{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:48:27Z","timestamp":1790938107532,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T00:00:00Z","timestamp":1767484800000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Primary central nervous system lymphoma (PCNSL) is an aggressive, immune\u2010privileged, large B\u2010cell lymphoma with limited frontline treatment options.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study was\u00a0an open\u2010label, single\u2010arm, phase 1\/2 trial evaluating orelabrutinib combined with an anti\u2013programmed cell death protein\u20101 (PD\u20101) antibody and a non\u2010methotrexate chemotherapeutic agent (fotemustine) in patients with newly diagnosed PCNSL (ClinicalTrials.gov identifier NCT04831658). Orelabrutinib was tested at three dose levels (100, 150, and 200 mg), and the recommended phase 2 dose was determined as 150 mg. In phase 2, patients received orelabrutinib 150 mg orally once daily, a PD\u20101 inhibitor 200 mg intravenously on day 1, and fotemustine 100 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      intravenously on day 2 every 21 days for six cycles. The primary endpoint was the objective response rate.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>From February 2021 to October 2023, 31 patients (median age, 62 years; age range, 37\u201370 years) were treated, and 27 were evaluable for efficacy. The objective response rate was 85.2% (complete response, 66.7%; partial response, 18.5%). The median progression\u2010free survival was 9.4 months (95% confidence interval, 5.4\u201313.4 months), and the median overall survival was 22.8 months (95% confidence interval, 1.1\u201344.5 months). The 1\u2010year and 2\u2010year overall survival rates were 68.0% and 48.0%, respectively. The most common grade 3\/4 adverse events were thrombocytopenia (45.2%), pulmonary infection (38.7%), and leukopenia (25.8%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Orelabrutinib combined with PD\u20101 blockade and fotemustine demonstrated high antitumor activity with manageable toxicity, supporting its potential as a frontline regimen for PCNSL.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.70247","type":"journal-article","created":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T10:02:06Z","timestamp":1767520926000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A first\u2010line regimen combining Bruton's tyrosine kinase and programmed cell death protein\u20101 inhibitors with chemotherapy excluding methotrexate achieves high response rates in primary central nervous system lymphoma"],"prefix":"10.1002","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8778-2163","authenticated-orcid":false,"given":"Wanyue","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaorui","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Zhengzhou University  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Zhengzhou University  Zhengzhou 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