{"entity":{"id":"paper-zanubrutinib-cll-lancet-oncol-2022","kind":"paper","name":"Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial","aka":[],"tldr":"Phase 2 or 3 results paper on Zanubrutinib in Chronic lymphocytic leukaemia, in The Lancet Oncology (2022), one of the most cited Europe PMC records with Zanubrutinib in its title.","summary":"Background: Zanubrutinib is a next-generation, selective Bruton tyrosine kinase inhibitor with efficacy in relapsed chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). We compared zanubrutinib with bendamustine-rituximab to determine its effectiveness as frontline therapy in patients with CLL or SLL.\n\nMethods: We conducted an open-label, multicentre, phase 3 study at 153 academic or community hospitals in 14 countries and regions. Eligible patients had untreated CLL or SLL requiring treatment as per International Workshop on CLL criteria; were aged 65 years or older, or 18 years or older and had comorbidities; and had an Eastern Cooperative Oncology Group performance status score of 0-2. A central interactive web response system randomly assigned patients without del(17)(p13·1) to zanubrutinib (group A) or bendamustine-rituximab (group B) by sequential block method (permutated blocks with a random block size of four). Patients with del(17)(p13·1) were enrolled in group C and received zanubrutinib. Zanubrutinib was administered orally at 160 mg twice per day (28-day cycles); bendamustine at 90 mg/m 2 of body surface area on days 1 and 2 for six cycles plus rituximab at 375 mg/m 2 of body surface area the day before or on day 1 of cycle 1, and 500 mg/m 2 of body surface area on day 1 of cycles 2-6, were administered intravenously. The primary endpoint was progression-free survival per independent review committee in the intention-to-treat population in groups A and B, with minimum two-sided α of 0·05 for superiority. Safety was analysed in all patients who received at least one dose of study treatment. The study is registered with ClinicalTrials.gov, NCT03336333, and is closed to recruitment.\n\nFindings: Between Oct 31, 2017, and July 22, 2019, 590 patients were enrolled; patients without del(17)(p13·1) were randomly assigned to zanubrutinib (group A; n=241) or bendamustine-rituximab (group B; n=238). At median follow-up of 26·2 months (IQR 23·7-29·6), median progression-free survival per independent review committee was not reached in either group (group A 95% CI not estimable [NE] to NE; group B 28·1 months to NE). Progression-free survival was significantly improved in group A versus group B (HR 0·42 [95% CI 0·28 to 0·63]; two-sided p<0·0001). The most common grade 3 or worse adverse event was neutropenia (27 [11%] of 240 patients in group A, 116 [51%] of 227 in group B, and 17 [15%] of 111 patients in group C). Serious adverse events occurred in 88 (37%) of 240 patients in group A, 113 (50%) of 227 patients in group B, and 45 (41%) of 111 patients in group C. Adverse events leading to death occurred in 11 (5%) of 240 patients in group A, 12 (5%) of 227 patients in group B, and three (3%) of 111 patients in group C, most commonly due to COVID-19 (four [2%] of 240 patients in group A), diarrhoea, and aspiration pneumonia (two each [1%] of 227 patients in group B).\n\nInterpretation: Zanubrutinib significantly improved progression-free survival versus bendamustine-rituximab, with an acceptable safety profile consistent with previous studies. These data support zanubrutinib as a potential new treatment option for untreated CLL and SLL.\n\nFunding: BeiGene.\n\nIndexed on Europe PMC as PubMed record 35810754 (DOI 10.1016/s1470-2045(22)00293-5). Its title names Zanubrutinib and its text names Chronic lymphocytic leukaemia; PubMed types it as a clinical trial report (Clinical Trial, Phase III, Research Support, Non-U.S. Gov't, Randomized Controlled Trial). It was matched automatically to the idea \"MRD-guided treatment duration in CLL\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Lancet Oncol 2022","url":"https://doi.org/10.1016/s1470-2045(22)00293-5"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/35810754/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/35810754"},{"label":"ClinicalTrials.gov NCT03336333","url":"https://clinicaltrials.gov/study/NCT03336333"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["sequoia"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2022,"doi":"10.1016/s1470-2045(22)00293-5","pmid":"35810754","authors":"Tam CS, Brown JR, Kahl BS, et al.","paperType":"rct","findings":[],"whatItMeans":"One of the most cited trial reports Europe PMC returns for Zanubrutinib in Chronic lymphocytic leukaemia, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by Zanubrutinib in the title and Chronic lymphocytic leukaemia in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper."]},"route":"/key-papers/paper-zanubrutinib-cll-lancet-oncol-2022/","neighbours":{"trial":[{"id":"sequoia","kind":"trial","name":"SEQUOIA","route":"/trials/sequoia/"}],"journal":[{"id":"lancet-oncology","kind":"journal","name":"The Lancet Oncology","route":"/journals/lancet-oncology/"}],"idea":[{"id":"idea-mrd-guided-stop-cll","kind":"idea","name":"MRD-guided treatment duration in CLL","route":"/ideas/idea-mrd-guided-stop-cll/"}]}}