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iwCLL 2025 | The comparative efficacy of zanubrutinib versus fixed-duration AV in frontline CLL
Talha Munir, MBBS, MRCP, FRCPath, PhD, Leeds Teaching Hospitals NHS Trust, Leeds, UK, discusses the findings of a matching-adjusted indirect comparison (MAIC) comparing the outcomes of patients with treatment-naïve chronic lymphocytic leukemia (CLL) treated with zanubrutinib in the SEQUOIA trial (NCT03336333) to patients treated with acalabrutinib plus venetoclax (AV) in the AMPLIFY trial (NCT03836261). This analysis demonstrated that continuous zanubrutinib treatment provided a progression-free survival (PFS) benefit over fixed-duration AV. This interview took place at the biennial International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2025 in Krakow, Poland.
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Transcript
In terms of a matched indirect comparison, the first thing to say is that that’s the second best form of evidence that we can get instead of a Phase III clinical trial. With the best will in the world, we won’t be able to get a very good Phase III clinical trial comparing continuous BTK inhibitor therapies to fixed-duration approaches. Although there are some trials which are looking at this question, the BTK inhibitors will be different in different trials...
In terms of a matched indirect comparison, the first thing to say is that that’s the second best form of evidence that we can get instead of a Phase III clinical trial. With the best will in the world, we won’t be able to get a very good Phase III clinical trial comparing continuous BTK inhibitor therapies to fixed-duration approaches. Although there are some trials which are looking at this question, the BTK inhibitors will be different in different trials.
This matched indirect comparison took patients who were treated with zanubrutinib on the SEQUOIA study and compared that to the A+V patients treated in the AMPLIFY study. They were matched appropriately, and there were different types of dissections that were done to make sure that the data is as robust as possible. As with any matched indirect comparison, the effective sample size reduces substantially, and as a result of that you have to take the evidence based on the data that we’ve got in front of us. What it shows is actually zanubrutinib given continuously was superior to acalabrutinib and venetoclax in terms of progression-free survival. So it is providing evidence that continuous therapy might appear to be a fixed-duration approach, and essentially hopefully with the coming trials in the future we might be able to get better information on these patients.
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