{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T01:08:21Z","timestamp":1793236101401,"version":"4.5.0"},"reference-count":31,"publisher":"American Society of Hematology","issue":"12","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,6,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Zanubrutinib, a highly selective Bruton tyrosine kinase inhibitor, was evaluated in a phase 1\/2 study in patients with various B-cell malignancies. In the subgroup of patients with relapsed\/refractory (R\/R) mantle cell lymphoma (MCL), zanubrutinib was administered as 160 mg twice daily (n = 14), 320 mg once daily (n = 18), or \u2264160 mg total dose (n = 5). Herein, we report results for patients receiving a total daily dose of 320 mg (N = 32). Median study follow-up was 18.8 months. Eighteen patients discontinued treatment, 10 because of progressive disease and 8 because of adverse events (AEs); 1 AE (peripheral edema) was considered to be related to zanubrutinib treatment. The most common AEs were diarrhea (43.8%), contusion (37.5%), constipation (31.3%), and upper respiratory tract infection (31.3%). Infection was the most commonly reported AE of interest (18.8% of patients experienced grade \u22653 infection). At least 1 AE of grade \u22653 was reported in 59.4% of patients; grade \u22653 AEs that were reported in &amp;gt;2 patients were anemia (12.5%), pneumonia (9.4%), and myalgia (9.4%). Overall response rate was 84%, with 25% achieving a complete response. Median duration of response was 18.5 months. Median progression-free survival (PFS) was 21.1 months. Zanubrutinib was well tolerated and demonstrated activity in patients with R\/R MCL. The trial is registered at www.clinicaltrials.gov as #NCT02343120.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020004074","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T11:35:31Z","timestamp":1624275331000},"page":"2577-2585","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":103,"title":["Zanubrutinib for the treatment of relapsed or refractory mantle cell lymphoma"],"prefix":"10.1182","volume":"5","author":[{"given":"Constantine S.","family":"Tam","sequence":"first","affiliation":[{"name":"Peter MacCallum Cancer Centre, Melbourne, VIC, Australia;"},{"name":"St Vincent\u2019s Hospital, Fitzroy, VIC, Australia;"},{"name":"Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia;"},{"name":"Royal Melbourne Hospital, Parkville, VIC, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Opat","sequence":"additional","affiliation":[{"name":"Monash Health, Clayton, VIC, Australia;"},{"name":"Department of Haematology, Monash University, Clayton, VIC, 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":"Gavin","family":"Cull","sequence":"additional","affiliation":[{"name":"Sir Charles Gairdner Hospital, Perth, WA, Australia;"},{"name":"Pathology and Laboratory Medicine, 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":"Tycel J.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Michigan, Ann Arbor, MI;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Seog","family":"Kim","sequence":"additional","affiliation":[{"name":"Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Rule","sequence":"additional","affiliation":[{"name":"Peninsula Medical School, University of Plymouth, Plymouth, United Kingdom;"}],"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":"Rachel","family":"Wei","sequence":"additional","affiliation":[{"name":"BeiGene USA, Inc., San Mateo, CA;"}],"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":"Jane","family":"Huang","sequence":"additional","affiliation":[{"name":"BeiGene USA, Inc., San Mateo, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9748-5486","authenticated-orcid":false,"given":"Michael","family":"Wang","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center, Houston, TX; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8009-4593","authenticated-orcid":false,"given":"Judith","family":"Trotman","sequence":"additional","affiliation":[{"name":"Concord Repatriation Hospital, The University of Sydney, Sydney, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2021,6,21]]},"reference":[{"key":"2021062115315629100_B1","doi-asserted-by":"crossref","first-page":"103038","DOI":"10.1016\/j.critrevonc.2020.103038","article-title":"Mantle cell lymphoma","volume":"153","author":"Cortelazzo","year":"2020","journal-title":"Crit Rev Oncol Hematol."},{"issue":"2","key":"2021062115315629100_B2","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/bjh.15170","article-title":"Impact of novel therapies for mantle cell lymphoma in the real world setting: a report from the UK\u2019s Haematological Malignancy Research Network (HMRN)","volume":"181","author":"Smith","year":"2018","journal-title":"Br J Haematol."