FDA 关于 CAR-T 治疗后 T 细胞淋巴瘤风险的警报引起了全球关注，但缺乏 CAR-T 治疗后第二原发恶性肿瘤（SPM）的全面概况。我们提取了血液恶性肿瘤（HM）的不良事件报告具有 FAERS 和 VigiBase 数据库（2017-2023）中明确定义的 SPM 的患者。使用报告优势比 (ROR) 和调整后的 ROR 进行不成比例分析，以评估 SPM 和 CAR-T 疗法之间的关联。发病时间分析探讨了影响 SPM 表现的因素。CAR T 细胞治疗后的 SPM 包括 HM 和实体瘤。在总体分析和亚组分析中，T 细胞淋巴瘤和骨髓增生异常综合征始终被认为是阳性信号。血液学 SPM 显示发病较早，并且在 CAR-T 治疗后年发病率不断增加，而实体瘤则表现出延迟表现。 CAR-T 接受者的 SPM 发病时间明显早于非接受者。此外，年龄特异性特征揭示了与 CAR-T 治疗后的老年人群相比，儿科、青少年和年轻成年人群更早出现 SPM 表现。当前的 SPM 概况强调了对所有 CAR-T 接受者进行长期安全监测的必要性。观察到 SPM 逐年增加。针对不同年龄组定制长期SPM筛查可以增强早期发现和干预策略，最终改善CAR-T接受者随访中的患者预后。这项工作得到了广东省自然科学基金项目（2018A030313846和2021A1515012593)、广东省科技计划项目(2019A030317020)、国家自然科学基金项目(81802257、81871859、81772457、82172750、82172811和82260546)、广东省基础与应用基础研究基金(顾昂东-广州联合基金）（2022A1515111212）和广州市科技计划项目（2023A04J1257）。© 2024 作者。

The FDA's alerts regarding the T-cell lymphoma risk post CAR-T therapy has garnered global attention, yet a comprehensive profile of second primary malignancies (SPMs) following CAR-T treatment is lacking.We extracted adverse event reports of hematological malignancies (HMs) patients with clearly definable SPMs from the FAERS and VigiBase databases (2017-2023). Disproportionality analysis using reporting odds ratio (ROR) and adjusted ROR was performed to assess associations between SPMs and CAR-T therapy. Time-to-onset analysis explored factors affecting SPM manifestation.SPMs post CAR T-cell therapy include HMs and solid tumors. T-cell lymphoma and myelodysplastic syndromes were consistently identified as positive signals across the overall and subgroup analyses. Hematological SPMs showed earlier onset with increasing annual incidence post CAR-T therapy, whereas solid tumors exhibit delayed manifestation. SPMs in CAR-T recipients had significantly earlier onset than non-recipients. Furthermore, age-specific characteristics reveal earlier SPM manifestations in pediatric, adolescent, and young adult populations compared to older populations post CAR-T therapy.The current SPM profile highlights the necessity of long-term safety monitoring for all CAR-T recipients given the observed yearly increase of SPMs. Customizing long-term SPM screening across different age groups may enhance early detection and intervention strategies, ultimately improving patient outcomes in the follow-up of CAR-T recipients.This work was supported by grants from the Natural Science Foundation of Guangdong Province (2018A030313846 and 2021A1515012593), the Science and Technology Planning Project of Guangdong Province (2019A030317020), the National Natural Science Foundation of China (81802257, 81871859, 81772457, 82172750, 82172811, and 82260546), the Guangdong Basic and Applied Basic Research Foundation (Guangdong-Guangzhou Joint Funds) (2022A1515111212), and the Science and Technology Program of Guangzhou (2023A04J1257).© 2024 The Author(s).