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ASH 2025 | Combination regimens to address resistance to menin inhibitors in AML
Jacqueline Garcia, MD, Dana Farber Cancer Institute, Boston, MA, comments on the importance of strategic combination regimens to address resistance and deepen response in patients with acute myeloid leukemia (AML) receiving menin inhibitors. Dr Garcia emphasizes the potential benefits of combining menin inhibitors with other novel therapies to prevent or address resistance. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
What we’re learning right now is there’s several types of mutations, some that are acquired at the time of treatment or some that were underlying and that expand. I do think that offering a tolerable type of regimen, whether it’s single agent or combination, more likely combination in this scenario, would allow for deepening response, which could prevent resistance. Part of the challenges for MEN1 resistance to occur, one of the possibilities is if you’re offering intermittent therapy...
What we’re learning right now is there’s several types of mutations, some that are acquired at the time of treatment or some that were underlying and that expand. I do think that offering a tolerable type of regimen, whether it’s single agent or combination, more likely combination in this scenario, would allow for deepening response, which could prevent resistance. Part of the challenges for MEN1 resistance to occur, one of the possibilities is if you’re offering intermittent therapy. So when thinking about combinations, you have to be very strategic, because if you’re continuously starting and stopping the menin inhibitor, that might also amplify the possibility of a MEN1 mutation. So I do think that combination helps to address resistance and preventing it by deepening the response, deepening the residual disease, and allowing for eradication of potential clones. I do think we need to be very strategic about how these combination drugs are given because on and off effect may become a problem if drugs are not tolerable because of cytopenias or low blood counts or complications like infections. I do think that there are going to be opportunities based on some phenomenal work that lab investigators are working on to look at opportunities to combine menin with other novel therapies to try to address the potential for resistance or to prevent it.
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