{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:09:24Z","timestamp":1791875364408,"version":"4.3.4"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010154","name":"Fundaci\u00f3n P\u00fablica Andaluza para la Gesti\u00f3n de la Investigaci\u00f3n en Salud de Sevilla","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010154","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Inotuzumab ozogamicin is increasingly being used as bridging therapy (BT) prior to chimeric antigen receptor T-cell (CAR-T) in relapsed\/refractory B-cell acute lymphoblastic leukemia (R\/R ALL), but its impact on CAR-T expansion and clinical outcomes remains controversial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study analyzed 24 R\/R ALL patients receiving tisagenlecleucel after BT (Inotuzumab [n=10] vs. chemotherapy\/steroids [n=14]). CAR-T expansion was monitored via multiparametric flow cytometry at different time-points after infusion, with outcomes assessed by event-free survival (EFS), overall survival, and immunophenotypic profiling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Results indicate that despite lower CAR-T expansion with inotuzumab (median 58.3 vs. 337.7 CAR-T\/\u03bcL; p=0.011), no difference at 12-month EFS was observed (66.7% vs. 64.3%; p=0.648). However, low tumor burden (LTB) at the time of infusion correlated with improved EFS (81.8% vs. 25% high tumor burden (HTB); p=0.019). Remarkably, inotuzumab achieved superior tumor reduction: 80% of HTB patients achieved LTB vs. 28.6% with chemotherapy (p=0.032). Achieving or maintaining LTB significantly improved EFS in 12 months (81.8% and 100% respectively) vs 25% for patients who maintained HTB. Immunophenotyping revealed a higher proportion of CD8+ stem cell memory (SCM) CAR-T cells at peak of expansion in the inotuzumab group (p=0.036). Interestingly, shorter EFS was observed among those patients who presented a lower percentage of SCM CD8+ CAR-T and lower SCM CD8+CARneg\/\u03bcL on 28 days and on 90 days after CAR-T therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Overall, inotuzumab as BT effectively reduces tumor burden but attenuates CAR-T expansion without compromising survival outcomes. As high tumor burden is a dominant driver of relapse and toxicity, the net effect of inotuzumab may be favorable in selected patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1725878","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T05:16:05Z","timestamp":1766034965000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of inotuzumab ozogamicin as bridging therapy and tumor burden in CAR-T therapy for B-acute lymphoblastic 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