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ICML 2025 | Safety and efficacy of pirtobrutinib in patients with covalent BTKi-intolerant B-cell malignancies
In this video, Nirav Shah, MD, Medical College of Wisconsin, Milwaukee, WI, comments on the safety and efficacy of pirtobrutinib monotherapy in patients with B-cell malignancies who are intolerant to covalent BTK inhibitors. Dr Shah highlights that pirtobrutinib’s non-covalent mechanism and precise targeting minimize off-target effects, providing a feasible option for patients who develop intolerance to other BTK inhibitors. This interview took place during the 18th International Conference on Malignant Lymphoma (18-ICML) in Lugano, Switzerland.
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Transcript
Yeah, so pirtobrutinib is a non-covalent BTK inhibitor. It has a different mechanism than some of the other BTK inhibitors which are covalent inhibitors. Pirtobrutinib also has very precise targeting, really doesn’t have a lot of off-target sort of effects and as a result has a really clean safety profile and we know there’s some patients that just have intolerance to covalent inhibitors...
Yeah, so pirtobrutinib is a non-covalent BTK inhibitor. It has a different mechanism than some of the other BTK inhibitors which are covalent inhibitors. Pirtobrutinib also has very precise targeting, really doesn’t have a lot of off-target sort of effects and as a result has a really clean safety profile and we know there’s some patients that just have intolerance to covalent inhibitors. So this was sort of a subset of the BRUIN data. Looking at those patients who had to stop their other BTK because of intolerance and then went on to pirtobrutinib. And what we found is that many of those patients could tolerate pirtobrutinib. And in fact, no patient stopped pirtobrutinib for the same reason they had to stop the other BTK inhibitor. And so this basically demonstrates that pirtobrutinib is a feasible option in the setting of intolerance because you won’t see the same side effect profile. And then those that did have toxicities, it tended to be lower grade toxicities than they saw with their other covalent inhibitor. So this provides some real evidence that pirtobrutinib is an option in that scenario.
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