Molecularly Targeted Therapy in Acute Myeloid Leukemia: Current Treatment Landscape and Mechanisms of Response and Resistance

Simple Summary Molecularly targeted therapy is now a standard treatment option for patients with acute myeloid leukemia and IDH1/2 or FLT3 mutations. This review summarizes the current treatment landscape of IDH and FLT3 inhibitors and emerging targeted therapies for the treatment of AML. Treatment for acute myeloid leukemia (AML) has evolved rapidly over the last decade as improved understanding of cytogenetic and molecular drivers of leukemogenesis refined survival prognostication and enabled development of targeted therapeutics. Molecularly targeted therapies are now approved for the treatment of FLT3 and IDH1/2-mutated AML and additional molecularly and cellularly targeted therapeutics are in development for defined patient subgroups. Alongside these welcome therapeutic advancements, increased understanding of leukemic biology and treatment resistance has resulted in clinical trials investigating combinations of cytotoxic, cellular, and molecularly targeted therapeutics resulting in improved response and survival outcomes in patients with AML. Herein, we comprehensively review the current landscape of IDH and FLT3 inhibitors in clinical practice for the treatment of AML, highlight known resistance mechanisms, and discuss new cellular or molecularly targeted therapies currently under investigation in ongoing early phase clinical trials.

Automated summary

This review summarizes the current landscape of molecularly targeted therapies for patients with acute myeloid leukemia (AML) who have IDH1/2 or FLT3 mutations. The development of targeted therapeutics has improved the treatment options and survival outcomes for AML patients. In addition to approved therapies, ongoing clinical trials are investigating new targeted therapies for specific patient subgroups, in order to overcome treatment resistance.