Researchers have reported the clinical efficacy and safety of the Bruton tyrosine kinase (BTK) zanubrutinib for treatment-naïve chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). The findings were recently published in the journal Clinical lymphoma myeloma and leukaemia.
Zanubrutinib is a new frontline treatment for naïve CLL/SLL, and its safety and efficiency were examined in the phase III SEQUOIA study. SEQUOIA is a global, open-label, randomised phase III study that enrolled 479 (median age, 70 years) treatment-naïve CLL/SLL patients without 17p deletion. The participants were randomly (1:1) assigned to receive either zanubrutinib (n=241) or bendamustine + rituximab (BR, n=238). The study’s primary endpoint was progression-free survival (PFS, assessed by an independent review committee or IRC), and the secondary endpoints included investigator-assessed (INV) PFS, overall response rate (ORR), overall survival (OS), and safety.
At a median follow-up of 26.2 months, zanubrutinib significantly improved the PFS by both IRC (HR 0.42; 2-sided p<0.0001) and INV (HR 0.42; 2-sided p=0.0001). The clinical benefits were observed across age, Binet stage, 11q status, bulky disease and unmutated IGHV (HR 0.24; 2-sided p<0.0001). The improvement with zanubrutinib versus BR was seen in 24-month PFS-IRC (85.5% vs 69.5%), ORR-IRC (94.6% vs 85.3%), complete response rate (6.6% vs 15.1%), ORR-INV (97.5% vs 88.7%), and 24-month OS (94.3% vs 94.6%). The adverse events (AEs) observed in zanubrutinib versus BR were atrial fibrillation (3.3% vs 2.6%), bleeding (45.0% vs 11.0%), hypertension (14.2% vs 10.6%), infection (62.1% vs 55.9%), and neutropenia (15.8% vs 56.8%). Twenty patients in the zanubrutinib group and 31 in the BR group discontinued treatment due to AEs, leading to the death of 11 patients in each group.
The clinical observations with zanubrutinib demonstrate its clinical utility as a frontline treatment for treatment-naïve CLL/SLL patients.
Kahl BS, Giannopoulos K, Jurczak W, et al. CLL-137 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), Clin Lymphoma Myeloma Leuk 2022;22:S269-70.