Second Primary Cancer After Chimeric Antigen Receptor-T-Cell Therapy: A Review.

Numerous studies from the early 2000s paved the way for cell-based targeted therapeutics, which have been established as practice-changing therapies in lymphoma, leukemia, and multiple myeloma.

21世纪初的众多研究为基于细胞的靶向治疗铺平了道路，这些治疗已在淋巴瘤、白血病和多发性骨髓瘤中被确立为改变实践的疗法。

However, there has been some recent concern about the risk for second primary cancers (SPCs).

然而，最近有一些关于第二原发癌（SPCs）风险的担忧。

observations

Multiple cases of SPCs arising after CAR-T therapy have been reported to the US Food and Drug Administration.

美国食品药品监督管理局已经报告了多例CAR-T疗法后出现的SPCs病例。

Most SPCs have been negative for the chimeric antigen receptor transgene, with rare reports of transgene-positive cancers.

大多数继发性恶性肿瘤对嵌合抗原受体转基因呈阴性，偶尔有转基因阳性癌症的报道。

This review summarizes the most salient literature on epidemiology and pathobiology of SPCs after CAR-T therapy.

本综述总结了关于CAR-T疗法后继发性恶性肿瘤流行病学和病理生物学的最新文献。

Additionally, a discussion is provided on potential mitigation strategies for SPCs after CAR-T therapies.

此外，本综述还提供了关于CAR-T疗法后继发性恶性肿瘤（SPCs）潜在缓解策略的讨论。

conclusions_and_relevance

The results of this review suggest that there are limited data to suggest that inadvertent transgene insertion is associated with SPCs in the post-CAR-T setting.

本综述的结果表明，目前有限的数据表明意外的转基因插入与CAR-T疗法后继发性恶性肿瘤（SPCs）之间存在关联。

Nonetheless, evidence-based practical solutions and scientific strategies for risk mitigation can be implemented.

然而，可以实施基于证据的实际解决方案和科学策略以降低风险。

These include optimization of T-cell manufacturing, application of safer synthetic immunobiology, and implementation of high-fidelity genomic testing, including baseline screening for clonal hematopoiesis.

这包括T细胞制造的优化、更安全的合成免疫生物学的应用，以及实施高保真度的基因组测试，包括对克隆性造血的基线筛查。

These strategies may inform optimal design of the next generation of CAR-T products that confer minimal risk for SPCs such that the risk-benefit profile remains favorable to proceed with CAR-T administration for eligible patients.

这些策略可能为下一代CAR-T产品的最佳设计提供信息，以最小化SPCs的风险，确保风险-效益比对符合条件的患者进行CAR-T治疗仍然有利。