Targeted next-generation sequencing at the time of AML progression on gilteritinib identified treatment-emergent mutations that activate RAS/MAPK pathway signaling, most commonly in <i>NRAS</i> or <i>KRAS.</i> Less frequently, secondary <i>FLT3</i>-F691L gatekeeper mutations or <i>BCR-ABL1</i> fusions were identified at progression.