EHA 2024 | Immunophenotypic changes induced by menin inhibition in AML

So menin inhibitors are a novel class of agents that obviously disrupt the menin-KMT2A interaction in leukemias, and there are certain genotypes that are susceptible to menin inhibition, including one of the most common mutations in AML that is NPM1, and then also other more rare subtypes like KMT2A-rearranged NUP98-rearranged AMLs. So we looked at immunophenotypic changes that are induced by menin inhibition in the setting of acute myeloid leukemia, and the reason for that is that menin inhibitors are differentiating agents, so they induce differentiation. And that creates, you know, somewhat of a challenge in our practice where we look for AML MRD or measurable residual acute myeloid leukemia by flow cytometry because the phenotypic changes that are induced by the therapy can somewhat make our interpretation challenging. And so we’ve characterized this in the setting of revumenib monotherapy in patients with relapsed and refractory acute myeloid leukemias and showed that there’s a substantial subset of patients that actually show a phenotypic shift, either going from a more myeloid stem-like phenotype at baseline to a more monocytic mature phenotype or vice versa. So it’s actually not always the same, and they can actually relapse with a different phenotype as well. So very important to be aware of in terms of AML MRD detection by flow cytometry.