In a recent study, Adam Kittai, MD, Division of Hematology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, and colleagues analyzed the clinical outcomes of patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) treated with acalabrutinib and zanubrutinib.

They presented their findings at the 2023 ASCO Annual Meeting in Chicago, IL.
Although previous trials compared the current standard of care (ibrutinib) with acalabrutinib and zanubrutinib individually, the two second-generation Bruton tyrosine kinase inhibitors were not directly compared. Using an unanchored matching adjusted indirect comparison (MAIC), the researchers of the current study were able to evaluate the efficacy and safety of zanubrutinib and acalabrutinib using the ALPINE (aggregate data) and ASCEND (individual patient data [IPD]) trials, respectively.

This methodology reduced the differences in variables between the two studies that would have affected progression-free survival (PFS) so Dr Kittai and colleagues could conduct an exploratory multivariate Cox regression analysis of the ASCEND IPD (acalabrutinib). The variables included deletion 11q, deletion 17p, IGHV status, age, sex, region, and Rai stage. They also set a date cut-off of February 21, 2020, for acalabrutinib data so they could compare the incidence of adverse events (AEs) with the zanubrutinib group to match the median treatment exposure of 28.4 months. By using Kaplan-Meier curves, researchers obtained pseudo IPD for zanubrutinib to compare investigator-assessed (INV) PFS for ALPINE (zanubrutinib) and ASCEND (acalabrutinib).

After the statistical adjustments, the 12-month INV PFS for acalabrutinib and zanubrutinib were similar (91 [95% confidence interval (CI), 84-95] for acalabrutinib vs 92 [95% CI, 88-94] for zanubrutinib), as were the 24-month INV PFS (76 [95% CI, 66-84] vs 78 [95% CI, 73-83], respectively). In addition, the MAIC hazard ratio (HR) for INV PFS was similar for both (HR, 0.90; 95% CI, 0.56-3.08), as was the risk of having a grade 3 or higher AE, atrial fibrillation, or an AE leading to discontinuation, among other comparators. However, some measures were lower with acalabrutinib compared to zanubrutinib, including the risk of having a serious AE (odds ratio [OR], 0.61; 95% CI, 0.39-0.97) or an AE leading to dose reduction (OR, 0.30; 95% CI, 0.14-0.67). Acalabrutinib also showed a lower risk for grade 3 or higher hemorrhage, and any grade and grade 3 or higher hypertension.

Ultimately, the analysis did show comparable efficacy for zanubrutinib and acalabrutinib in patients with R/R CLL. The researchers mentioned that their study was mostly hypothesis generating because of the limitations of MAIC analyses. 

Source:

Kittai A, Skarbnik A, Miranda M, et al. A matching-adjusted indirect comparison (MAIC) of the efficacy and safety of acalabrutinib (acala) versus zanubrutinib (zanu) in relapsed or refractory chronic lymphocytic leukemia (RR CLL); June 2-6, 2023; Chicago, IL, and virtual; Abstract 7540.