Pharmacological Class
- Protein synthesis inhibitor (not a TKI)
- Semisynthetic formulation of homoharringtonine (plant alkaloid from Cephalotaxus species).
Mechanism of Action
- Binds to the A-site cleft of the ribosomal 80S subunit.
- Interferes with elongation of protein synthesis → inhibition of oncogenic proteins (including BCR-ABL) and induction of apoptosis.
- Works independently of BCR-ABL kinase activity, therefore effective in TKI-resistant CML, including T315I mutation.
Indications (FDA-approved)
- Chronic myeloid leukemia (CML), chronic or accelerated phase
- In adults with resistance and/or intolerance to ≥2 TKIs.
Dosing
- Induction phase:
- 1.25 mg/m² subcutaneously twice daily (BID) × 14 consecutive days of a 28-day cycle.
- Maintenance phase:
- 1.25 mg/m² SC BID × 7 consecutive days of a 28-day cycle.
- Continue until progression or unacceptable toxicity.
Adverse Effects
- Hematologic (most common):
- Thrombocytopenia, neutropenia, anemia (often severe).
- Non-hematologic:
- Diarrhea, nausea, fatigue, injection site reactions, fever.
- Serious risks:
- Myelosuppression-related infections/bleeding.
Monitoring
- CBC with differential:
- Weekly during induction, then every 2 weeks or as clinically indicated.
- Blood glucose: can worsen hyperglycemia.
- Signs of infection/bleeding due to cytopenias.
Drug Interactions
- Not a CYP450 substrate.
- Few drug–drug interactions compared to TKIs.
- But additive myelosuppression possible with other agents.
Clinical Pearls
- Route: only TKI-refractory CML drug given subcutaneously.
- Niche role: Used when multiple TKIs have failed or when T315I mutation is present and ponatinib is not tolerated/appropriate.
- Responses are often hematologic and sometimes cytogenetic, but complete molecular remissions are less common compared to TKIs.
- High monitoring burden due to cytopenias.
Key exam point:
- Omacetaxine = not a TKI, protein synthesis inhibitor → retains activity in T315I mutation CML, given SC BID in cycles, with major toxicity = severe myelosuppression.