Who should receive FLAG-IDA-VEN as induction for newly diagnosed AML? The results are impressive: CRc ~95%, MRD negativity ~90%. But perhaps we are asking the wrong question. The question is not whether FLAG-IDA-VEN is active. It clearly is. The question is whether its deeper early response translates into enough durable benefit to justify substantially greater treatment intensity. Once TP53-mutated AML is separated out, the differences among contemporary approaches may be considerably smaller than the early response rates suggest. Importantly, less-intensive VEN-based therapy can still successfully bridge a substantial proportion of patients to allo-HCT. So what are we buying with FLAG-IDA-VEN? More early MRD negativity? Probably. But do we get more sustained MRD negativity? More patients to allo-HCT? Better EFS? Better OS? We don’t know. What we do know is the price of greater intensity: more cytopenias, transfusions, infections, antibiotics/antifungals, hospitalization, supportive care and resource utilization. NCCN lists FLAG-IDA-VEN as a Category 2B option for selected patients, not a preferred induction regimen. And the future may increasingly be VEN + biology rather than VEN + more chemotherapy: FLT3 inhibitors, menin inhibitors, IDH inhibitors and other targeted approaches. A randomized trial could define the true incremental benefit of FLAG-IDA-VEN. It will probably never happen. Until then, the added benefit appears marginal at best, while the added treatment burden is very real. DEEPEST RESPONSE ≠ BEST OUTCOME. SAME BRIDGE TO ALLO. DIFFERENT TREATMENT BURDEN. WHERE IS THE ADDED VALUE? 🧬 In Biology We Trust. #AML #Medtwitter