revumenib — Drug Monograph
Brand names: Revuforj
Drug class: Other
Mechanism of Action
Revumenib is a potent, selective small-molecule inhibitor of the protein–protein interaction between menin and the KMT2A (MLL1) histone methyltransferase. In AML driven by KMT2A rearrangements or NPM1 mutations, the menin–KMT2A complex acts as a master transcriptional co-activator of HOXA/HOXB cluster genes and MEIS1, maintaining a leukemic stem cell program. By occupying the KMT2A-binding pocket on menin, revumenib disrupts oncogenic transcriptional complexes at these loci, downregulates HOXA/HOXB/MEIS1 expression, and induces myeloid differentiation of leukemic blasts.
FDA Indications
- Relapsed or refractory acute leukemia with a KMT2A (MLL) rearrangement or NPM1 mutation in adults and pediatric patients ≥1 year — approved Nov 2023 (AUGMENT-101 trial)
Common Side Effects
- Differentiation syndrome (~27%)
- Nausea
- Mucositis / stomatitis
- Diarrhea
- Elevated transaminases
- Febrile neutropenia
- Hyperbilirubinemia
- QTc prolongation
- Fatigue
- Hemorrhage
- Leukocytosis (differentiation)
- Edema
Clinical Pearl
Revumenib is the first menin inhibitor to receive FDA approval, representing a mechanistically distinct therapeutic approach for genetically defined AML subsets. Because KMT2A-rearranged and NPM1-mutated AMLs share a dependency on HOXA/HOXB/MEIS1 transcriptional programs driven by the menin–KMT2A axis, revumenib addresses both genetic subtypes with a single targeted mechanism. Azole antifungal prophylaxis — nearly universal in AML patients — is a strong CYP3A4 inhibitor and requires revumenib…
Related Therapies & Mechanisms
- Arsenic Trioxide (Trisenox) — Other · Leukemia
- Brexucabtagene autoleucel (Tecartus) — Other · Leukemia
- Enasidenib (Idhifa) — Other · Leukemia
- Glasdegib (Daurismo) — Other · Leukemia