{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T10:13:51Z","timestamp":1771496031307,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>CD19-directed chimeric antigen receptor (CAR) T-cell therapies have been instrumental in improving outcomes of refractory or relapsed B-cell malignancies. However, there have been safety concerns due to recent reports of second primary malignancies (SPMs) related to CAR T-cell therapies. We reviewed articles from Embase, PubMed, and Cochrane Library records and included SPM case reports as well as cohort studies. Across published cohorts, secondary cutaneous or peripheral T-cell lymphoma (PTCL) after diffuse large B-cell lymphomas (DLBCLs) have been reported at low incidence (generally in the low single-digit percentage range). While CAR T-cell therapy is associated with these rare secondary malignancies and lineage-switch events primarily described in acute leukemia, they are clinically significant and have resulted in increased surveillance. The currently available evidence suggests that most secondary malignancies after CAR T-cell therapy are due to background risk and prior treatment exposures rather than direct CAR T-cell therapy induced oncogenesis. However, rare CAR T-cell therapy-associated second primary T-cell malignancies have been reported. To properly define incidence, mechanisms, and risk factors for CAR T-cell therapy-associated malignancies, continued prospective registry follow-up and additional research will be needed.<\/jats:p>","DOI":"10.3390\/cancers18040678","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T08:51:09Z","timestamp":1771491069000},"page":"678","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["At the Crossroads of Lineage: Secondary Malignancies After CAR-Based Immunotherapy"],"prefix":"10.3390","volume":"18","author":[{"given":"Logan","family":"Lorentzen","sequence":"first","affiliation":[{"name":"Reno School of Medicine, University of Nevada, Reno, NV 89557, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mazie","family":"Tsang","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Mayo Clinic Arizona, Phoenix, AZ 85054, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8249-4128","authenticated-orcid":false,"given":"Talal","family":"Hilal","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Mayo Clinic Arizona, Phoenix, AZ 85054, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8915-3163","authenticated-orcid":false,"given":"Allison","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Mayo Clinic Arizona, Phoenix, AZ 85054, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9060-8911","authenticated-orcid":false,"given":"Javier","family":"Munoz","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Mayo Clinic Arizona, Phoenix, AZ 85054, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/jncimonographs\/lgu010","article-title":"Medical history, lifestyle, family history, and occupational risk factors for diffuse large B-cell lymphoma: The InterLymph Non-Hodgkin Lymphoma Subtypes Project","volume":"48","author":"Cerhan","year":"2014","journal-title":"J. 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