Abstract
Background Revumenib is a first-in-class oral inhibitor of the menin–KMT2A protein–protein interaction, approved by the United States Food and Drug Administration in November 2024 for relapsed or refractory acute leukemia with a KMT2A translocation and in October 2025 for relapsed or refractory acute myeloid leukemia with a susceptible NPM1 mutation. The registrational programme identified differentiation syndrome (and QTc-interval prolongation as adverse events of special interest. The post-marketing adverse-event experience has not been systematically characterized. Methods A retrospective disproportionality analysis of the FDA Adverse Event Reporting System (FAERS, 14,104,743 reports) was performed, restricted to reports in which revumenib was named as a primary or secondary suspect product (n = 283). Frequentist (proportional reporting ratio with Pearson χ²; reporting odds ratio with 95% confidence interval) and Bayesian (information component with lower 2.5% bound; empirical Bayes geometric mean with lower 5% bound) metrics were calculated for every adverse event reported in association with the drug. A signal required more than three reports together with concurrent fulfilment of all four disproportionality criteria. Results Twenty-eight adverse events were evaluated; nineteen met the signal definition. Differentiation syndrome produced the strongest disproportionality (EBGM 15.38, EBGM₀₅ 9.17). Cytopenias of every lineage, electrocardiogram QT prolonged (EBGM₀₅ 3.67), and lower-magnitude constitutional and gastrointestinal events were also signalled. Nine events did not constitute signals, principally because of the case-count threshold. Conclusion Post-marketing reporting corroborates the safety profile established in AUGMENT-101 and identifies no novel toxicity category.