Dr Munir on a MAIC of Zanubrutinib vs Fixed-Duration Acalabrutinib Plus Venetoclax in CLL

“A matching-adjusted indirect comparison is always going to be fraught with some issues because we are comparing data from different trials. The methodology [of this analysis] is examining patient-level data from SEQUOIA and comparing it with publicized data from AMPLIFY.”

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, discussed the rationale for a matching-adjusted indirect comparison (MAIC) of the phase 3 SEQUOIA (NCT03336333) and AMPLIFY (NCT03836261) trials in patients with chronic lymphocytic leukemia (CLL).

Munir began by noting that investigators must be careful when interpreting results from an MAIC as this type of analysis compares data from multiple clinical trials. In this MAIC, investigators examined clinically significant variables between the 2 studies to accurately match patients, he added. Once this comparison bank is established, the study authors were able to create an effective sample size, he noted. As a result, they were able to make progression-free survival (PFS) and overall survival adjustments and draw conclusions with the indirect comparison, he said.

Findings from the MAIC presented during the 2025 ASCO Annual Meeting demonstrated that, at a median follow-up of 43.7 months for patients in SEQUOIA and 41.0 months for those in AMPLIFY, the population-adjusted investigator-assessed progression-free survival (PFS) favored treatment with zanubrutinib (Brukinsa) in SEQUOIA vs fixed-duration acalabrutinib(Calquence) plus venetoclax (Venclexta) in AMPLIFY (HR, 0.26; 95% CI, 0.13-0.54; P < .0003). The 36-month PFS rates after matching in the SEQUOIA (n = 126) and AMPLIFY (n = 581) cohorts were 88.5% and 76.5%, respectively.

After matching, the baseline characteristics were well balanced between SEQUOIA and AMPLIFY. The percentage of patients who were older than 65 years, male, had and ECOG performance status of 0 or 1, had deletion 11q mutations, and unmutated IGHV were all identical, at 26.8%, 64.5%, 91.8%, 17.6%, and 58.6%, respectively.