ICML 2025 | The current role of pirtobrutinib in CLL & looking beyond BTKis for patients who develop resistance

It’ll be interesting to see – so firm hold on third line plus right now to coexist with their label by the FDA that label has been updated with the BRUIN-321 study that included second-line patients. I am not so sure that I’m jumping into using a pirtobrutinib immediately second line for everyone I think venetoclax is a great treatment for patients that have seen covalent BTK first line. And I certainly at this point in time, I’m not wanting to use pirtobrutinib before a covalent BTK inhibitor. I believe the label still requires you to have seen a covalent BTK inhibitor at that point. But that’s a question that’s coming up. Will we eventually put pirtobrutinib ahead? But I need to see some more long-term data in terms of sequencing these treatments before I would feel comfortable with that. Looking beyond pirtobrutinib and other ways we can attack BTK, of course, degraders are of interest. And are these going to be effective against more patients that have become resistant to, say, acalabrutinib and zanubrutinib, which we are recognizing have different mechanisms in certain ways of how they are becoming resistant to BTK with gatekeeper and kinase dead mutations that degraders seem to be more active against. So will we need to ultimately move on from a non-covalent like pirtobrutinib to utilize a degrader that’s more active or will we save degraders for if pirtobrutinib doesn’t work? I think at the end of the day, if we create enough viable lines of therapy for our CLL patients, most will always have an option. You’ll have very few that sort of run out of options, if you will.

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