{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:59:14Z","timestamp":1793386754859,"version":"4.5.0"},"reference-count":16,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"7","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:p>\n            <jats:italic>Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in<\/jats:italic>\n            JCO\n            <jats:italic>or elsewhere, for which the primary end point has already been reported.<\/jats:italic>\n          <\/jats:p>\n          <jats:p>\n            SEQUOIA (ClinicalTrials.gov identifier:\n            <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT03336333\">NCT03336333<\/jats:ext-link>\n            ) is a phase III, randomized, open-label trial that compared the oral Bruton tyrosine kinase inhibitor zanubrutinib to bendamustine plus rituximab (BR) in treatment-na\u00efve patients with chronic lymphocytic leukemia\/small lymphocytic lymphoma (CLL\/SLL). The initial prespecified analysis (median follow-up, 26.2 months) and subsequent analysis (43.7 months) found superior progression-free survival (PFS; the primary end point) in patients who received zanubrutinib compared with BR. At a median follow-up of 61.2 months, median PFS was not reached in zanubrutinib-treated patients; median PFS was 44.1 months in BR-treated patients (hazard ratio [HR], 0.29; one-sided\n            <jats:italic>P<\/jats:italic>\n            = .0001). Prolonged PFS was seen with zanubrutinib versus BR in patients with mutated immunoglobulin heavy-chain variable region (IGHV) genes (HR, 0.40; one-sided\n            <jats:italic>P<\/jats:italic>\n            = .0003) and unmutated IGHV genes (HR, 0.21 [95% CI, 0.14 to 0.33]; one-sided\n            <jats:italic>P<\/jats:italic>\n            &lt; .0001). Median overall survival (OS) was not reached in either treatment arm; estimated 60-month OS rates were 85.8% and 85.0% in zanubrutinib- and BR-treated patients, respectively. No new safety signals were detected. Adverse events were as expected with zanubrutinib; rate of atrial fibrillation was 7.1%. At a median follow-up of 61.2 months, the results supported the initial SEQUOIA findings and suggested that zanubrutinib was a favorable treatment option for untreated patients with CLL\/SLL.\n          <\/jats:p>","DOI":"10.1200\/jco-24-02265","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T02:10:14Z","timestamp":1733710214000},"page":"780-787","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":70,"title":["Zanubrutinib Versus Bendamustine and Rituximab in Patients With Treatment-Na\u00efve Chronic Lymphocytic Leukemia\/Small Lymphocytic Lymphoma: Median 5-Year Follow-Up of SEQUOIA"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct03336333","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3365-6562","authenticated-orcid":true,"given":"Mazyar","family":"Shadman","sequence":"first","affiliation":[{"name":"Fred Hutchinson Cancer Center, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talha","family":"Munir","sequence":"additional","affiliation":[{"name":"Haematology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3411-6357","authenticated-orcid":true,"given":"Tadeusz","family":"Robak","sequence":"additional","affiliation":[{"name":"Copernicus Memorial Hospital, Medical University of \u0141\u00f3d\u017a, \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2040-4961","authenticated-orcid":true,"given":"Jennifer R.","family":"Brown","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0459-6609","authenticated-orcid":true,"given":"Brad S.","family":"Kahl","sequence":"additional","affiliation":[{"name":"Siteman Cancer Center, Washington University School of Medicine, St Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3750-7342","authenticated-orcid":true,"given":"Paolo","family":"Ghia","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Vita-Salute San Raffaele, Milano, Italy"},{"name":"IRCCS Ospedale San Raffaele, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0135-4030","authenticated-orcid":true,"given":"Krzysztof","family":"Giannopoulos","sequence":"additional","affiliation":[{"name":"Experimental Hematooncology Department, Medical University of Lublin, Lublin, Poland"},{"name":"Hematology Department, St John's Cancer Centre, Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0331-5334","authenticated-orcid":true,"given":"Martin","family":"\u0160imkovi\u010d","sequence":"additional","affiliation":[{"name":"4th Department of Internal Medicine\u2014Haematology, Faculty of Medicine in Hradec Kr\u00e1lov\u00e9, University Hospital and Charles University in Prague, Hradec Kr\u00e1lov\u00e9, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"\u00d6sterborg","sequence":"additional","affiliation":[{"name":"Department of Hematology, Karolinska University Hospital Solna, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Laurenti","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia A.","family":"Walker","sequence":"additional","affiliation":[{"name":"Peninsula Health and Peninsula Private Hospital, Frankston, Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0308-6458","authenticated-orcid":true,"given":"Stephen S.","family":"Opat","sequence":"additional","affiliation":[{"name":"Lymphoma Research Group, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Ciepluch","sequence":"additional","affiliation":[{"name":"Department of Hematology, Copernicus Regional Oncology Centre, Gdansk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4462-3694","authenticated-orcid":true,"given":"Richard","family":"Greil","sequence":"additional","affiliation":[{"name":"Third Medical Department With Hematology, Medical Oncology, Rheumatology and Infectiology, Paracelsus Medical University, Salzburg, Austria"},{"name":"Salzburg Cancer Research Institute Center for Clinical Cancer and Immunology Trials, Salzburg, Austria"},{"name":"Cancer Cluster Salzburg, Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merit","family":"Hanna","sequence":"additional","affiliation":[{"name":"Department of Haematology, Waitemata District Health Board, Takapuna, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Tani","sequence":"additional","affiliation":[{"name":"Hematology Unit, Santa Maria delle Croci Hospital, Ravenna, 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