{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:56:18Z","timestamp":1789480578473,"version":"build-2803163510"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int J Hematol"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Zanubrutinib is a selective second-generation Bruton tyrosine kinase inhibitor approved in various B-cell malignancies globally. The phase 1\/2 BGB-3111-111 study evaluated the efficacy and safety of zanubrutinib 160 mg twice daily orally in Japanese patients with treatment-naive or relapsed\/refractory mature B-cell malignancies. Here, efficacy results from Part 2 in chronic lymphocytic leukemia\/small lymphocytic lymphoma (CLL\/SLL; n\u2009=\u200919) and Waldenstr\u00f6m macroglobulinemia (WM; n\u2009=\u200919), and safety results from Parts 1 (N\u2009=\u20096) and 2 (N\u2009=\u200949) are presented, with the first dose between 30 January, 2020, and 31 October, 2022. As of 10 May, 2023, investigator-assessed overall response rates were 100% (19\/19) and 94.7% (18\/19) in CLL\/SLL and WM, respectively, with median follow-up of 27.9 and 26.8 months; 24-month progression-free survival rates were 71.4% and 100% in treatment-naive and relapsed\/refractory CLL\/SLL and 83.9% and 100% in treatment-naive and relapsed\/refractory WM, respectively. In patients with B-cell malignancies, any-grade treatment-emergent adverse events (TEAEs) occurred in 53 (96.4%) and serious TEAEs in 18 (32.7%). Common TEAEs were platelet count decreased (18.2%), pyrexia (18.2%), COVID-19 (14.5%), and neutrophil count decreased (12.7%). With median follow-up &gt;\u20092 years, zanubrutinib demonstrated durable efficacy in Japanese patients with CLL\/SLL or WM and a favorable safety profile consistent with global phase 3 studies.<\/jats:p>","DOI":"10.1007\/s12185-025-03925-1","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T04:49:17Z","timestamp":1739767757000},"page":"483-493","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Zanubrutinib in Japanese treatment-naive and relapsed\/refractory patients with Waldenstr\u00f6m macroglobulinemia and CLL\/SLL"],"prefix":"10.1007","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9129-8057","authenticated-orcid":false,"given":"Koji","family":"Izutsu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Shimada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohmei","family":"Kubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuya","family":"Fujimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoaki","family":"Fujisaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shingo","family":"Kurahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Nagafuji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rika","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Jo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonori","family":"Nakazato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazutaka","family":"Sunami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senji","family":"Kasahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aileen","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohisa","family":"Takai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhua","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Takeuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,17]]},"reference":[{"key":"3925_CR1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.840616","volume":"12","author":"Y Ou","year":"2022","unstructured":"Ou Y, Long Y, Ji L, Zhan Y, Qiao T, Wang X, et al. Trends in disease burden of chronic lymphocytic leukemia at the global, regional, and national levels from 1990 to 2019, and projections until 2030: a population-based epidemiologic study. Front Oncol. 2022;12: 840616.","journal-title":"Front Oncol"},{"issue":"7","key":"3925_CR2","first-page":"493","volume":"46","author":"R Tomlinson","year":"2017","unstructured":"Tomlinson R. Chronic lymphocytic leukaemia: an updated approach to diagnosis and management in general practice. Aust Fam Physician. 2017;46(7):493\u20136.","journal-title":"Aust Fam Physician"},{"issue":"1","key":"3925_CR3","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1182\/hematology.2020000086","volume":"2020","author":"C Moreno","year":"2020","unstructured":"Moreno C. Standard treatment approaches for relapsed\/refractory chronic lymphocytic leukemia after frontline chemoimmunotherapy. Hematology. 2020;2020(1):33\u201340.","journal-title":"Hematology"},{"issue":"2","key":"3925_CR4","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1007\/s12272-019-01124-1","volume":"42","author":"H-O Kim","year":"2019","unstructured":"Kim H-O. Development of BTK inhibitors for the treatment of B-cell malignancies. Arch Pharmacal Res. 2019;42(2):171\u201381.","journal-title":"Arch Pharmacal Res"},{"issue":"2","key":"3925_CR5","doi-asserted-by":"publisher","first-page":"119","DOI":"10.3109\/08830185.2012.664797","volume":"31","author":"JJ Buggy","year":"2012","unstructured":"Buggy JJ, Elias L. Bruton tyrosine kinase (BTK) and its role in B-cell malignancy. Int Rev Immunol. 2012;31(2):119\u201332.","journal-title":"Int Rev Immunol"},{"issue":"1","key":"3925_CR6","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1200\/JCO.2012.44.4281","volume":"31","author":"A Wiestner","year":"2013","unstructured":"Wiestner A. Targeting B-cell receptor signaling for anticancer therapy: the Bruton\u2019s tyrosine kinase inhibitor ibrutinib induces impressive responses in B-cell malignancies. J Clin Oncol. 