Revumenib (Revuforj®): A Comprehensive Monograph on the First-in-Class Menin Inhibitor for the Treatment of Acute Leukemias

I. Executive Summary

Revumenib, marketed under the brand name Revuforj®, is a first-in-class, orally bioavailable, small-molecule antineoplastic agent that functions as a potent and selective menin inhibitor.[1] Its development marks a significant advancement in the targeted therapy of acute leukemias characterized by specific genetic alterations. The drug is designed to disrupt the critical protein-protein interaction between menin and the lysine methyltransferase 2A (KMT2A, also known as MLL) protein or its oncogenic fusion variants. This interaction is a key driver of leukemogenesis in acute leukemias harboring

KMT2A gene rearrangements (KMT2Ar) or mutations in the nucleophosmin 1 (NPM1) gene (NPM1m).[1]

On November 15, 2024, the U.S. Food and Drug Administration (FDA) granted approval to Revumenib for the treatment of adult and pediatric patients aged one year and older with relapsed or refractory (R/R) acute leukemia featuring a KMT2A translocation.[7] This regulatory milestone was based on the compelling efficacy and safety data from the pivotal Phase I/II AUGMENT-101 clinical trial. In a heavily pretreated population of patients with KMT2Ar acute leukemia, Revumenib monotherapy demonstrated clinically meaningful and durable responses. The trial met its primary endpoint with a complete remission (CR) plus CR with partial hematologic recovery (CR+CRh) rate of 21.2% and an overall response rate (ORR) exceeding 60%.[10]

The safety profile of Revumenib is considered manageable, though it includes significant risks that require careful clinical oversight. The drug's prescribing information includes a boxed warning for Differentiation Syndrome (DS), a potentially fatal on-target toxicity. Another major risk is QTc interval prolongation, necessitating baseline and routine electrocardiogram (ECG) monitoring.[1]