■FDA关于CAR-T疗法后T细胞淋巴瘤风险的警报引起了全球关注,然而,目前尚缺乏CAR-T治疗后第二原发恶性肿瘤(SPM)的综合资料.
■我们从FAERS和VigiBase数据库(2017-2023)中提取了具有明确定义的SPM的血液恶性肿瘤(HM)患者的不良事件报告。使用报告比值比(ROR)和调整后的ROR进行不成比例分析,以评估SPM和CAR-T治疗之间的关联。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HMs和实体瘤。T细胞淋巴瘤和骨髓增生异常综合征在总体和亚组分析中被一致地鉴定为阳性信号。血液学SPM显示,CAR-T治疗后发病较早,年发病率增加,而实体瘤表现为延迟表现。CAR-T接受者的SPM明显比非接受者早。此外,年龄特异性特征揭示了儿科早期的SPM表现,青春期,与CAR-T治疗后的老年人群相比,年轻人群。
■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,因为观察到SPM的逐年增加。在不同年龄段进行长期SPM筛查可能会增强早期发现和干预策略,在CAR-T受者的随访中最终改善患者预后.
■这项工作得到了广东省自然科学基金(2018A030313846和2021A1515012593)的资助,广东省科技规划项目(2019A030317020),国家自然科学基金(81802257,81871859,81772457,82172750,82172811,82260546),广东省基础与应用基础研究基金会(粤广联合基金)(2022A1515111212),广州市科学技术计划(2023A04J1257)。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).