{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:53:40Z","timestamp":1790963620841,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T00:00:00Z","timestamp":1593043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013170","name":"Ono Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013170","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The safety, tolerability, efficacy, and pharmacokinetics of tirabrutinib, a second-generation, highly selective oral Bruton\u2019s tyrosine kinase inhibitor, were evaluated for relapsed\/refractory primary central nervous system lymphoma (PCNSL).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with relapsed\/refractory PCNSL, Karnofsky performance status \u226570, and normal end-organ function received tirabrutinib 320 and 480 mg once daily (q.d.) in phase I to evaluate dose-limiting toxicity (DLT) within 28 days using a 3 + 3 dose escalation design and with 480 mg q.d. under fasted conditions in phase II.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Forty-four patients were enrolled; 20, 7, and 17 received tirabrutinib at 320, 480, and 480 mg under fasted conditions, respectively. No DLTs were observed, and the maximum tolerated dose was not reached at 480 mg. Common grade \u22653 adverse events (AEs) were neutropenia (9.1%), lymphopenia, leukopenia, and erythema multiforme (6.8% each). One patient with 480 mg q.d. had grade 5 AEs (pneumocystis jirovecii pneumonia and interstitial lung disease). Independent review committee assessed overall response rate (ORR) at 64%: 60% with 5 complete responses (CR)\/unconfirmed complete responses (CRu) at 320 mg, 100% with 4 CR\/CRu at 480 mg, and 53% with 6 CR\/CRu at 480 mg under fasted conditions. Median progression-free survival was 2.9 months: 2.1, 11.1, and 5.8 months at 320, 480, and 480 mg under fasted conditions, respectively. Median overall survival was not reached. ORR was similar among patients harboring CARD11, MYD88, and CD79B mutations, and corresponding wild types.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These data indicate favorable efficacy of tirabrutinib in patients with relapsed\/refractory PCNSL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>JapicCTI-173646.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noaa145","type":"journal-article","created":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T07:10:00Z","timestamp":1592291400000},"page":"122-133","source":"Crossref","is-referenced-by-count":184,"title":["Phase I\/II study of tirabrutinib, a second-generation Bruton\u2019s tyrosine kinase inhibitor, in relapsed\/refractory primary central nervous system lymphoma"],"prefix":"10.1093","volume":"23","author":[{"given":"Yoshitaka","family":"Narita","sequence":"first","affiliation":[{"name":"Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0018-1652","authenticated-orcid":false,"given":"Motoo","family":"Nagane","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Kyorin University Faculty of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Mishima","sequence":"additional","affiliation":[{"name":"Department of Neuro-Oncology\/Neurosurgery, Saitama Medical University International Medical Center, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhito","family":"Terui","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Cancer Institute Hospital, Japanese 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