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Preclinical studies demonstrated that Bruton tyrosine kinase inhibitor (BTKi) improved the efficacy of CART19 therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We designed this open\u2010label, non\u2010randomized pragmatic clinical trial. The primary end point was safety, and the secondary end point was clinical response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirty\u2010seven patients included were assigned to CART19 monotherapy (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200924) or CART19 combined with BTKi (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200913) group on their own accord. Grade 1\u20132 and grade 3 cytokine release syndrome occurred in 43.2% and 2.7% of patients, respectively. One patient experienced grade 3 neurotoxicity. The most common severe adverse events were hematological toxicities, including neutropenia (in 97.3% of patients), thrombocytopenia (in 40.5%), and anemia (in 43.2%). The adverse effects were comparable between the two groups. The best objective response rates were 84.6% vs. 66.7% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05) in patients with and without BTKi, and the best complete response rates were 61.5% vs. 25.0% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). The combination of BTKi significantly prolonged the overall survival but did not affect the progression\u2010free survival or the duration of response. T cells of patients treated with BTKi were predisposed to early differentiation and less exhaustion 3\u2009months after CART19 infusion. Single\u2010cell RNA sequencing analysis demonstrated that T cells were dysfunctional at relapse.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>BTKi combined with CART19 induced better outcomes with good safety profiles in patients with BCL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      identifier: NCT05020392\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71321","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T12:09:41Z","timestamp":1761134981000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>BTK<\/scp>\n                    Inhibitor Synergizes With\n                    <scp>CD19<\/scp>\n                    \u2010Targeted Chimeric Antigen Receptor\u2010T Cells in Patients With Relapsed or Refractory B\u2010Cell Lymphoma: An Open\u2010Label Pragmatic Clinical Trial"],"prefix":"10.1002","volume":"14","author":[{"given":"Wenjing","family":"Luo","sequence":"first","affiliation":[{"name":"Institute of Hematology Union Hospital, Tongji Medical College, Huazhong University of Science and Technology  Wuhan China"},{"name":"Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease  Wuhan China"},{"name":"Key Laboratory of Biological Targeted Therapy (Huazhong University of Science and 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