{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:51:45Z","timestamp":1790754705503,"version":"4.1.0"},"reference-count":29,"publisher":"American Society of Hematology","issue":"18","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,10,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Inhibitors of Bruton\u2019s tyrosine kinase (BTK) have established therapeutic activity in patients with Waldenstr\u00f6m macroglobulinemia (WM). Zanubrutinib, a potent and selective BTK inhibitor, was evaluated in a phase 1\/2 study in patients with WM who were either treatment-na\u00efve (TN) or had relapsed\/refractory (R\/R) disease. Patients had disease requiring treatment per International Workshop on Waldenstr\u00f6m Macroglobulinemia (IWWM) criteria. Treatment was 160 mg of oral zanubrutinib twice daily (n = 50) or 320 mg once daily (n = 23). Efficacy endpoints included overall response rate (ORR) and very good partial response\/complete response (VGPR\/CR) rates per IWWM-6 criteria (with modification of VGPR definition published previously). Between September 2014 and March 2018, 77 patients (24 TN and 53 R\/R) began treatment. At a median follow-up of 36.0 months for patients with R\/R disease and 23.5 months for TN, 72.7% remained on treatment. Reasons for treatment discontinuation included any adverse events in 13.0% of patients (1 treatment related), disease progression (10.4%), and other (3.9%). The ORR was 95.9%, and the VGPR\/CR rate was 45.2%, which increased over time: 20.5% at 6 months, 32.9% at 12 months, and 43.8% at 24 months. Estimated 3-year progression-free survival rate was 80.5%, and overall survival rate was 84.8%. Adverse events of interest included contusion (32.5%, all grade 1), neutropenia (18.2%), major hemorrhage (3.9%), atrial fibrillation\/flutter (5.2%), and grade 3 diarrhea (2.6%). Long-term treatment with single-agent zanubrutinib resulted in deep and durable responses in some patients with WM. The safety profile of long-term zanubrutinib therapy in these patients was acceptable. This trial was registered at www.clinicaltrials.gov as #NCT02343120.<\/jats:p>","DOI":"10.1182\/blood.2020006449","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T21:06:11Z","timestamp":1595451971000},"page":"2027-2037","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":107,"title":["Zanubrutinib for the treatment of patients with Waldenstr\u00f6m macroglobulinemia: 3 years of follow-up"],"prefix":"10.1182","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8009-4593","authenticated-orcid":false,"given":"Judith","family":"Trotman","sequence":"first","affiliation":[{"name":"Department of Haematology, Concord Repatriation General Hospital and Faculty of Medicine and Health, University of Sydney, Concord, NSW, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Opat","sequence":"additional","affiliation":[{"name":"Clinical Haematology Unit, Monash Health and Monash University, Clayton, VIC, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Gottlieb","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health, University of Sydney, Westmead Hospital Sydney, Sydney, NSW, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Simpson","sequence":"additional","affiliation":[{"name":"North Shore Hospital, Auckland, New Zealand;"},{"name":"BeiGene USA, Inc., San Mateo, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Marlton","sequence":"additional","affiliation":[{"name":"Department of Haematology, Princess Alexandra Hospital, Woolloongabba, Brisbane, QLD, Australia;"},{"name":"University of Queensland Faculty of Medicine, Brisbane, QLD, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Cull","sequence":"additional","affiliation":[{"name":"Haematology Department, Sir Charles Gairdner Hospital, Nedlands, WA, Australia;"},{"name":"Department of Lymphoma\/Myeloma, University of Western Australia, Perth, WA, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Munoz","sequence":"additional","affiliation":[{"name":"Banner MD Anderson Cancer Center, Gilbert, AZ;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Tedeschi","sequence":"additional","affiliation":[{"name":"ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7341-5720","authenticated-orcid":false,"given":"Andrew W.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Haematology Department, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2188-6835","authenticated-orcid":false,"given":"John F.","family":"Seymour","sequence":"additional","affiliation":[{"name":"Haematology Department, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC, Australia;"},{"name":"Department of Medicine, University of Melbourne, Melbourne, VIC, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siminder Kaur","family":"Atwal","sequence":"additional","affiliation":[{"name":"BeiGene USA, Inc., San Mateo, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiling","family":"Yu","sequence":"additional","affiliation":[{"name":"BeiGene (Shanghai) Co., Ltd., Shanghai, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Novotny","sequence":"additional","affiliation":[{"name":"BeiGene USA, Inc., San Mateo, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Holmgren","sequence":"additional","affiliation":[{"name":"BeiGene USA, Inc., San Mateo, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwen","family":"Tan","sequence":"additional","affiliation":[{"name":"BeiGene (Shanghai) Co., Ltd., Shanghai, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Hilger","sequence":"additional","affiliation":[{"name":"BeiGene USA, Inc., San Mateo, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Huang","sequence":"additional","affiliation":[{"name":"BeiGene USA, Inc., San Mateo, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantine S.","family":"Tam","sequence":"additional","affiliation":[{"name":"Haematology Department, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC, Australia;"},{"name":"Department of Medicine, 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