONCLUSIONS: Among patients with heavily pretreated B-cell non-Hodgkin lymphoma, a single infusion of tisagenlecleucel led to decade-long remissions (lymphoma-free survival) in approximately one third of the patients with large B-cell lymphomas and in nearly one half of those with follicular lymphoma. (Funded by the Richard Berman Family Innovations Center in CLL and Lymphomas and others; ClinicalTrials.gov number, NCT02030834.).
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