Ten-Year Outcomes after CAR T-Cell Therapy for B-Cell Lymphomas.

Long-term results and curative potential remain uncertain.

长期疗效和治愈潜力仍然不确定。

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.

我们对38名复发或难治性B细胞非霍奇金淋巴瘤患者（包括24名大B细胞淋巴瘤患者和14名滤泡性淋巴瘤患者）进行了长期疗效评估，这些患者接受了CTL019（现称tisagenlecleucel）治疗 - 自体T细胞表达CD19导向的4-1BB共刺激嵌合受体。

Lymphoma-free survival was defined as the time from the tisagenlecleucel infusion to relapse or lymphoma-related death.

无淋巴瘤生存期被定义为从tisagenlecleucel输注到复发或与淋巴瘤相关的死亡的时间。

The incidenceof non-relapse-related death and second primary cancer was estimated with the Aalen-Johansen method.

使用Aalen-Johansen方法估计了非复发相关死亡和第二原发癌的发病率。

The data-cutoff date was October 1, 2025.

数据截止日期为2025年10月1日。

Results

At a median follow-up of 10.1 years (range, 7.9 to 11.5), no relapses had occurred beyond 5.4 years.

在中位随访时间为10.1年（范围，7.9至11.5年）的情况下，没有复发发生在5.4年之后。

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.

在患有大B细胞淋巴瘤的患者中，10年的淋巴瘤无病生存率为32%（95%置信区间[CI]，14至51），而在患有滤泡性淋巴瘤的患者中，该比率为47%（95% CI，20至71）。

In an analysis that included deaths from any cause, the 10-year progression-free survivalwas 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 survivalwas 17% (95% CI, 5 to 34) and 50% (95% CI, 23 to 72), respectively.

在一项包括任何原因导致的死亡的分析中，大B细胞淋巴瘤患者的10年无进展生存率为17%（95%置信区间，5至34），滤泡性淋巴瘤患者为29%（95%置信区间，9至52）；10年总生存率分别为17%（95%置信区间，5至34）和50%（95%置信区间，23至72）

Persistent grade 2 or 3 neutropenia occurred in 2 patients (5%); no late anemia or thrombocytopenia was observed.

2名患者（5%）出现持续的2级或3级中性粒细胞减少症；未观察到晚期贫血或血小板减少症。

A second primary cancer developed in 9 patients (10-year cumulative incidence, 21%).

9名患者发生了第二原发癌（10年累积发生率为21%）。

The 10-year non-relapse-related mortality was 18% (14% when deaths related to coronavirus disease 2019 were excluded).

10年非复发相关死亡率为18%（排除与2019冠状病毒病相关的死亡后为14%）。

Higher CAR-transgene persistence appeared to be associated with long-term response.

较高的CAR转基因持续性似乎与长期反应相关。

B-cell aplasia persisted in 44% of patients with a long-term response.

44%的长期反应患者中持续存在B细胞减少症。

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.

在经过重度预处理的B细胞非霍奇金淋巴瘤患者中，单次输注tisagenlecleucel导致了大约三分之一的大B细胞淋巴瘤患者和近一半的滤泡性淋巴瘤患者实现了长达十年的缓解（无淋巴瘤生存期）。

(Funded by the Richard Berman Family Innovations Center in CLL and Lymphomas and others; ClinicalTrials.gov number, NCT02030834.).

(该研究由Richard Berman家族CLL和淋巴瘤创新中心及其他机构资助；ClinicalTrials.gov编号，NCT02030834。)