Hypomethylating Agents as a Therapy for AML

Acute myeloid leukemia (AML) is predominantly a disease of older adults associated with poor long-term outcomes with available therapies. Used as single agents, hypomethylating agents (HMAs) induce only 15 to 25% complete remissions, but current data suggest that median OS observed after HMAs is comparable to that observed after more intensive therapies. Whether long-term cure may be obtained in some patients treated with HMAs is unknown. Combinations of HMAs to novel agents are now extensively investigated and attractive response rates have been reported when combining HMAs to different drug classes. The absence of reliable predictive biomarkers of efficacy of HMAs in AML and the uncertainties regarding their most relevant mechanisms of action hinder the rational design of the combinations to be tested in priority, usually in untreated older AML patients.