{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T03:37:33Z","timestamp":1794281853425,"version":"4.9.0"},"reference-count":21,"publisher":"American Society of Hematology","issue":"26","license":[{"start":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T00:00:00Z","timestamp":1727136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,12,26]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>The ALPINE trial established the superiority of zanubrutinib over ibrutinib in patients with relapsed\/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma; here, we present data from the final comparative analysis with extended follow-up. Overall, 652 patients received zanubrutinib (n\u00a0=\u00a0327) or ibrutinib (n\u00a0=\u00a0325). At an overall median follow-up of 42.5 months, progression-free survival benefit with zanubrutinib vs ibrutinib was sustained (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.54-0.84), including in patients with del(17p)\/TP53 mutation (HR, 0.51; 95% CI, 0.33-0.78) and across multiple sensitivity analyses. Overall response rate remained higher with zanubrutinib compared with ibrutinib (85.6% vs 75.4%); responses deepened over time with complete response\/complete response with incomplete bone marrow recovery rates of 11.6% (zanubrutinib) and 7.7% (ibrutinib). Although median overall survival has not been reached in either treatment group, fewer zanubrutinib patients have died than ibrutinib patients (HR, 0.77 [95% CI, 0.55-1.06]). With median exposure time of 41.2 and 37.8 months in zanubrutinib and ibrutinib arms, respectively, the most common nonhematologic adverse events included COVID-19\u2013related infection (46.0% vs 33.3%), diarrhea (18.8% vs 25.6%), upper respiratory tract infection (29.3% vs 19.8%), and hypertension (27.2% vs 25.3%). Cardiac events were lower with zanubrutinib (25.9% vs 35.5%) despite similar rates of hypertension. Incidence of atrial fibrillation\/flutter was lower with zanubrutinib vs ibrutinib (7.1% vs 17.0%); no cardiac deaths were reported with zanubrutinib vs 6 cardiac deaths with ibrutinib. This analysis, at 42.5 months median follow-up, demonstrates that zanubrutinib remains more efficacious than ibrutinib with an improved overall safety\/tolerability profile. This trial was registered at www.ClinicalTrials.gov as #NCT03734016.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2024024667","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T13:57:53Z","timestamp":1727186273000},"page":"2706-2717","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":81,"title":["Sustained benefit of zanubrutinib vs ibrutinib in patients with R\/R CLL\/SLL: final comparative analysis of ALPINE"],"prefix":"10.1182","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2040-4961","authenticated-orcid":false,"given":"Jennifer R.","family":"Brown","sequence":"first","affiliation":[{"name":"1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Eichhorst","sequence":"additional","affiliation":[{"name":"2Department of Internal Medicine, University of Cologne, Center for Integrated Oncology Aachen, Bonn, Cologne, Duesseldorf, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Lamanna","sequence":"additional","affiliation":[{"name":"3Hematologic Malignancies Section, Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"4Division of Hematology\/Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, University of California, Irvine, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9759-5017","authenticated-orcid":false,"given":"Constantine S.","family":"Tam","sequence":"additional","affiliation":[{"name":"5Department of Haematology, The Alfred Hospital, Melbourne, VIC, Australia"},{"name":"6Department of Haematology, Monash University, Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7438-8277","authenticated-orcid":false,"given":"Lugui","family":"Qiu","sequence":"additional","affiliation":[{"name":"7Department of Lymphoma and Myeloma, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1879-8084","authenticated-orcid":false,"given":"Wojciech","family":"Jurczak","sequence":"additional","affiliation":[{"name":"8Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5467-1377","authenticated-orcid":false,"given":"Keshu","family":"Zhou","sequence":"additional","affiliation":[{"name":"9Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0331-5334","authenticated-orcid":false,"given":"Martin","family":"\u0160imkovi\u010d","sequence":"additional","affiliation":[{"name":"104th Department of Internal Medicine Haematology, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic"},{"name":"114th Department of Internal Medicine-Haematology, Faculty of Medicine in Hradec Kralove, Charles University, Hradec Kralove, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u0159\u00ed","family":"Mayer","sequence":"additional","affiliation":[{"name":"12Department of Internal Medicine-Hematology and Oncology, Masaryk University and University Hospital, Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Gillespie-Twardy","sequence":"additional","affiliation":[{"name":"13Medical Oncology and Hematology, Blue Ridge Cancer Care, Roanoke, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Ferrajoli","sequence":"additional","affiliation":[{"name":"14Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Ganly","sequence":"additional","affiliation":[{"name":"15Department of Haematology, Christchurch Hospital, Christchurch, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3645-7988","authenticated-orcid":false,"given":"Robert","family":"Weinkove","sequence":"additional","affiliation":[{"name":"16Te Rerenga Ora Blood and Cancer Centre, Te Whatu Ora Health New Zealand Capital Coast & Hutt Valley, Wellington, New Zealand"},{"name":"17Cancer Immunotherapy Programme, Malaghan Institute of Medical Research, Wellington, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Grosicki","sequence":"additional","affiliation":[{"name":"18Department of Hematology and Cancer Prevention, Health Sciences Faculty, Medical University of Silesia, Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Mital","sequence":"additional","affiliation":[{"name":"19Department of Hematology and Transplantology, Medical University of Gda\u0144sk, Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3411-6357","authenticated-orcid":false,"given":"Tadeusz","family":"Robak","sequence":"additional","affiliation":[{"name":"20Department of Hematology, Medical University of Lodz, Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Osterborg","sequence":"additional","affiliation":[{"name":"21Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden"},{"name":"22Department of Hematology, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Habte A.","family":"Yimer","sequence":"additional","affiliation":[{"name":"23Department of Hematology and Medical Oncology, Texas Oncology-Tyler\/US Oncology Research, Tyler, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Wang","sequence":"additional","affiliation":[{"name":"24Clinical 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