Shen Junyi, Hu Rong, Lin Anqi, Jiang Aimin, Tang Bufu, Liu Zaoqu, Cheng Quan, Miao Kai, Zhang Jian, Luo Peng
Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
Department of Pharmacy, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China.
EClinicalMedicine. 2024 Jun 20;73:102684. doi: 10.1016/j.eclinm.2024.102684. eCollection 2024 Jul.
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).
美国食品药品监督管理局（FDA）关于嵌合抗原受体T细胞（CAR-T）疗法后T细胞淋巴瘤风险的警示已引起全球关注，但目前仍缺乏CAR-T治疗后第二原发性恶性肿瘤（SPM）的全面概况。
我们从FDA不良事件报告系统（FAERS）和VigiBase数据库（2017 - 2023年）中提取了血液系统恶性肿瘤（HM）患者中具有明确可定义SPM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与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细胞疗法后的SPM包括血液系统恶性肿瘤和实体瘤。在总体和亚组分析中，T细胞淋巴瘤和骨髓增生异常综合征一直被确定为阳性信号。血液系统SPM在CAR-T治疗后发病较早，且年发病率呈上升趋势，而实体瘤表现出延迟出现。接受CAR-T治疗的患者中SPM的发病明显早于未接受治疗的患者。此外，特定年龄特征显示，与CAR-T治疗后的老年人群相比，儿科、青少年和年轻成人人群中SPM的表现更早。
鉴于观察到的SPM年发病率上升情况，当前的SPM概况凸显了对所有CAR-T治疗接受者进行长期安全监测的必要性。针对不同年龄组定制长期SPM筛查可能会加强早期检测和干预策略，最终改善CAR-T治疗接受者随访中的患者预后。
本研究得到了广东省自然科学基金（2018A030313846和2021A1515012593）、广东省科技计划项目（2019A030317020）、国家自然科学基金（81802257、81871859、81772457、82172750、82172811和82260546）、广东省基础与应用基础研究基金（广东 - 广州联合基金）（2022A1515111212）以及广州市科技计划项目（2023A04J1257）的资助。
