Zanubrutinib led to significant improvements in progression-free survival (PFS) compared with bendamustine plus rituximab for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to phase III SEQUOIA trial results.
Constantine Tam, MD, of the Alfred Hospital, and colleagues, conducted the trial and published its results in The Lancet Oncology.
Investigators conducted the open-label, multicenter phase III trial at 153 centers across 14 countries and regions. The study included patients with untreated CLL or SLL who were aged 65 years or older or 18 years or older with comorbidities.
Patients without the del(17p13.1) abnormality were randomly assigned to receive zanubrutinib (n=241) or bendamustine-rituximab (n=238). A group of patients with del(17p13.1) received zanubrutinib (n=111) but their PFS outcomes were not analyzed or compared with the other treatment arms.
The median PFS was not reached in the zanubrutinib treatment arm (95% confidence interval [CI], not estimable [NE] to NE) nor in the bendamustine-rituximab treatment arm (95% CI, 28.1 months to NE) at a median follow-up of 26.2 months. PFS was significantly improved in the zanubrutinib treatment arm compared with the bendamustine-rituximab treatment arm (hazard ratio, 0.42; 95% CI, 0.28 to 0.63; two-sided P<.0001).
Researchers reported serious adverse events in 37% of patients in the zanubrutinib treatment arm, 50% of patients in the bendamustine-rituximab treatment arm and in 41% of patients with del(17p13.1) who received zanubrutinib. Neutropenia was the most common grade 3 or worse adverse event reported.
Adverse events causing death were reported in 5% of patients in the zanubrutinib treatment arm, 5% of patients in the bendamustine-rituximab treatment arm and 3% of patients with (17p13.1) who received zanubrutinib. COVID-19, diarrhea, and aspiration pneumonia were the most common causes of death.
“Zanubrutinib significantly improved progression-free survival versus bendamustine-rituximab, with an acceptable safety profile consistent with previous studies,” Dr. Tam and colleagues concluded. “These data support zanubrutinib as a potential new treatment option for untreated CLL and SLL.”
Tam CS, Brown JR, Kahl BS, et al. Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Lancet Oncol. 2022;23(8):1031-1043. doi:10.1016/S1470-2045(22)00293-5