WQTA | NPM1-mutated AML: Should we abandon Aza/Ven? Fellow: Prof, Aza/Ven outcomes look much worse than I thought in the MD Anderson series. Should we NOT use it? I thought NPM1 AML was VEN-sensitive. Prof: Not so fast. NPM1 does predict VEN sensitivity, but sensitivity is not the same as durable disease control. This retrospective series included only 396 NPM1-mutated patients, with 67 receiving HMA/VEN. Treatment was not randomized. Age, patient selection, co-mutations, FLT3-ITD biology/allelic burden and VEN exposure all matter. Within the HMA/VEN cohort, only age remained independently prognostic after multivariable analysis. PRISM reinforces the larger lesson: NPM1 alone does not determine outcome. The genomic ecosystem matters. VEN duration may matter too. OPTI-AML raises the intriguing possibility that NPM1/IDH2 AML may benefit from longer initial VEN exposure, although this requires validation. And what if our goal is transplant? More patients reaching allo-HCT may be important, but transplant rate alone does not prove one induction strategy is superior. Available retrospective NPM1 data suggest similar post-transplant outcomes after intensive chemotherapy and HMA/VEN. The real question is whether getting more patients to transplant actually produces better overall survival. 🎯 NPM1 predicts VEN sensitivity. It does not guarantee durable disease control. Genotype × VEN exposure × MRD × patient biology × treatment goal. Dr Fun+G #AML #medtwitter