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Here, we conducted a multicenter, phase II study of tirabrutinib in patients with treatment\u2010na\u00efve (Cohort A) or with relapsed\/refractory (Cohort B) Waldenstr\u00f6m\u2019s macroglobulinemia (WM). Patients were treated with tirabrutinib 480\u00a0mg once daily. The primary endpoint was major response rate (MRR; \u2265 partial response). Secondary endpoints included overall response rate (ORR; \u2265 minor response), time to major response (TTMR), progression\u2010free survival (PFS), overall survival (OS), and safety. In total, 27 patients (18 in Cohort A; 9 in Cohort B) were enrolled. The median age was 71\u00a0y, and the median serum immunoglobulin M level was 3600\u00a0mg\/dL. Among the patients, 96.2% had the <jats:italic>MYD88<jats:sup>L265P<\/jats:sup><\/jats:italic> mutation. MRR and ORR were 88.9% and 96.3%, respectively (Cohort A: MRR, 88.9%; ORR, 94.4%; Cohort B: MRR, 88.9%; ORR, 100%). Median TTMR was 1.87\u00a0mo. PFS and OS were not reached with a median follow\u2010up of 6.5 and 8.3\u00a0mo for Cohorts A and B, respectively. The most common adverse events (AEs) were rash (44.4%), neutropenia (25.9%), and leukopenia (22.2%), with most AEs classified as grade 1 or 2. Grade\u00a0\u2265\u00a03 AEs included neutropenia (11.1%), lymphopenia (11.1%), and leukopenia (7.4%). No grade 5 AEs were noted. All bleeding events were grade 1; none were associated with drug\u2010related atrial fibrillation or hypertension. Although the follow\u2010up duration was relatively short, the study met the primary endpoint. Therefore, tirabrutinib monotherapy is considered to be highly effective for both untreated and relapsed\/refractory WM with a manageable safety profile. (JapicCTI\u2010173646).<\/jats:p>","DOI":"10.1111\/cas.14561","type":"journal-article","created":{"date-parts":[[2020,7,8]],"date-time":"2020-07-08T13:35:23Z","timestamp":1594215323000},"page":"3327-3337","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["A multicenter, open\u2010label, phase II study of tirabrutinib (ONO\/GS\u20104059) in patients with Waldenstr\u00f6m\u2019s macroglobulinemia"],"prefix":"10.1111","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9860-8257","authenticated-orcid":false,"given":"Naohiro","family":"Sekiguchi","sequence":"first","affiliation":[{"name":"Department of Hematology National Hospital Organization Disaster Medical Center Tachikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Rai","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology Faculty of Medicine Kindai University Osakasayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Munakata","sequence":"additional","affiliation":[{"name":"Department of Hematology National Cancer Center Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenshi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Hematology Japanese Red Cross Medical Center Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Handa","sequence":"additional","affiliation":[{"name":"Department of Hematology Gunma University Graduate School of Medicine Maebashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirohiko","family":"Shibayama","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Osaka University Graduate School of Medicine Suita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Endo","sequence":"additional","affiliation":[{"name":"Department of Hematology Hokkaido University Hospital Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhito","family":"Terui","sequence":"additional","affiliation":[{"name":"Department of Hematology Oncology The Cancer Institute Hospital Japanese Foundation for Cancer Research Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Iwaki","sequence":"additional","affiliation":[{"name":"Department of Hematology Kanazawa University Hospital Kanazawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Fukuhara","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology Tohoku University Graduate School of Medicine Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiro","family":"Tatetsu","sequence":"additional","affiliation":[{"name":"Department of Hematology Kumamoto University Hospital Kumamoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4951-960X","authenticated-orcid":false,"given":"Shinsuke","family":"Iida","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology Nagoya City University Graduate School of Medical Sciences Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Hematology Kobe City Medical Center General Hospital Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryota","family":"Shiibashi","sequence":"additional","affiliation":[{"name":"Department of Clinical Development Ono Pharmaceutical Co., LTD. 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