2013;31(1):128\u201330.","journal-title":"J Clin Oncol"},{"key":"3925_CR7","unstructured":"Imbruvica (ibrutinib). Prescribing information. Pharmacyclics LLC, Janssen; Japan; 2023."},{"issue":"17","key":"3925_CR8","doi-asserted-by":"publisher","first-page":"7923","DOI":"10.1021\/acs.jmedchem.9b00687","volume":"62","author":"Y Guo","year":"2019","unstructured":"Guo Y, Liu Y, Hu N, Yu D, Zhou C, Shi G, et al. Discovery of zanubrutinib (BGB-3111), a novel, potent, and selective covalent inhibitor of Bruton\u2019s tyrosine kinase. J Med Chem. 2019;62(17):7923\u201340.","journal-title":"J Med Chem"},{"issue":"8","key":"3925_CR9","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1016\/S1470-2045(22)00293-5","volume":"23","author":"CS Tam","year":"2022","unstructured":"Tam CS, Brown JR, Kahl BS, Ghia P, Giannopoulos K, Jurczak W, et al. Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Lancet Oncol. 2022;23(8):1031\u201343.","journal-title":"Lancet Oncol"},{"issue":"4","key":"3925_CR10","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1056\/NEJMoa2211582","volume":"388","author":"JR Brown","year":"2023","unstructured":"Brown JR, Eichhorst B, Hillmen P, Jurczak W, Ka\u017amierczak M, Lamanna N, et al. Zanubrutinib or ibrutinib in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2023;388(4):319\u201332.","journal-title":"N Engl J Med"},{"key":"3925_CR11","unstructured":"Dimopoulos MA, Opat S, D'Sa S, Jurczak W, Lee H-P, Cull G, et al. Zanubrutinib versus ibrutinib in symptomatic Waldenstr\u00f6m macroglobulinemia: final analysis from the randomized phase III ASPEN study. J Clin Oncol 2023:JCO. 22.02830."},{"key":"3925_CR12","unstructured":"Brukinsa (zanubrutinib) [package insert] San Mateo, CA, BeiGene USA; 2023."},{"key":"3925_CR13","unstructured":"Brukinsa (zanubrutinib). Summary of product characteristics. BeiGene Ireland, Ltd; 2023."},{"key":"3925_CR14","unstructured":"Brukinsa (zanubrutinib). Packaging insert. BeiGene, Co. 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Activity of Zanubrutinib (Zanu) in Japanese Patients with Waldenstr\u00f6m Macroglobulinemia. 85th Annual Meeting of the Japanese Society of Hematology; October 13-15, 2023; Tokyo, Japan. Abstract 30058"},{"issue":"5","key":"3925_CR22","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1200\/JCO.22.00510","volume":"41","author":"P Hillmen","year":"2023","unstructured":"Hillmen P, Eichhorst B, Brown JR, Lamanna N, O\u2019Brien SM, Tam CS, et al. Zanubrutinib versus ibrutinib in relapsed\/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma: interim analysis of a randomized phase III trial. J Clin Oncol. 2023;41(5):1035.","journal-title":"J Clin Oncol"},{"issue":"26","key":"3925_CR23","doi-asserted-by":"publisher","first-page":"2706","DOI":"10.1182\/blood.2024024667","volume":"144","author":"JR Brown","year":"2024","unstructured":"Brown JR, Eichhorst B, Lamanna N, O\u2019Brien SM, Tam CS, Qiu L, et al. Sustained benefit of zanubrutinib vs ibrutinib in patients with R\/R CLL\/SLL: final comparative analysis of ALPINE. Blood. 2024;144(26):2706\u20132717.","journal-title":"Blood"}],"container-title":["International Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-025-03925-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12185-025-03925-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12185-025-03925-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T13:17:52Z","timestamp":1742390272000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12185-025-03925-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,17]]},"references-count":23,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["3925"],"URL":"https:\/\/doi.org\/10.1007\/s12185-025-03925-1","relation":{},"ISSN":["0925-5710","1865-3774"],"issn-type":[{"value":"0925-5710","type":"print"},{"value":"1865-3774","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,17]]},"assertion":[{"value":"23 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 January 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 February 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Takayuki Ishikawa, Kazuyuki Shimada, Kohmei Kubo, Takeshi Kondo, Tomoaki Fujisaki, Shingo Kurahashi, Rika Sakai, Tatsuro Jo, Tomonori Nakazato, Masahiro Takeuchi: No conflict of interest to disclose. Koji Izutsu: Honoraria from Ono Pharmaceutical, Janssen; research funding from AstraZeneca, AbbVie, Incyte, Bristol Myers Squibb, Novartis, Janssen, Yakult, Daiichi Sankyo, Chugai, BeiGene, Genmab. Katsuya Fujimoto: Research funding from Parexel International Co, Ltd, Insight Biosciences Japan, LLC. Kazutaka Sunami: Honoraria from Celgene, Bristol Myers Squibb, Takeda Pharmaceutical, Sanofi; research funding from Ono Pharmaceutical, MSD, Celgene, AbbVie G.K., Takeda Pharmaceutical, Sanofi, Bristol Myers Squibb, Daiichi Sankyo, Alexion Pharma, GSK, Otsuka Pharmaceutical, Novartis Pharma, Astellas, Amgen, Janssen Pharma, Chugai Pharmaceutical, Kyowa Kirin, Pfizer. Senji Kasahara: Honoraria from Daiichi Sankyo; research funding from Novartis Pharma, Astellas Pharma, Daiichi Sankyo. Aileen Cohen: Consultant and equity holder with BeiGene. Motohisa Takai, Jinhua Zhong: Employment and stock options from BeiGene. Koji Nagafuji: An editor of International Journal of Hematology during the review process.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}