NPM1 and acute myeloid leukemia: Clinical Trajectory of Small-Molecules in Unfit/Relapsed Settings: For drug-resistant scenarios, small-molecule regimens balance efficacy and safety: unfit patients with relapsed AML use venetoclax + hypomethylating agents (HMA) ± FLT3/IDH inhibitors, while post-venetoclax NPM1-mutant AML leverages menin inhibitors to target HOX-driven resistance, with MRD-guided maintenance prolonging remission.