},{"issue":"8","key":"2021062115315629100_B3","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1080\/10428194.2019.1571205","article-title":"Recent advances and future directions in mantle cell lymphoma research: report of the 2018 mantle cell lymphoma consortium workshop","volume":"60","author":"Kahl","year":"2019","journal-title":"Leuk Lymphoma."},{"issue":"16","key":"2021062115315629100_B4","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1182\/blood-2018-03-791392","article-title":"Update on mantle cell lymphoma","volume":"132","author":"Maddocks","year":"2018","journal-title":"Blood."},{"issue":"4","key":"2021062115315629100_B5","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1200\/JCO.1996.14.4.1269","article-title":"Mantle-cell lymphoma: a population-based clinical study","volume":"14","author":"Velders","year":"1996","journal-title":"J Clin Oncol."},{"issue":"6","key":"2021062115315629100_B6","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41408-019-0209-5","article-title":"Patterns of survival in patients with recurrent mantle cell lymphoma in the modern era: progressive shortening in response duration and survival after each relapse","volume":"9","author":"Kumar","year":"2019","journal-title":"Blood Cancer J."},{"issue":"4","key":"2021062115315629100_B7","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1111\/ejh.12442","article-title":"Role of allogeneic stem cell transplantation in mantle cell lymphoma","volume":"94","author":"Cohen","year":"2015","journal-title":"Eur J Haematol."},{"issue":"14","key":"2021062115315629100_B8","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1056\/NEJMoa1914347","article-title":"KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma","volume":"382","author":"Wang","year":"2020","journal-title":"N Engl J Med."},{"issue":"10","key":"2021062115315629100_B9","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/j.leukres.2013.07.028","article-title":"Bruton tyrosine kinase is commonly overexpressed in mantle cell lymphoma and its attenuation by Ibrutinib induces apoptosis","volume":"37","author":"Cinar","year":"2013","journal-title":"Leuk Res."},{"issue":"1","key":"2021062115315629100_B10","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1182\/asheducation-2013.1.553","article-title":"Targeting B-cell receptor signaling: changing the paradigm","volume":"2013","author":"Fowler","year":"2013","journal-title":"Hematology (Am Soc Hematol Educ Program)."},{"key":"2021062115315629100_B11","year":"2020"},{"key":"2021062115315629100_B12","year":"2019"},{"key":"2021062115315629100_B13","year":"2019"},{"issue":"5","key":"2021062115315629100_B14","doi-asserted-by":"crossref","first-page":"e211","DOI":"10.3324\/haematol.2018.205229","article-title":"Ibrutinib for the treatment of relapsed\/refractory mantle cell lymphoma: extended 3.5-year follow up from a pooled analysis","volume":"104","author":"Rule","year":"2019","journal-title":"Haematologica."},{"issue":"10121","key":"2021062115315629100_B15","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S0140-6736(17)33108-2","article-title":"Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial","volume":"391","author":"Wang","year":"2018","journal-title":"Lancet."},{"issue":"11","key":"2021062115315629100_B16","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1182\/blood.2019001160","article-title":"Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL","volume":"134","author":"Tam","year":"2019","journal-title":"Blood."},{"issue":"1","key":"2021062115315629100_B17","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1200\/JCO.2012.42.7906","article-title":"Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed\/refractory B-cell malignancies","volume":"31","author":"Advani","year":"2013","journal-title":"J Clin Oncol."},{"issue":"23","key":"2021062115315629100_B18","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1182\/blood.V126.23.832.832","article-title":"The BTK inhibitor, Bgb-3111, is safe, tolerable, and highly active in patients with relapsed\/refractory B-cell malignancies: initial report of a phase 1 first-in-human trial","volume":"126","author":"Tam","year":"2015","journal-title":"Blood."},{"issue":"22","key":"2021062115315629100_B19","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.2217\/fon-2018-0163","article-title":"A head-to-head phase III study comparing zanubrutinib versus ibrutinib in patients with Waldenstr\u00f6m macroglobulinemia","volume":"14","author":"Tam","year":"2018","journal-title":"Future Oncol."},{"issue":"22","key":"2021062115315629100_B20","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1182\/blood.V128.22.642.642","article-title":"Twice daily dosing with the highly specific BTK inhibitor, Bgb-3111, achieves complete and continuous BTK occupancy in lymph nodes, and is associated with durable responses in patients (pts) with chronic lymphocytic leukemia (CLL)\/small lymphocytic lymphoma (SLL)","volume":"128","author":"Tam","year":"2016","journal-title":"Blood."