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Here we report the persistence and characteristics of 4-1BB-costimulated anti-CD19 CAR T cells (CART19) up to 10 years after infusion in 38 patients with non-Hodgkin lymphoma. Beyond year five, the\n                    <jats:italic>CAR19<\/jats:italic>\n                    transgene was detectable in five of eight long-term responders (7.0\u201310.1 years), with three patients maintaining B cell aplasia, which is consistent with sustained functional activity. In one patient with a progression-free survival of 10.1 years, CART19 cells comprised 1.2% of circulating T cells 9.3 years after infusion. Long-term persisting CART19 cells exhibited a predominant double-negative (CD4\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD8\n                    <jats:sup>\u2212<\/jats:sup>\n                    ), effector-memory-like phenotype associated with increased aerobic metabolism and T cell activation programs. Longitudinal profiling revealed a progressive transition from CD8\n                    <jats:sup>+<\/jats:sup>\n                    to double-negative CAR T cells over time. Persisting CART19 shared transcriptional features with long-term CAR T cells described in acute and chronic leukemias. T cell receptor sequencing demonstrated oligoclonal persistence at 9.3 years, with a dominant clone (70% of CART19 cells) already detectable at low frequency (&lt;0.1%) at day 14. Lentiviral integration-site analysis identified a predominant integration within PACS1 without evidence of known drivers of CAR T cell expansion. These findings demonstrate that CART19 cells can persist for more than 10 years in lymphoma and identify phenotypic, transcriptional and clonal features associated with exceptionally long-term persistence. ClinicalTrials.gov registration:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT02030834\" ext-link-type=\"uri\">NCT02030834<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1038\/s41591-026-04578-1","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:02:41Z","timestamp":1786352561000},"page":"3276-3287","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Decade-long persistence of CD19 CAR T cells in B cell lymphomas"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6505-0194","authenticated-orcid":false,"given":"Luca","family":"Paruzzo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0324-5367","authenticated-orcid":false,"given":"Emeline 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Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 22, 1403\u20131415 (2021).","journal-title":"Lancet Oncol."},{"key":"4578_CR7","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/s41591-021-01622-0","volume":"28","author":"NH Fowler","year":"2022","unstructured":"Fowler, N. H. et al. Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial. Nat. Med. 28, 325\u2013332 (2022).","journal-title":"Nat. Med."},{"key":"4578_CR8","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/S1470-2045(21)00591-X","volume":"23","author":"CA Jacobson","year":"2022","unstructured":"Jacobson, C. A. et al. Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. 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S.D.N. received research support from Takeda, Roche, Loxo\/Lilly, Ono, Pierre Fabre, Caribou Biosciences; he was a Data and Safety Monitoring Board (DSMB) member for Merck; and he was a consultant for Genmab and Abbvie. J.S. received research funding from Incyte, Merck and TG Therapeutics; reports consultancy for, and having received research funding from, Bristol Myers Squibb, Seagen, Pharmacyclics and AstraZeneca; and reports consultancy for ADC Therapeutics, Adaptive, Atara, Genmab and Imbrium. J.D.L. received research funding from Curis, Takeda and Triphase, and served on the Board of Directors, advisory committees and Data Safety Monitoring Board for Incyte, ADCT, Karyopharm and Morphosis. J.A.F. is a member of the Scientific Advisory Boards of Cartography Bio and Shennon Biotechnologies and has patents, royalties and other intellectual property. D.L.S. is cofounder of Verismo Therapeutics and Vetigenics. D.L.S. is an inventor on patents or patent applications licensed to Verismo Therapeutic, Vetigenics and Chimeric Therapeutics, and may receive license revenue from such licenses. D.L.S. and the University of Pennsylvania have patents pending or issued related to the use of gene modification in T cells for adoptive T cell therapy. J.J. serves as a consultant for BlueWhale Bio and is named as an inventor on patents related to CAR T cells. D.L.P. declares research funding from Novartis and Bristol Myers Squibb, membership on an entity\u2019s Board of Directors (National Marrow Donor Program), and advisory committee or honoraria from Novartis, Kite\/Gilead, Angiocrine, Mirror Biologics, Sana Biotechnology and Verismo. He is a current equity holder for Genentech and has patents and royalties from Novartis and Tmunity\/Kite. B.L.L. sits on the Scientific Advisory Boards of Avectas, BioOra, Cellula, Immuneel, Immusoft, Ori Biotech, Oxford Biomedica, Quell Therapeutics, Thermo Fisher Pharma Services and UTC Therapeutics. He is a consultant for BioMerieux, the Ludwig Institute for Cancer Research and a cofounder and equity holder for Tmunity Therapeutics (acquired by Kite) and Capstan Therapeutics (acquired by Abbvie). He has royalties from the University of Pennsylvania intellectual property licensed to Novartis. He sits on the board of Directors of Alliance for Cancer Gene Therapy. C.H.J. is a cofounder of Tmunity, and is a scientific cofounder and holds equity in Capstan Therapeutics, Dispatch Biotherapeutics and Bluewhale Bio. C.H.J. serves on the board of AC Immune and is a scientific adviser to BluesphereBio, Cabaletta, Carisma, Cartography, Cellares, Cellcarta, Celldex, Danaher, Decheng, ImmuneSensor, Kite, Poseida, Verismo, Viracta, Vittoria Bio and WIRB-Copernicus group. C.H.J. is an inventor on patents or patent applications licensed to the Novartis Institutes of Biomedical Research and Kite, and may receive license revenue from such licenses. C.H.J. and the University of Pennsylvania have patents pending or issued related to the use of gene modification in T cells for adoptive T cell therapy. M.R. holds patents related to CAR T cell immunotherapy. M.R. has consulted for Bristol Myers Squibb, AbbVie, Guidepoint, G.L.G., viTToria Biotherapeutics, Acera, MODeX, Lumicks, Biocartis, CytoART and AbClon. M.R. receives research funding from viTToria biotherapeutics and AbClon. M.R. is the scientific founder of viTToria biotherapeutics. S.J.S. served as a consultant to AstraZeneca, BeiGene, Celgene, Genentech, Genmab, Fate Therapeutics, Roche, Incyte, Juno Therapeutics, Legend Biotech, Loxo Oncology, MorphoSys, Mustang Biotech, Nordic Nanovector, Novartis and Regeneron; has received research funding from AbbVie, Adaptive Biotechnologies, Celgene, DTRM, Genentech, Roche, Juno Therapeutics, Merck, Novartis, Incyte, Pharmacyclics and and TG Therapeutics; has received honoraria from Celgene and Novartis; and holds patents related to CD19 CAR T cells and autologous costimulated T cells. The other authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}