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ESH CLL 2026 | Non-covalent BTK inhibitors in CLL: activity after covalent BTK inhibitors
Romain Guièze, MD, PhD, CHU Clermont Ferrand, Clermont Ferrand, France, discusses the role of non-covalent BTK inhibitors in chronic lymphocytic leukemia (CLL), highlighting their activity in patients previously treated with covalent BTK inhibitors and their promising safety profile, while noting ongoing questions about resistance and optimal treatment sequencing. This interview took place at the ESH CLL 2026 congress in Stockholm, Sweden.
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Transcript
What we know is that the non-covalent BTK inhibitors are effective on patients previously exposed to covalent BTK inhibitors because they are active and not dependent on this C481 residue. So the non-covalent after covalent is already something. We have enough evidence to claim that it is effective. So, what is interesting with the non-covalent is not only their efficacy in previously treated patients by BTK inhibitors, but also their safety profile...
What we know is that the non-covalent BTK inhibitors are effective on patients previously exposed to covalent BTK inhibitors because they are active and not dependent on this C481 residue. So the non-covalent after covalent is already something. We have enough evidence to claim that it is effective. So, what is interesting with the non-covalent is not only their efficacy in previously treated patients by BTK inhibitors, but also their safety profile. So we now have data for patients treated with this kind of compound, such as the pirtobrutinib, in the frontline setting. And so it looks like the safety profile is really impressive. But one of the questions is that if we do this kind of approach, do we have a risk of resistance mutation to BTK that will affect the subsequent treatment with covalent BTKI? So that’s one of the questions that is remaining to answer within the next future. But we have plenty of drugs and therapeutic sequencing is expected to be very effective in CLL.
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