Class: Oral, FLT3 inhibitor (potent against FLT3-ITD and FLT3-TKD mutations)
Indication
- Relapsed or refractory AML with FLT3 mutation (ITD or TKD).
- Approved in adults.
- Not first-line outside of trials (though can be used in combination in frontline for older/unfit patients per trials).
Mechanism of Action: Inhibits mutant FLT3 receptor tyrosine kinase → reduces proliferation and survival of leukemic blasts.
Dose: 120 mg orally once daily (with or without food) until disease progression or unacceptable toxicity.
Key Adverse Effects
- Myelosuppression → anemia, neutropenia, thrombocytopenia
- QTc prolongation → monitor ECG regularly
- Differentiation syndrome (rare, but reported)
- Elevated liver enzymes (AST/ALT)
- Fatigue, diarrhea, nausea
Monitoring
- CBC frequently (especially early during therapy)
- LFTs
- Electrolytes
- ECG for QTc monitoring
- Monitor for differentiation syndrome (rare compared to IDH inhibitors)
Clinical Notes
- Gilteritinib has shown superior overall survival vs salvage chemotherapy in relapsed/refractory FLT3-mutated AML (ADMIRAL trial).
- Can be used as a bridge to allogeneic HSCT.
- Oral administration improves convenience and outpatient use.
- Summary:
Gilteritinib is an oral FLT3 inhibitor for relapsed/refractory FLT3-mutated AML. Key points: myelosuppression, QT prolongation, LFT monitoring, and potential differentiation syndrome.