# Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial

Source: https://onco.cc/key-papers/paper-zanubrutinib-cll-lancet-oncol-2022/  
OnCo record `paper-zanubrutinib-cll-lancet-oncol-2022` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

Methods: 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.

Findings: 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).

Interpretation: 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.

Funding: BeiGene.

Indexed 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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: The Lancet Oncology
- Year: 2022
- DOI: 10.1016/s1470-2045(22)00293-5
- Authors: Tam CS, Brown JR, Kahl BS, et al.
- What it means: 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.

## Sources

- Lancet Oncol 2022: https://doi.org/10.1016/s1470-2045(22)00293-5
- PubMed: https://pubmed.ncbi.nlm.nih.gov/35810754/
- Europe PMC: https://europepmc.org/article/MED/35810754
- ClinicalTrials.gov NCT03336333: https://clinicaltrials.gov/study/NCT03336333

## Connected records

- trials: [SEQUOIA](https://onco.cc/trials/sequoia/)
- journals: [The Lancet Oncology](https://onco.cc/journals/lancet-oncology/)
- ideas: [MRD-guided treatment duration in CLL](https://onco.cc/ideas/idea-mrd-guided-stop-cll/)

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