},{"key":"2021062115315629100_B21","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1097\/01.HS9.0000562920.26603.5b","article-title":"Pooled analysis of safety data from monotherapy studies of the Bruton tyrosine kinase (BTK) inhibitor, zanubrutinib (BGB-3111) in B-cell malignancies","volume":"3","author":"Tam","year":"2019","journal-title":"HemaSphere."},{"key":"2021062115315629100_B22","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1002\/hon.2437_58","article-title":"Bruton\u2019s tyrosine kinase (BTK) inhibitor BGB-3111 demonstrates high very good partial response (VGPR) rate in patients with Waldenstr\u00f6m macroglobulinemia (WM)","volume":"35","author":"Trotman","year":"2017","journal-title":"Hematol Oncol."},{"issue":"27","key":"2021062115315629100_B23","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1200\/JCO.2013.54.8800","article-title":"Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification","volume":"32","author":"Cheson","year":"2014","journal-title":"J Clin Oncol."},{"issue":"4","key":"2021062115315629100_B24","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1093\/biomet\/26.4.404","article-title":"The use of confidence or fiducial limits illustrated in the case of the binomial","volume":"26","author":"Clopper","year":"1934","journal-title":"Biometrika."},{"issue":"1","key":"2021062115315629100_B25","doi-asserted-by":"crossref","first-page":"29","DOI":"10.2307\/2530286","article-title":"A confidence interval for the median survival time","volume":"38","author":"Brookmeyer","year":"1982","journal-title":"Biometrics."},{"issue":"3","key":"2021062115315629100_B26","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1093\/annonc\/mdn656","article-title":"Bortezomib in patients with relapsed or refractory mantle cell lymphoma: updated time-to-event analyses of the multicenter phase 2 PINNACLE study","volume":"20","author":"Goy","year":"2009","journal-title":"Ann Oncol."},{"issue":"3","key":"2021062115315629100_B27","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S1470-2045(15)00559-8","article-title":"Lenalidomide versus investigator\u2019s choice in relapsed or refractory mantle cell lymphoma (MCL-002; SPRINT): a phase 2, randomised, multicentre trial","volume":"17","author":"Trn\u011bn\u00fd","year":"2016","journal-title":"Lancet Oncol."},{"issue":"12","key":"2021062115315629100_B28","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1111\/imj.13261","article-title":"Incidence of cutaneous squamous cell carcinoma in a New Zealand population of chronic lymphocytic leukaemia patients","volume":"46","author":"Hock","year":"2016","journal-title":"Intern Med J."},{"issue":"7","key":"2021062115315629100_B29","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1038\/bjc.2011.313","article-title":"Second cancer incidence and cancer mortality among chronic lymphocytic leukaemia patients: a population-based study","volume":"105","author":"Royle","year":"2011","journal-title":"Br J Cancer."},{"key":"2021062115315629100_B30","doi-asserted-by":"crossref","first-page":"8007","DOI":"10.1200\/JCO.2020.38.15_suppl.8007","article-title":"ASPEN: Results of a phase III randomized trial of zanubrutinib versus ibrutinib for patients with Waldenstr\u00f6m macroglobulinemia (WM)","volume":"38","author":"Tam","year":"2020","journal-title":"J Clin Oncol."},{"key":"2021062115315629100_B31","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1182\/blood-2018-99-117956","article-title":"Safety and activity of the investigational Bruton tyrosine kinase inhibitor zanubrutinib (BGB-3111) in patients with mantle cell lymphoma from a phase 2 trial","volume":"132","year":"2018","journal-title":"Blood."}],"container-title":["Blood Advances"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/5\/12\/2577\/1810345\/advancesadv2020004074.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/5\/12\/2577\/1810345\/advancesadv2020004074.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T11:35:54Z","timestamp":1624275354000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/bloodadvances\/article\/5\/12\/2577\/476187\/Zanubrutinib-for-the-treatment-of-relapsed-or"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,21]]},"references-count":31,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2021,6,22]]}},"URL":"https:\/\/doi.org\/10.1182\/bloodadvances.2020004074","relation":{},"ISSN":["2473-9529","2473-9537"],"issn-type":[{"value":"2473-9529","type":"print"},{"value":"2473-9537","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,21]]}}}