{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T06:10:40Z","timestamp":1775542240565,"version":"3.50.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Relapsed or refractory (R\/R) non\u2013germinal center B-cell\u2013like (non-GCB) diffuse large B-cell lymphoma (DLBCL) shows poor clinical outcomes. Bruton tyrosine kinase (BTK) inhibitors have established therapeutic activity by targeting B-cell receptor signaling, with promising results in treating DLBCL. The monotherapy of zanubrutinib, a selective BTK inhibitor, or second-line salvage chemotherapy has shown limited efficacy in patients with R\/R DLBCL. Thus, the present study evaluated the efficacy and safety of zanubrutinib-combined therapy in heavily treated patients with non-GCB DLBCL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study consists of 27 heavily treated patients with non-GCB DLBCL who received zanubrutinib-combined therapy between January 2021 and February 2024 in Shanghai Tongji Hospital and Zhejiang Second Affiliated Hospital. Efficacy outcomes included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), whereas safety outcomes included incidence of adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of all the 27 enrolled patients\u2019 baseline,24 patients (88.9%) showed a high IPI score (\u22653), 23 patients (85.2%) had a high proliferation score (Ki 67\u226580%) and 20 patients (74.1%) were heavily treated with \u22653 lines of previous treatments. The ORR in all patients was 74.1% (95%CI, 53.7%-88.9%), the partial response (PR) was 66.7% (95%CI, 46.0%-83.5%). With a median follow-up of 36.6 months, the median PFS was 10.6 months (95%CI 7.3-14) and median OS was 19.6 months (95%CI 12.3-not reached). The grade \u22653 hematologic toxicities included neutropenia (85.1%, 23\/27) and thrombocytopenia (37%, 10\/27). The grade \u22653 nonhematologic AEs were hypokalemia (11.1%, 3\/27) and pulmonary infection (11.1%, 3\/27). No treatment-related deaths occurred. Subgroups stratified by gender, age, and presence\/absence of extranodal lesions all maintained an ORR of over 70%. The efficacy of the combined therapy seemed to be not affected by most baseline characteristics and was associated with high response even in high-risk subgroups. Of all the evaluated 27 patients, 2 patients got complete response (CR) received autologous stem cell transplantation and lenalidomide maintenance therapy respectively. 19 patients got no CR were bridged to CD19 chimeric antigen receptor (CAR)-T cell therapy, while the other 6 patients received additional salvage chemotherapy. In the CAR-T cohort, the ORR was 89.5% (95%CI: 67.0%~98.2%) and CR was 57.9% (95%CI: 34.5%~78.9%), the median PFS was 14 months (95% CI: 5.2-37.9) and median OS was 27.7 months (95% CI: 10.1- not reached). The CAR-T group was associated with improved overall survival relative to the non-CAR-T group (HR\u00a0=\u00a00.21, 95% CI: 0.05\u20130.79, P\u00a0=\u00a00.02). In the landmark analysis, the survival probability of CART group was 80% at 12 months post-landmark, the non-CAR-T group exhibited an earlier initial drop with survival decreasing to 57.1% at 12 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Zanubrutinib-combined therapy was effective and safe for the treatment of heavily treated patients with non-GCB DLBCL. It offers a promising treatment option and serving as an effective bridge to CAR-T therapy, with manageable toxicity. Future prospective studies with larger cohorts are needed to validate these findings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1806191","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T05:28:29Z","timestamp":1775539709000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Zanubrutinib-based regimen as the salvage or bridging treatment of CART therapy in relapsed or refractory, non-germinal center B-cell\u2013like diffuse large B-cell lymphoma: a retrospective multicenter cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Yan","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Hematology, Tongji Hospital of Tongji University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiguang","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Hematology, Tongji Hospital of Tongji University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Hematology, Tongji Hospital of Tongji University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianggui","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Second Affiliated Hospital, College of Medicine, Zhejiang University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology, Tongji Hospital of Tongji University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbin","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Second Affiliated Hospital, College of Medicine, Zhejiang University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aibin","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Tongji Hospital of Tongji University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-06-2508","article-title":"Lymphoma incidence patterns by WHO subtype in the United States 1992-2001","volume":"107","author":"Morton","year":"2006","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","first-page":"66","DOI":"10.4103\/2278-330X.126531","article-title":"Management of relapsed-refractory diffuse large B cell lymphoma","volume":"3","author":"Raut","year":"2014","journal-title":"South Asian J 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