SOHO 2025 | The future of menin inhibition in AML: combination strategies

The future is in combination. And the reason is for what I said a couple of minutes ago, whereas the single agent in relapsed/refractory disease, you get high response rates, but the duration of response is relatively short. So one way to fix that problem is to combine an active drug with standard of care therapies. There are already a number of phase I or phase II trials that are combining revumenib or other menin inhibitors with standard of care intensive chemotherapy, like 7 plus 3, and also with standard of care lower intensity therapy like azacitidine and venetoclax. In fact, those trials are so far along that I think every company who has a menin inhibitor, the majority of companies that have a menin inhibitor have invested heavily in performing randomized Phase III studies to see whether the combination of AZA-VEN and menin inhibitors better than AZA-VEN as a doublet and whether the combination of revumenib or other menin inhibitors with intensive chemotherapy is better than intensive chemotherapy alone. I mean, the last thing I’ll say about this is that we’re now talking about doing quadruplet studies, because we now have targeted therapies that can potentially be combined. So for example, if you had a patient with a co-occurring NPM1 and FLT3 mutation, there’s actually a study up and running out of the Dana-Farber Cancer Institute that’s combining 7 and 3 midostaurin, the FLT3 inhibitor, with revumenib for NPM1 mutant disease. So we’re going to be seeing, I think, a lot of these studies that are trying to mix and match a lot of agents together. And the question is going to be, what’s the best way to do that? What are the response rates? How do you tease out the components of each drug and which one is most important? But I think that’s provided a lot of things for us to do over the next two to five years.

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