美国食品和药物管理局（FDA）于2023年11月发布关于接受嵌合抗原受体T细胞（CAR-T）治疗B细胞恶性肿瘤的患者出现继发性T细胞淋巴瘤的报告，引起了患者的广泛关注、临床医生和科学家。最初，与评估因果关系相关的信息很少，最重要的是，CAR 逆转录病毒或慢病毒载体基因组插入是否有助于肿瘤发生。然而，自那时以来，一些出版物提供了三个案例的临床和分子细节，显示肿瘤细胞中克隆 CAR 载体插入，但没有确凿的证据表明这些插入在致癌转化中发挥了任何作用。此外，还报道了其他几例在肿瘤细胞中未检测到载体的病例。此外，流行病学分析以及机构长期 CAR-T 受体队列研究提供了重要的额外信息，表明 CAR-T 治疗后发生 T 细胞淋巴瘤的风险极低。本综述将总结迄今为止可获得的信息，并回顾相关的先前研究，这些研究表明成熟 T 细胞对插入性肿瘤发生的敏感性较低，并记录了自然 HIV 感染后几乎完全缺乏 T 细胞转化。讨论了可能使接受 CAR-T 细胞治疗的患者易患继发性血液恶性肿瘤的其他因素，包括免疫功能障碍和克隆造血，这些因素可能比插入突变在 CAR 治疗后继发性恶性肿瘤中发挥更大的作用。版权所有 © 2024 美国血液学会。

The United States Food and Drug Administration (FDA) announcement in November 2023 regarding reports of the occurrence of secondary T-cell lymphomas in patients receiving chimeric antigen receptor T-cells (CAR-T) for B-cell malignancies resulted in widespread concern among patients, clinicians and scientists. Little information relevant to assessing causality, most importantly whether CAR retroviral or lentiviral vector genomic insertions contribute to oncogenesis, was initially available. However, since that time several publications have provided clinical and molecular details on three cases showing clonal CAR vector insertions in tumor cells but without firm evidence these insertions played any role in oncogenic transformation. In addition, several other cases have been reported without vector detected in tumor cells. In addition, epidemiologic analyses as well as institutional long-term CAR-T recipient cohort studies provide important additional information suggesting the risk of T-cell lymphomas following CAR-T therapies is extremely low. This review will provide a summary of information available to date, as well as review relevant prior research suggesting a low susceptibility of mature T-cells to insertional oncogenesis and documenting the almost complete lack of T-cell transformation following natural HIV infection. Alternative factors that may predispose patients treated with CAR-T cells to secondary hematologic malignancies, including immune dysfunction and clonal hematopoiesis, are discussed and likely play a greater role than insertional mutagenesis in secondary malignancies post-CAR therapies.Copyright © 2024 American Society of Hematology.