SOHO 2023 | The future of menin inhibitors in AML

So menin inhibitors are the newest targeted therapy that we’re using in acute myeloid leukemia, and I predict that menin inhibitors will be used as standard treatment for acute myeloid leukemia. We’re likely going to see more of those either in combination or as a single agent. I’m going to talk today about the future of menin inhibitors- this involves the genotypes that are being investigated now. So this is leukemias that have the KMT2A rearrangement, which is a fusion that is usually resistant to treatment- and the most common mutation in AML, NPM1, and probably some other genotypes that we’re going to investigate. We will probably test menin inhibitors in combination with multiple other agents, either chemotherapy or targeted therapies. What we’ve learned so far about menin inhibitors is that the interaction of menin and KMT2A is very important for a lot of leukemias. It may not be these drugs that we have now, it may be future drugs that target it or combinations that will target it better- but this is where we’re headed. Currently they’re being studied in relapsed/refractory leukemia, and I suspect for KMT2A-rearranged leukemias they would be used as single agents until we have more data on combination. For NPM1, there are more options because of the co-mutation status. I think when the FLT3 variant allele frequency is high, it’s reasonable to use a FLT3 inhibitor, even if they have been treated with a prior FLT3 inhibitor. But if it’s a FLT3-TKD, or the variant allele frequency is low, or patients have had multiple FLT3 inhibitors, I think my impression based on preclinical data for now, is that menin inhibition is the next best option.