Efficacy of zanubrutinib versus acalabrutinib for relapsed or refractory chronic lymphocytic leukemia (R/R CLL): a matching-adjusted indirect comparison (MAIC)
Mazyar Shadman, Jennifer R. Brown, Rhys Williams, Leyla Mohseninejad, Keri Yang, P. Rakonczai, Nicole Lamanna, Sheng Xu, Aileen Cleary Cohen, Susan O’Brien, Alessandra Tedeschi, Constantine S. Tam
Abstract
Background: There are no head-to-head studies comparing the efficacy of the Bruton tyrosine kinase inhibitors, zanubrutinib and acalabrutinib, in relapsed or refractory chronic lymphocytic leukemia (R/R CLL). Objective: To compare the relative efficacy of zanubrutinib and acalabrutinib in R/R CLL using indirect treatment comparison. Design: An unanchored matching-adjusted indirect comparison (MAIC) was performed. Methods: Individual patient-level data from ALPINE (zanubrutinib) were reweighted using prognostic/effect-modifying variables to match aggregate data from ASCEND (acalabrutinib). MAIC outcomes included investigator-assessed progression-free survival (PFS-INV), overall survival (OS), and complete response (CR). Results: Post-matching, PFS-INV was improved significantly for zanubrutinib versus acalabrutinib (hazard ratio (HR) = 0.68 (95% confidence interval (CI): 0.46–0.99); p = 0.0448) and OS showed a trend toward improvement for zanubrutinib (HR = 0.60; 95% CI: 0.35–1.02, p = 0.0575). CR was significantly higher for zanubrutinib versus acalabrutinib (odds ratio = 2.90 (95% CI: 1.13–7.43); p = 0.0270). Conclusion: Zanubrutinib was associated with a significant PFS-INV and CR advantage over acalabrutinib, with a trend toward improvement in OS.