Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by the accumulation of immature myeloid precursors with resultant peripheral blood cytopenias. The median age at diagnosis of AML is 67 years and outcomes vary according to clinical and laboratory parameters. However, for most patients, outcomes remain poor with high rates of relapse. According to data from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute, the median overall survival of patients over 66 years with AML is less than 19 months despite intensive therapy. Thus, overall survival is approximately 35% at two years and some subgroups have a less than 5% two-year survival. For the last 43 years, the standard of care has been 3+7 combination chemotherapy, with three days of an anthracycline and seven days of cytarabine.
Recently, there have been dramatic advances in our understanding of AML biology and genetics. This new knowledge is now being translated into better predictive markers and novel therapies in this disease. The new therapies being developed for AML include drugs targeting specific mutated proteins (FLT3-ITD, IDH1/2 mutant) and dysregulated pathways such as signaling, apoptosis and mitochondrial metabolism. Epigenetic dysregulation is a key driver of AML biology and new epigenetic therapies (rearranged MLL, DOT1L, EZH 1/2 and LSD1 inhibitors) are one of many exciting developments for this disease. Novel immune- (anti-CD33, CD123, CD47 or BiTE) and cell-based therapies are also under development.