Ziftomenib — Drug Monograph
Brand names: Komzifti
Drug class: Other
Mechanism of Action
Oral menin inhibitor that disrupts the protein-protein interaction between menin (encoded by MEN1) and KMT2A (MLL1) in the nucleus. Menin acts as an essential oncogenic cofactor for KMT2A-driven transcription in NPM1-mutated AML and KMT2A-rearranged AML, upregulating HOXA/B cluster genes and MEIS1. Blocking this interaction suppresses oncogenic transcription and induces myeloid differentiation. First FDA-approved menin inhibitor.
FDA Indications
- Relapsed or refractory NPM1-mutated acute myeloid leukemia (AML) in adults (FDA approved 2025; KOMET-007 Phase 1/2: 35% CR+CRi rate)
Common Side Effects
- Nausea (28%)
- Differentiation syndrome symptoms (fever, edema)
- Fatigue (22%)
- QTc prolongation
- Diarrhea (18%)
- Leukocytosis
- Musculoskeletal pain
- Elevated liver enzymes
Clinical Pearl
Ziftomenib is the first FDA-approved menin inhibitor and the first therapy targeting the menin-KMT2A interaction. Differentiation syndrome is the most critical safety concern and may be more severe than that seen with IDH inhibitors, requiring proactive corticosteroid prophylaxis consideration and immediate treatment. NPM1 mutation testing is mandatory before initiation.
Related Therapies & Mechanisms
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- Glasdegib (Daurismo) — Other · Leukemia