Targeted therapies have revolutionized the treatment of cancer; however, under the selective pressures exerted by these therapies, tumor cells with mutations conferring resistance will gradually dominate, leading to relapse. Gilteritinib, a novel FLT3/AXL inhibitor, has emerged as a highly effective drug for the treatment of FLT3-mutated acute myeloid leukemia (AML) in clinical trials. Now, researchers and clinicians are keen to determine what the mechanisms of resistance to this drug will be. Speaking from the American Society of Hematology (ASH) 2017 Annual Meeting and Exposition in Atlanta, GA, Dr Levis discusses an abstract that he presented at the meeting, which analyzed mechanisms of resistance and patterns of relapse in FLT3-mutated AML patients treated with gilteritinib in the CHRYSALIS study (NCT02014558). Mark Levis, MD, PhD, of Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, covers the most common mutation identified and the implications of this.