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EHA 2026 | Sequencing covalent and non-covalent BTK inhibitors in MCL
In this video, Nirav Niranjan Shah, MD, Medical College of Wisconsin, Milwaukee, WI, briefly discusses the sequencing of covalent and non-covalent BTK inhibitors (BTKis) in the treatment of mantle cell lymphoma (MCL). Dr Shah notes that the current paradigm will be covalent BTKi treatment before a non-covalent BTKi until ongoing trials provide valuable insights into the optimal sequencing of these agents. This interview took place at the 31st Congress of the European Hematology Association (EHA) in Stockholm, Sweden.
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Transcript
So at this time, we sort of have a sequencing issue, right? We know that covalent inhibitors are approved and effective, and we have durable data for them. And we know that non-covalent inhibitors work after covalent inhibitors. And so do we want to sort of pull the trigger and give a non-covalent inhibitor first, or do we wait for them to relapse? I think at the end of the day, research will help us determine the answer to this...
So at this time, we sort of have a sequencing issue, right? We know that covalent inhibitors are approved and effective, and we have durable data for them. And we know that non-covalent inhibitors work after covalent inhibitors. And so do we want to sort of pull the trigger and give a non-covalent inhibitor first, or do we wait for them to relapse? I think at the end of the day, research will help us determine the answer to this. And so there’s an ongoing trial comparing pirtobrutinib, a non-covalent BTK inhibitor, to the covalent BTK inhibitors in MCL, in relapsed MCL. When that study reads out, you might actually learn that a non-covalent inhibitor is a better strategy to use before a covalent inhibitor. Until we have data like that, I think that the current paradigm will be covalent inhibitors as part of the front or second line, and then non-covalent inhibitors are sort of a later line therapy.
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