{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:29:42Z","timestamp":1787563782642,"version":"build-2736575974"},"reference-count":68,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,23]],"date-time":"2023-07-23T00:00:00Z","timestamp":1690070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Ibrutinib, the first-in-class Bruton\u2019s tyrosine kinase inhibitor (BTKi), is a commonly deployed therapeutic option for previously untreated and relapsed\/refractory (R\/R) patients with chronic lymphocytic leukemia (CLL). The use of ibrutinib is, however, partially limited by off-target side effects. Zanubrutinib (zanu) is a second-generation BTKi with enhanced target selectivity and occupancy of the kinase binding site. The SEQUOIA study showed that zanu significantly prolonged progression-free survival (PFS) when compared to bendamustine\u2013rituximab (BR) in treatment-naive CLL patients. More recently, data from the phase III ALPINE trial, which directly compared zanu with ibrutinib, demonstrated that zanu\u2019s advantages include an improved safety profile as well as enhanced clinical efficacy. Based on the results of the SEQUOIA and ALPINE pivotal trials, the Food and Drug Administration (FDA) and European Medicines Agency (EMA) licensed zanu for the treatment of patients with CLL or small lymphocytic lymphoma (SLL) in January 2023. The updated (v2.2023) National Comprehensive Cancer Network (NCCN) guidelines and the most recent German CLL algorithm suggest that zanu may replace first-generation BTKis as a preferred therapeutic option for patients with CLL\/SLL due to its increased selectivity for the kinase binding site, improved therapeutic efficacy, and favorable toxicity profile. Some drug class-related characteristics such as drug resistance, low complete remission (CR) rates, and indefinite treatment duration still remain with zanu, and the results from recently completed and ongoing fixed-duration clinical trials, combining zanu with an anti-BCL2 agent, are eagerly awaited with the possible promise of a reduced treatment duration and lower financial burden.<\/jats:p>","DOI":"10.3390\/cancers15143737","type":"journal-article","created":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T01:15:45Z","timestamp":1690161345000},"page":"3737","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Advancements in the Treatment of CLL: The Rise of Zanubrutinib as a Preferred Therapeutic Option"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2795-6507","authenticated-orcid":false,"given":"Stefano","family":"Molica","sequence":"first","affiliation":[{"name":"Queens Centre for Oncology and Haematology, Castle Hill Hospital, Hull University NHS Trust, Hull HU16 5JQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantine","family":"Tam","sequence":"additional","affiliation":[{"name":"Alfred Hospital, Melbourne, VIC 3004, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Allsup","sequence":"additional","affiliation":[{"name":"Queens Centre for Oncology and Haematology, Castle Hill Hospital, Hull University NHS Trust, Hull HU16 5JQ, UK"},{"name":"Centre of Biomedicine, Hull York Medical School, University of Hull, Hull HU16 5JQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Polliack","sequence":"additional","affiliation":[{"name":"Department of Hematology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1056\/NEJMoa1215637","article-title":"Targeting BTK with Ibrutinib in Relapsed Chronic Lymphocytic Leukemia","volume":"369","author":"Byrd","year":"2013","journal-title":"N. 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