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EHA 2026 | Zanubrutinib vs ibrutinib: implications for frontline CLL management
Talha Munir, MBBS, MRCP, FRCPath, PhD, Leeds Teaching Hospitals NHS Trust, Leeds, UK, discusses a matching-adjusted indirect comparison evaluating zanubrutinib versus ibrutinib in treatment-naive chronic lymphocytic leukemia (CLL). He explores how outcomes with second-generation BTK inhibitors may influence the interpretation of fixed-duration versus continuous treatment strategies in contemporary clinical practice. This interview took place at the 31st Congress of the European Hematology Association (EHA) in Stockholm, Sweden.
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Transcript
So one of the main features, talking points about CLL treatment is the results of CLL-14, where fixed-duration approaches like venetoclax-ibrutinib, ibrutinib with venetoclax given in fixed-duration approaches, was compared to continuous ibrutinib therapy. So one of the criticisms of the study could be that a brutinib arm did really badly in that study, which was the standard arm in that study. And we now know that in real world, we are using second generation BTKI inhibitors as our main line of continuous therapy...
So one of the main features, talking points about CLL treatment is the results of CLL-14, where fixed-duration approaches like venetoclax-ibrutinib, ibrutinib with venetoclax given in fixed-duration approaches, was compared to continuous ibrutinib therapy. So one of the criticisms of the study could be that a brutinib arm did really badly in that study, which was the standard arm in that study. And we now know that in real world, we are using second generation BTKI inhibitors as our main line of continuous therapy. And the main endpoint of the study was at this moment in time was to look at non-inferiority at three years time point between continuous approaches versus the fixed duration approaches. So what we’ve tried to do here is to extrapolate the data for zanubrutinib and Sequoia study and use those patients’ data to replace the ibrutinib data in the CLL-14 and see if we can get the same results. And the results are different. And then ibrutinib-treated patients probably will be doing better as compared to ibrutinib-treated patients. This doesn’t come as a surprise to the majority of the people in the CLL community because ibrutinib use has declined over time due to the side effect profile. But it does raise important questions about the overall interpretation of the data where we’re using second generation BTKI inhibitors in the real world practice.
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