Matching Analysis Compares Zanubrutinib With Acalabrutinib in Patients With CLL

When compared with acalabrutinib, zanubrutinib showed advantages in progression-free survival (PFS) and complete response (CR) rates with potentially improved overall survival (OS) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), according to a matching analysis presented at the 28th International Congress on Hematologic Malignancies® held in Miami, Florida.

The study, led by Mazyar Shadman, MD, MPH, of the Fred Hutchinson Cancer Center, compared the efficacy of zanubrutinib in the ALPINE trial with acalabrutinib in the ASCEND trial using matching-adjusted indirect comparison (MAIC) methodology.

A total of 155 patients received acalabrutinib in the ASCEND trial, while 327 patients received zanubrutinib in the ALPINE trial. Using a weighted Cox proportional hazard model, the authors compared the PFS and OS of the two therapies. They also used a weighted logistic regression model to compare CR.

The following were identified as prognostic factors or predictors of treatment effect for matching:

• Age
• Gender
• ECOG performance status
• Geographic region
• Mutated IGHV, del(17p), del(11q) and TP53 mutation status
• Complex karyotype
• Bulky disease
• Cancer type
• Beta₂-microglobulin
• Rai/Binet stage
• Number and type of prior therapies
• Absolute lymphocyte and neutrophil counts
• Platelet count

The researchers compared treatment effects in both the unadjusted population and the base-case adjusted population (See TABLE 1).

TABLE 1: Treatment Effects for Unadjusted, Base-Case Populations

Results for the sensitivity analyses were consistent with that of the base-case population.

The analysis did not compare the safety profiles of zanubrutinib and acalabrutinib, due to varying treatment exposure times across the two trials.

“While MAICs provide a scientific basis for evaluating hypotheses with regards to treatment efficacy across trials, the gold standard for evaluating evidence of relative efficacy remains randomized controlled trials,” wrote Dr. Shadman and colleagues.

Reference

Shadman M, Brown J, Williams R, et al. “Efficacy of zanubrutinib versus acalabrutinib in the treatment of relapsed or refractory chronic lymphocytic leukemia (R/R CLL): a matching-adjusted indirect comparison (MAIC).” Presented at the 28th International Congress on Hematologic Malignancies; , 2024; Miami, Florida.