{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T16:04:36Z","timestamp":1789401876695,"version":"build-2803163510"},"reference-count":102,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape of relapsed\/refractory (R\/R) B-cell acute lymphoblastic leukemia (B-ALL), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM); however, a substantial proportion of patients eventually experience disease relapse despite an initial response. This review provides a brief overview of CAR-T cell therapy, including its manufacturing process and associated toxicities, before examining the biological mechanisms underlying post-CAR-T relapse in B-ALL, NHL\u2014particularly large B-cell lymphoma (LBCL)\u2014and MM. We critically review current and emerging strategies to prevent and manage relapse. Strategies for relapse prevention primarily include consolidation approaches, such as allogeneic hematopoietic stem cell transplantation (allo-HSCT), maintenance with targeted agents (e.g., tyrosine kinase inhibitors in Philadelphia chromosome-positive B-ALL), and CAR-T cell reinfusion, whereas relapse management is disease-specific and increasingly incorporates novel therapeutic agents, including bispecific antibodies (BsAbs) and other targeted therapies. However, current evidence remains largely preliminary and is limited by the paucity of randomized prospective trials.<\/jats:p>","DOI":"10.3390\/cells15181660","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T15:19:04Z","timestamp":1789399144000},"page":"1660","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond CAR-T: Preventing and Treating Relapse in B-Cell Haematological Malignancies"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-4703-6280","authenticated-orcid":false,"given":"Martina","family":"Canichella","sequence":"first","affiliation":[{"name":"Division of Hematology, Ospedale S. Eugenio, Piazzale dell\u2019Umanesimo 10, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5228-6491","authenticated-orcid":false,"given":"Elisabetta","family":"Abruzzese","sequence":"additional","affiliation":[{"name":"Division of Hematology, Ospedale S. Eugenio, Piazzale dell\u2019Umanesimo 10, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariagiovanna","family":"Cefalo","sequence":"additional","affiliation":[{"name":"Division of Hematology, Ospedale S. Eugenio, Piazzale dell\u2019Umanesimo 10, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Gianfelici","sequence":"additional","affiliation":[{"name":"Division of Hematology, Ospedale S. Eugenio, Piazzale dell\u2019Umanesimo 10, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Mazzone","sequence":"additional","affiliation":[{"name":"Division of Hematology, Ospedale S. Eugenio, Piazzale dell\u2019Umanesimo 10, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gentiana Elena","family":"Trotta","sequence":"additional","affiliation":[{"name":"Division of Hematology, Ospedale S. Eugenio, Piazzale dell\u2019Umanesimo 10, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Laureana","sequence":"additional","affiliation":[{"name":"Division of Hematology, Ospedale S. Eugenio, Piazzale dell\u2019Umanesimo 10, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Cupelli","sequence":"additional","affiliation":[{"name":"Division of Hematology, Ospedale S. Eugenio, Piazzale dell\u2019Umanesimo 10, 00144 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Ilaria","family":"Del Principe","sequence":"additional","affiliation":[{"name":"Division of Hematology, Ospedale S. Eugenio, Piazzale dell\u2019Umanesimo 10, 00144 Rome, Italy"},{"name":"Department of Biomedicina e Prevenzione, Tor Vergata University, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1056\/NEJMoa1709866","article-title":"Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia","volume":"378","author":"Maude","year":"2018","journal-title":"N. Engl. J. 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