Dr Munir on the Efficacy of First-Line Zanubrutinib vs Acalabrutinib Plus Venetoclax in CLL

“What we found was that zanubrutinib was superior [to fixed-duration acalabrutinib plus venetoclax] in terms of PFS and OS, [at] a median follow-up of [approximately 40] months in both trials.”

Tahla Munir, MBChB, PhD, a consultant hematologist at Leeds Teaching Hospitals NHS Trust and deputy chair of the United Kingdom National Cancer Research Institute Chronic Lymphocytic Leukemia Study Group, detailed the efficacy of zanubrutinib (Brukinsa) as a first-line treatment for patients with chronic lymphocytic leukemia (CLL), as well as key considerations for its selection clinical practice.

A matching-adjusted indirect comparison (MAIC) of the phase 3 SEQUOIA (NCT03336333) and AMPLIFY (NCT03836261) trials demonstrated that the progression-free survival (PFS) and overall survival (OS) benefit with first-line zanubrutinib was superior to fixed-duration acalabrutinib (Calquence) plus venetoclax (Venclexta), with a median follow-up of 43.7 and 41.0 months in these respective studies, Munir began.

The open-label, randomized SEQUOIA trial evaluated the efficacy of zanubrutinib compared with bendamustine plus rituximab (Rituxan; BR) in patients with treatment-naive CLL or small lymphocytic lymphoma, which also included patients without 17p deletions (Cohort 1), and those with 17p deletions (Cohort 2 and Cohort 3). Patients on the study were randomly assigned 1:1 to receive zanubrutinib (arm A) or BR (arm B). Furthermore, the global, multicenter, open-label, randomized AMPLIFY trial assessed the efficacy and safety of fixed-duration acalabrutinib plus venetoclax compared with chemoimmunotherapy, consisting of either fludarabine, cyclophosphamide, and rituximab or BR, among patients with treatment-naive CLL without 17p deletions or TP53 mutation.

Without available clinical data, it’s necessary to evaluate patient characteristics before selecting therapies, particularly when comparing continuous therapy with fixed-duration therapy, Munir stated. He noted that the findings from the MAIC help inform decision-making by showing that continuous therapy has been shown to provide benefit in more patients, with fixed-duration treatment demonstrating slightly inferior PFS and OS outcomes. The MAIC established that these outcomes could contribute to individualized treatment selection, Munir concluded.