ASH 2025 | Strategies to further deepen responses to menin inhibitors in AML

We are really excited about having another targeted therapy available for our patients, mostly because nucleophosmin 1 or NPM1 mutations represent a substantial population or subgroup, at least 30 to 40% of patients. The KMT2A rearranged group represents like barely 10%, but we have more targetable patients. I agree that with monotherapy, the response rate is not as exciting as we’d like it to be. It’s about on par with the other targeted single agent therapies, as a reminder. So with IDH1 inhibitors, FLT3 inhibitors, the monotherapy response rate is roughly 20% to 30% on its own. So it meets the expectations of the existing approved monotherapies. I agree that that response rate is not high enough, but if you had a frail patient who had seen multiple lines of therapy or is much older, it represents an option for a single therapy. For patients that are a bit more robust, thankfully there are now combination studies with doublets or triplet regimens for us to understand how we can further broaden response, especially because there are co-mutations that need to be addressed. So having combination therapies will help to address that and expansion of those clones. But it also might help to deepen responses. So I agree that the future of the menin will include really novel combinations with other small molecules, combinations with hypomethylating agent venetoclax backbones, and even evaluation with intensive chemotherapy. I am very excited about the menin space. We have several different options in play, two drugs already approved. I think this is an arena that will be amplified and serve as a good backbone.

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