{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T06:59:27Z","timestamp":1793257167147,"version":"4.5.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,24]],"date-time":"2022-11-24T00:00:00Z","timestamp":1669248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004731","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>Relapsed or refractory diffuse large B-cell lymphoma (R\/R DLBCL) has poor clinical outcomes when treated with conventional salvage chemotherapy. Monotherapy using zanubrutinib, a selective Bruton\u2019s tyrosine kinase (BTK) inhibitor, has achieved modest antitumor effect in R\/R DLBCL. Here we aimed to evaluate the efficacy and safety of zanubrutinib plus salvage chemotherapy in R\/R DLBCL patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively reviewed R\/R DLBCL patients who were administered with zanubrutinib plus salvage chemotherapy in our center between January, 2019 and December, 2021. Targeted panel sequencing of 11 lymphoma-related genes was performed on 8 patients with poor responses to zanubrutinib-based chemotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      27 R\/R DLBCL patients were enrolled. Median age at this study was 59 years (range, 15-72). The best overall response rate (ORR) was 74.1% and complete remission rate was 33.3%. With a median follow-up of 11 months (range, 1-17), the median progression-free survival (PFS) was 8.1 months, and the overall survival (OS) was not achieved. The most common grade-3\/4 adverse events were neutropenia (70.4%), thrombocytopenia (66.7%), and febrile neutropenia (33.3%). In multivariate analysis, early treatment and overall response after chemotherapy were independent favorable prognostic factors for PFS. Overall response after chemotherapy was an independent favorable factor for OS. Among the 8 patients with poor response to zanubrutinib-based treatment, the majority of patients had\n                      <jats:italic>NOTCH2<\/jats:italic>\n                      mutations (n=8, 100%) and\n                      <jats:italic>TP53<\/jats:italic>\n                      mutations (n=7, 87.5%). However, these patients achieved an ORR of 75% at 3 months after CD19-CAR-T cell therapy (including 4 cases of complete remission and 2 cases of partial remission). With a median follow-up of 9 months from CAR-T cell infusion (range, 1-16 months), the median PFS was 14.5 months, and the median OS was not reached.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>With high efficacy and manageable tolerability, zanubrutinib plus salvage chemotherapy may be a potential treatment option for R\/R DLBCL. CAR-T cell therapy may be a priority strategy for these poor responders to BTKi-based treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2022.1015081","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T23:40:04Z","timestamp":1669246804000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Zanubrutinib plus salvage chemotherapy for relapsed or refractory diffuse large B-cell 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