Tahla Munir, MBChB, PhD, is 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, in Leeds, UK.

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 

 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; 

 < .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 

 were all identical, at 26.8%, 64.5%, 91.8%, 17.6%, and 58.6%, respectively.

Videos

Tahla Munir, MBChB, PhD, discusses the rationale for a MAIC of the phase 3 SEQUOIA and AMPLIFY trials in chronic lymphocytic leukemia.

Presented by Tahla Munir, MBBS, this matching-adjusted indirect comparison demonstrated a significant progression-free survival advantage for zanubrutinib over fixed-duration acalabrutinib plus venetoclax in low-risk, treatment-naive chronic lymphocytic leukemia, with a 36-month PFS rate of 88.5% vs 77%, respectively.

Comparative Efficacy of Zanubrutinib versus Fixed-Duration Acalabrutinib Plus Venetoclax for First-Line Treatment of Chronic Lymphocytic Leukemia (CLL): A Matching-Adjusted Indirect Comparison (MAIC)

Presented by Talha Munir, MBChB, PhD, this matching-adjusted indirect comparison demonstrated a significant progression-free survival advantage for zanubrutinib over fixed-duration acalabrutinib plus venetoclax in low-risk, treatment-naive chronic lymphocytic leukemia, with a 36-month progression-free survival rate of 88.5% vs 77%, respectively.

Comparative Efficacy of Zanubrutinib vs Fixed-Duration Acalabrutinib Plus Venetoclax for First-Line Treatment of Chronic Lymphocytic Leukemia (CLL): A Matching-Adjusted Indirect Comparison (MAIC)

Tahla Munir, MBChB, PhD, details the efficacy of first-line zanubrutinib and clinical implications for treatment selection in CLL.

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 

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.

utinib vs. Acalabrutinib in B-Cell Malignancies: An Adverse Event-Based Economic Analysis

An economic analysis of Zanubrutinib versus Acalabrutinib and associated QoL benefits in AE management in patients with B-cell malignancies.

Talha Munir, MBChB, PhD

Articles

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

Comparative Efficacy of Zanubrutinib vs Fixed-Duration Acalabrutinib Plus Venetoclax for First-Line Treatment of Chronic Lymphocytic Leukemia (CLL): A Matching-Adjusted Indirect Comparison (MAIC)

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

Zanubrutinib vs. Acalabrutinib in B-Cell Malignancies: An Adverse Event-Based Economic Analysis