ICML 2025 | Selecting between covalent and non-covalent BTK inhibitors for patients with MCL

So as we know there are covalent BTK inhibitors and non-covalent BTK inhibitors. Currently for the relapsed setting, the preferred treatment is still using one of the covalent BTK inhibitors such as acalabrutinib or zanubrutinib. In other parts of the world other than the US, ibrutinib is still available. The non-covalent BTK inhibitor pirtobrutinib is approved in a setting after prior exposure to covalent BTK inhibitor. So I would say in terms of choosing between these two categories of drugs, in the relapsed setting we still use covalent BTK inhibitor first as of today. But in the future when we incorporate the covalent BTK inhibitor into the frontline therapy, then in the second line the choice between covalent and the second generation non-covalent BTK inhibitor needs to take into consideration whether the patient was sensitive to the covalent BTK inhibitor in the frontline setting. For example, if they received a limited duration of covalent BTK inhibitor in the frontline setting and then remain in remission for let’s say over two years and then at the relapse time it’s certainly reasonable to re-expose them to covalent BTK inhibitor. But if they did not have that much of a response or progressed on the frontline BTK inhibitor then a non-covalent BTK inhibitor would be the choice in my opinion.

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