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ISAL 2025 | Adverse events to look out for when treating AML with menin inhibitors
Florian Perner, MD, Hannover Medical School, Hannover, Germany, comments on the adverse events (AEs) associated with menin inhibitors in acute myeloid leukemia (AML). He notes that common events include infections and cytopenias, as well as QT time prolongation, which is a drug-specific AE particularly associated with revumenib. Additionally, menin inhibitors can cause differentiation syndrome, a cytokine release syndrome. This interview took place at the 19th International Symposium on Acute Leukemias (ISAL XIX) in Munich, Germany.
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Transcript
In this heavily pretreated patient clientele that is subjected to these trials right now, we have common adverse events like infections and cytopenias which we simply see in such a heavily pretreated patient clientele. But it’s not completely clear yet how these adverse events are directly related to the drug. Regarding the drug-specific adverse events of the menin inhibitors themselves, there is, with revumenib specifically, QT time prolongation is an issue and that is something that has limited dose escalation in this patient cohort and it is something that needs to be monitored, particularly when patients get set on the drug...
In this heavily pretreated patient clientele that is subjected to these trials right now, we have common adverse events like infections and cytopenias which we simply see in such a heavily pretreated patient clientele. But it’s not completely clear yet how these adverse events are directly related to the drug. Regarding the drug-specific adverse events of the menin inhibitors themselves, there is, with revumenib specifically, QT time prolongation is an issue and that is something that has limited dose escalation in this patient cohort and it is something that needs to be monitored, particularly when patients get set on the drug. Interestingly, this adverse event does not seem to occur with other menin inhibitors. So that is definitely one difference. But all of those inhibitors to a different degree though, as a monotherapy, can cause differentiation syndrome. Which is a cytokine release syndrome that is caused by the inhibitor kick-starting differentiation of these leukemic blasts, and particularly in patients with very high leukemia burdens that get treated under monotherapy, this is a significant risk and has led to fatalities in the past. We do expect though that in future trials, where it’s combined with chemotherapy, this issue will probably be much less likely to occur.
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