第二次主要恶性肿瘤的表征在CAR T细胞疗法：来自FAERS和VIGIBASE的两个全球药物守护数据库中的现实世界见解
Characterization of second primary malignancies post CAR T-cell therapy: real-world insights from the two global pharmacovigilance databases of FAERS and VigiBase
影响因子:10.00000
分区:医学1区 Top / 医学：内科1区
发表日期:2024 Jul
作者:
Junyi Shen, Rong Hu, Anqi Lin, Aimin Jiang, Bufu Tang, Zaoqu Liu, Quan Cheng, Kai Miao, Jian Zhang, Peng Luo
摘要
FDA关于CAR-T疗法的FDA警报引起了全球关注，但缺乏CAR-T治疗后第二次初级恶性肿瘤（SPMS）的全面概况。我们从FAERS和VIGIBASE DATABASES（2017-2023）中提取了血液学恶性肿瘤（HMS）患者的不良事件报告（HMS）患者。使用报告优势比（ROR）和调整后的ROR进行了不成比例分析，以评估SPMS与CAR-T治疗之间的关联。发出时间分析探讨了影响SPM表现的因素。SPMSCAR T细胞疗法包括HMS和实体瘤。 T细胞淋巴瘤和骨髓增生性综合征始终被鉴定为整体和亚组分析的正信号。血液学SPMS早于CAR-T治疗后年度发病率较早，而实体瘤表现出延迟的表现。 CAR-T受体中的SPMS比非接收者明显早得多。此外，与CAR-T治疗后老年人相比，小儿，青少年和年轻人种群中的SPM表现早于小儿，青少年和年轻人的早期特征。当前的SPM概况强调了所有CAR-T受体的长期安全监控的必要性，因为SPMS的年度增加了所有CAR-T受体。定制不同年龄段的长期SPM筛查可能会增强早期检测和干预策略，最终改善了CAR-T接收者的随访中的患者结果。这项工作得到了广东自然科学基金会（2018a03030313846和2021a15151501593）的赠款的支持。中国国家自然科学基金会（81802257，81871859，81772457，81772750，82172750，82172811和82260546），广东基本和应用基础研究基金会（Guangdong-Guangzhou联合基金） （2023A04J1257）。
Abstract
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).