Zanubrutinib improves progression-free survival (PFS), when compared with bendamustine plus rituximab, in patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to results of the phase 3 SEQUOIA study.
Based on these results, researchers concluded that zanubrutinib may be a potential new treatment option for this patient population. The researchers reported the study findings in The Lancet Oncology.
The SEQUOIA trial (ClinicalTrials.gov Identifier: NCT03336333) enrolled patients with previously untreated CLL/SLL. Patients without del(17p13.1) were randomly assigned to receive zanubrutinib alone (n=241) or bendamustine plus rituximab (n=238).
At a median follow-up of 26.2 months, the median PFS was not reached in either treatment arm. However, PFS was superior in patients assigned to zanubrutinib (hazard ratio [HR], 0.42; 95% CI, 0.28-0.63; P <.0001).
At 24 months, the PFS rate was 85.5% in the zanubrutinib arm and 69.5% in the bendamustine-rituximab arm. PFS was superior in the zanubrutinib arm regardless of patient age, sex, or high-risk disease status.
The overall response rate was 94.6% in the zanubrutinib arm and 85.3% in the bendamustine-rituximab arm. The median duration of response was not reached and 30.6 months, respectively.
The median overall survival (OS) was not reached in either treatment arm. The 24-month OS rate was 94.3% in the zanubrutinib arm and 94.6% in the bendamustine-rituximab arm (HR, 1.07; 95% CI, 0.51-2.22; P =.87).
The researchers also analyzed a third group of 111 patients who had del(17p13.1). All of these patients received zanubrutinib. In this group, the 24-month PFS rate was 88.9%, and the 24-month OS rate was 93.6%. The overall response rate was 90.0%, and the median duration of response was not reached.
Serious adverse events (AEs) occurred in 37% of patients randomly assigned to zanubrutinib, 50% of patients assigned to bendamustine-rituximab, and 41% of patients with del(17p13.1) who received zanubrutinib.
Fatal AEs occurred in 5% of patients in each of the randomized arms. Common causes of death were COVID-19 or cardiovascular AEs in the zanubrutinib arm and diarrhea or aspiration pneumonia in the bendamustine-rituximab arm.
“Zanubrutinib significantly improved progression-free survival versus bendamustine–rituximab, with an acceptable safety profile consistent with previous studies,” the researchers concluded. “These data support zanubrutinib as a potential new treatment option for untreated CLL and SLL.”
Disclosures: This research was supported by BeiGene. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Tam CS, Brown JR, Kahl BS, et al. Zanubrutinib versus bendamustine and rituximab in untreated chronic lympocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): A randomized, controlled, phase 3 trial. Lancet Oncol. Published online July 7, 2022. doi:10.1016/S1470-2045(22)00293-5