Amonafide: a potential role in treating acute myeloid leukemia

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Amonafide is a novel topoisomerase II (Topo II) inhibitor and DNA intercalator.
• It induces apoptosis by preventing Topo II binding to DNA.
• Amonafide circumvents P-glycoprotein (Pgp)-mediated multi-drug resistance (MDR), a common cause of treatment failure.

Purpose of the Study:

• To evaluate the efficacy and safety of amonafide in patients with secondary acute myeloid leukemia (sAML).
• To assess amonafide's activity in patients with poor prognostic factors, including MDR.
• To investigate the combination therapy of amonafide with cytarabine.

Main Methods:

• In vitro studies assessed Pgp-mediated efflux of amonafide compared to daunorubicin in myeloblasts.
• Clinical efficacy was evaluated in patients with sAML, including those with older age and unfavorable cytogenetics.
• A Phase II trial assessed amonafide in combination with cytarabine.

Main Results:

• Amonafide exhibited significantly less Pgp-mediated efflux than daunorubicin.
• The drug demonstrated efficacy in sAML patients, including those with MDR-associated poor prognostic factors.
• The combination of amonafide and cytarabine achieved a complete remission rate of approximately 40% in sAML patients.
• Efficacy was maintained in poor-risk subsets, including older patients and those with prior myelodysplastic syndrome or therapy.

Conclusions:

• Amonafide plus cytarabine combination therapy shows potential clinical utility for sAML patients.
• This combination may benefit other poor-risk acute myeloid leukemia (AML) subgroups.
• Further trials are ongoing to define amonafide's role in treating poor-risk AML.