{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:09:48Z","timestamp":1794002988785,"version":"4.8.0"},"reference-count":49,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2025,2,1]]},"abstract":"\n Importance<\/jats:title>\n The commercialization of chimeric antigen receptor\u2013T-cell (CAR-T) therapy has changed the landscape of treatment of hematological cancers. 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. However, there has been some recent concern about the risk for second primary cancers (SPCs).<\/jats:p>\n <\/jats:sec>\n \n Observations<\/jats:title>\n Multiple cases of SPCs arising after CAR-T therapy have been reported to the US Food and Drug Administration. Most SPCs have been negative for the chimeric antigen receptor transgene, with rare reports of transgene-positive cancers. This review summarizes the most salient literature on epidemiology and pathobiology of SPCs after CAR-T therapy. Additionally, a discussion is provided on potential mitigation strategies for SPCs after CAR-T therapies.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n The results of this review suggest that there are limited data to suggest that inadvertent transgene insertion is associated with SPCs in the post\u2013CAR-T setting. Nonetheless, evidence-based practical solutions and scientific strategies for risk mitigation can be implemented. 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. 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoncol.2024.5412","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T11:00:45Z","timestamp":1734001245000},"page":"174","source":"Crossref","is-referenced-by-count":27,"title":["Second Primary Cancer After Chimeric Antigen Receptor\u2013T-Cell Therapy"],"prefix":"10.1001","volume":"11","author":[{"given":"Shyam A.","family":"Patel","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, Center for Clinical and Translational Science, UMass Chan Medical School, Worcester"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay Y.","family":"Spiegel","sequence":"additional","affiliation":[{"name":"Sylvester Comprehensive 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