Azacitidine

Azacitidine is a hypomethylating agent (HMA) used to treat myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), particularly in older/unfit patients.

Key Features:

• Mechanism:
  • Inhibits DNA methyltransferase (DNMT) → reverses aberrant DNA hypermethylation → restores normal gene expression.
• Also incorporates into RNA → disrupts protein synthesis.
• Approved Uses:
  • MDS (all subtypes, including high-risk).
  • AML (with 20-30% blasts or therapy-related AML, often combined with venetoclax)
• Administration:
  • Subcutaneous or IV, typically in 7-day cycles (28-day schedule).

Efficacy:

• Improves overall survival vs. supportive care in MDS/AML.
• Combination with venetoclax doubles response rates in AML (CR/CRi ~60-70%).

Side Effects:

• Myelosuppression (neutropenia, thrombocytopenia).
• GI toxicity (nausea, vomiting).
• Injection site reactions (if subcutaneous).

Key Takeaway:

• Azacitidine is a cornerstone of epigenetic therapy for MDS and AML, especially in patients unfit for intensive chemotherapy.