肿瘤细胞治疗研究
英文原题：Characterization of second primary malignancies post CAR T-cell therapy: real-world insights from the two global pharmacovigilance databases of FAERS and VigiBase.
Characterization of second primary malignancies post CAR T-cell therapy: real-world insights from the two global pharmacovigilance databases of FAERS and VigiBase.
当前的 SPM 特征凸显出，鉴于观察到的 SPM 逐年增加，对所有 CAR-T 接受者进行长期安全性监测十分必要。
背景：美国FDA关于CAR-T治疗后T细胞淋巴瘤风险的警示引起全球关注，但CAR-T后第二原发恶性肿瘤（SPM）尚缺乏全面特征描述。方法：研究提取2017至2023年FAERS和VigiBase中血液恶性肿瘤患者可明确判定的SPM不良事件报告，采用报告比值比及校正分析关联，并评估发生时间影响因素。结果：CAR-T后SPM包括血液恶性肿瘤和实体瘤；T细胞淋巴瘤及骨髓增生异常综合征在总体和亚组分析中均为稳定阳性信号。血液系统SPM发生时间较早，且随CAR-T应用年度增加而增加；实体瘤出现较迟。CAR-T患者SPM发生时间显著早于未接受者；儿童、青少年和青年患者较老年患者发病更早。结论：观察到SPM逐年增加，所有CAR-T接受者均需长期安全监测。按年龄制定长期筛查方案有助于早期发现和干预，改善随访结局。
BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: 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).
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