Update on Small Molecule Targeted Therapies for Acute Myeloid Leukemia

Opinion statement The search for effective therapies for the highly heterogenous disease acute myeloid leukemia (AML) has remained elusive. While cytotoxic therapies can induce complete remission and even, at times, long-term survival, this approach is associated with significant toxic effects to visceral organs and worsening of immune dysfunction and marrow suppression leading to death. Sophisticated molecular studies have revealed defects within the AML cell that can be exploited by utilizing small molecule agents to target these defects, often dubbed “target therapy.” Several medications have already established new standards of care for many patients with AML, including FDA-approved agents that inhibitor IDH1, IDH2, FLT3, and BCL-2. Emerging small molecules hold additional to add to the armamentarium of AML treatment options including MCL-1 inhibitors, TP53 inhibitors, menin inhibitors, and E-selectin antagonists. Moreover, the increasing options also mean that future combinations of these agents need to be explored, including with cytotoxic drugs and other newer emerging strategies such as immunotherapies for AML. Recent investigations continue to show that overcoming many of the challenges of treating AML finally is on the horizon.