Mechanism:
A multi-targeted kinase inhibitor that primarily blocks FLT3 (FMS-like tyrosine kinase 3), along with KIT, PDGFR, and VEGFR.
Approval: FDA-approved for:
- FLT3-mutated AML (in combination with chemotherapy for newly diagnosed patients).
- Aggressive systemic mastocytosis (ASM).
Key Features in AML
- Target Population:
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- Newly diagnosed FLT3-mutated AML (both FLT3-ITD and FLT3-TKD).
- Used in induction, consolidation, and maintenance (with chemotherapy).
- Combination Therapy:
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- Given with standard 7+3 induction (cytarabine + daunorubicin) and high-dose cytarabine consolidation.
- Continued as maintenance therapy in eligible patients.
- Efficacy:
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- Improves overall survival (OS) and event-free survival (EFS) vs. chemo alone.
- Landmark trial (RATIFY): Median OS = 74.7 months (vs. 25.6 months with placebo + chemo).
Mechanism of Action
- Inhibits FLT3 signaling → blocks proliferation and survival of leukemia cells.
- Also targets KIT (relevant in core-binding factor AML) and other kinases.
Side Effects
- Myelosuppression (neutropenia, anemia, thrombocytopenia).
- GI effects (nausea, vomiting, diarrhea).
- Pulmonary toxicity (rare but serious; monitor for pneumonitis).
Key Takeaways
- First FLT3 inhibitor approved for AML (now standard of care in FLT3-mutated AML).
- Used with chemotherapy, not as monotherapy.
- Gilteritinib (a next-gen FLT3 inhibitor) is preferred for relapsed/refractory FLT3+ AML
Synonyms
Rydapt