{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T18:38:50Z","timestamp":1767206330555,"version":"build-2238731810"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"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":"\n Objective<\/jats:title>\n This study aimed to evaluate the efficacy and safety of rituximab, methotrexate, cytarabine with or without ibrutinib in newly diagnosed primary central nervous system lymphoma (PCNSL) and explore the correlation between efficacy and genomic alterations.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n From March 2013 to October 2022, data from 88 patients with newly diagnosed PCNSL were retrospectively collected and analyzed. Fifty-nine patients received rituximab, methotrexate and cytarabine (RMA, group A), and twenty-nine patients received the same RMA combined with ibrutinib (RMA + Ibrutinib, group B).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n At a median follow-up of 27.7 months, the complete response rate (CRR), overall response rate (ORR) and overall survival (OS) in group B superior to group A (41.4% versus 16.9% for CRR, P=0.013; 86.2% versus 59.3% for ORR,\n P<\/jats:italic>\n =0.011; P=0.036 for OS). The ORR, progression-free survival (PFS) and OS of RMA + ibrutinib +deep lesions (group C) were better than those of RMA + deep lesions (group D) (\n P<\/jats:italic>\n =0.027 for ORR,\n P=<\/jats:italic>\n 0.046 for PFS,\n P<\/jats:italic>\n =0.004 for OS). Patients in group B had no more toxicities than those in group A and the most common adverse events in the two groups were primarily grade 1-2. Sequencing of tumor tissues from 22 patients showed that\n MYD88<\/jats:italic>\n mutations were the most frequent genetic alterations, two patients with\n CARD11<\/jats:italic>\n mutation did not respond to treatment and three patients without an\n MYD88<\/jats:italic>\n or\n CD79B<\/jats:italic>\n had response after treatment.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n RMA in combination with ibrutinib regimen improved response rates and survival in newly diagnosed PCNSL with no serious adverse effects. Mutations in\n CARD11<\/jats:italic>\n gene may provide directions for patients to select targeted drugs.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1579483","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T01:27:40Z","timestamp":1747877260000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical outcomes of newly diagnosed PCNSL treated with rituximab-methotrexate-cytarabine with or without ibrutinib: a retrospective study"],"prefix":"10.3389","volume":"16","author":[{"given":"Wenhua","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifei","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihua","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengzi","family":"Qian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiyong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xudong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lanfang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianhuo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huilai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1038\/s41572-023-00439-0","article-title":"Primary central nervous system lymphoma","volume":"9","author":"Ferreri","year":"2023","journal-title":"Nat Rev Dis Primers"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2011.169","article-title":"Modern concepts in the biology, diagnosis, differential diagnosis and treatment of primary central nervous system lymphoma","volume":"25","author":"Deckert","year":"2011","journal-title":"Leukemia"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.03.036","article-title":"Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96-07","volume":"21","author":"Batchelor","year":"2003","journal-title":"J Clin Oncol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1093\/neuonc\/noac196","article-title":"European Association of Neuro-Oncology (EANO) guidelines for treatment of primary central nervous system lymphoma (PCNSL)","volume":"25","author":"Hoang-Xuan","year":"2023","journal-title":"Neuro Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.128","article-title":"Improved survival in primary central nervous system lymphoma up to age 70 only: a population-based study on incidence, primary treatment and survival in the Netherlands, 1989-2015","volume":"31","author":"van der Meulen","year":"2017","journal-title":"Leukemia"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nox187","article-title":"The elderly left behind-changes in survival trends of primary central nervous system lymphoma over the past 4 decades","volume":"20","author":"Mendez","year":"2018","journal-title":"Neuro Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01582-5","article-title":"Long-term efficacy, safety and neurotolerability of MATRix regimen followed by autologous transplant in primary CNS lymphoma: 7-year results of the IELSG32 randomized trial","volume":"36","author":"Ferreri","year":"2022","journal-title":"Leukemia"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16451","article-title":"Induction therapy with the MATRix regimen in patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system - 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