{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:12:36Z","timestamp":1793142756328,"version":"4.5.0"},"reference-count":20,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"21","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,7,20]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>\n              Several chronic lymphocytic leukemia (CLL) studies have demonstrated promising efficacy with the combination of BCL2 and Bruton tyrosine kinase inhibitors; however, patients with CLL with del(17p) and\/or\n              <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n              mutation (\n              <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n              mut) comprised a small percentage of study populations or were excluded entirely. The purpose of the SEQUOIA Arm D cohort was to evaluate the combination of zanubrutinib + venetoclax in treatment-na\u00efve (TN) patients with CLL\/small lymphocytic lymphoma (SLL), in a large population of patients with\n              <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n              -aberrant disease.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>PATIENTS AND METHODS<\/jats:title>\n            <jats:p>Arm D is a nonrandomized cohort of patients aged 65 years and older (or 18-64 years with comorbidities). Patients received zanubrutinib from cycle 1 and venetoclax from cycle 4 (ramp-up) to cycle 28, followed by continuous zanubrutinib monotherapy until progressive disease (PD), unacceptable toxicity, or meeting undetectable minimal residual disease (uMRD)-guided stopping criteria.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              Between November 2019 and July 2022, 114 patients were enrolled: 66 (58%) with\n              <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n              -aberrant disease, 47 (41%) without\n              <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n              -aberrant disease, and 1 with missing\n              <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n              results. At a median follow-up of 31.2 months, 85 patients (75%) remained on zanubrutinib monotherapy; 29 patients (25%) discontinued zanubrutinib because of adverse event, uMRD-guided stopping criteria, PD, or other. In the intention-to-treat population, 59% of patients achieved peripheral blood uMRD. The 24-month progression-free survival estimate was 92% (95% CI, 85% to 96%). The most common any-grade treatment-emergent AEs (TEAEs) were COVID-19 (54%), diarrhea (41%), contusion (32%), and nausea (30%). The most common grade \u22653 TEAEs were neutropenia (17%), hypertension (10%), diarrhea (6%), and decreased neutrophil count (6%).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>\n              Zanubrutinib + venetoclax demonstrated impressive efficacy and a favorable safety profile in patients with TN CLL\/SLL, regardless of the presence of\n              <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n              -aberrant disease.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/jco-25-00758","type":"journal-article","created":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T08:00:23Z","timestamp":1748678423000},"page":"2409-2417","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":26,"title":["Zanubrutinib and Venetoclax for Patients With Treatment-Na\u00efve Chronic Lymphocytic Leukemia\/Small Lymphocytic Lymphoma With and Without Del(17p)\/\n            <i>TP53<\/i>\n            Mutation: SEQUOIA Arm D Results"],"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, Seattle, WA"},{"name":"University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2901-0769","authenticated-orcid":true,"given":"Talha","family":"Munir","sequence":"additional","affiliation":[{"name":"Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Ma","sequence":"additional","affiliation":[{"name":"Robert H. 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