Among patients with treatment-naïve chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), zanubrutinib appears to improve progression-free survival (PFS), but not the complete response rate or overall survival rate, compared with bendamustine plus rituximab (BR), according to research presented at the 2021 American Society of Hematology (ASH) Annual Meeting.
Previous study has suggested that zanubrutinib, a next-generation inhibitor of the Bruton tyrosine kinase, may be safe and active among patients with CLL/SLL. For the randomized phase 3 SEQUOIA trial (ClinicalTrials.gov Identifier: NCT03336333), researchers are investigating the comparative safety and efficacy of zanubrutinib and BR in a treatment-naïve patient group. At the meeting, researchers presented the interim results from SEQUOIA cohort 1.
All patients enrolled to SEQUOIA, for which recruitment is ongoing, are treatment-naïve and have CLL/SLL without 17p deletion. Between 2017 and 2019, 479 patients were randomly assigned to receive zanubrutinib (241 patients) or BR (238 patients). In the zanubrutinib and BR groups, the median age was 70 years, 53.4% vs 52.4% of patients had unmutated IGHV, respectively, and 17.8% vs 19.3% of patients had 11q deletion.
The median follow-up was 26.2 months. Independent review committee–assessed PFS suggested improvement with zanubrutinib (hazard ratio, 0.42; 95% CI: 0.28-0.63; P <.0001). Investigator assessed–PFS showed similar improvement, and the improvement was noted regardless of age and 11q deletion status, though patients with mutated IGHV did not see a PFS benefit (P =.0929).
In the zanubrutinib and BR groups, the overall response rates were 94.6% and 85.3%, respectively; the complete response rates were, however, 6.6% vs 15.1%. The estimated 2-year overall survival rate was 94.3% with zanubrutinib vs 94.6% with BR.
The safety analysis showed that grade 3 or worse adverse events occurred in 52.5% of patients who received zanubrutinib vs 74.4% of patients who received BR. In the zanubrutinib vs BR groups, the most common grade 3 or worse events were neutropenia (9.2%) and hypertension (6.3%) vs neutropenia (41.4%) and decreased neutrophil count (10.6%), respectively.
Adverse events that led to patient death were noted in 4.6% of those in the zanubrutinib group vs 5.3% of those in the BR group.
Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Tam CS, Giannopoulos K, Jurczak W, et al. SEQUOIA: results of a phase 3 randomized study of zanubrutinib versus bendamustine + rituximab (BR) in patients with treatment-naïve (TN) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Presented at ASH 2021; December 11-14, 2021. Abstract 396.
This article originally appeared on Hematology Advisor