- Design
- Multicentre, randomised, phase 2 trial
- Population
- 172 induction-eligible adults with untreated AML, median age 64, 72% adverse risk
- Primary outcome
- Event-free survival
- Effect
- 14.5 vs 6.2 months, HR 0.57 (95% CI 0.39–0.84); grade ≥3 infection 28% vs 41%
PARADIGM, a phase 2 trial, randomised 172 previously untreated adults with AML who were fit for intensive induction to azacitidine plus venetoclax or induction chemotherapy. Patients with core-binding factor fusions or FLT3 mutations were excluded, as were those under 60 with NPM1 mutations. Median age was 64, and 72% had adverse-risk disease by ELN 2022. It was published in September 2026.
Median event-free survival was 14.5 months with azacitidine-venetoclax and 6.2 months with induction (HR 0.57). Grade 3 or higher infections were 28% against 41%, and serious bleeding 2% against 12%.
For a fit patient with adverse-risk AML, the lower-intensity regimen now has randomised evidence of better event-free survival and fewer serious complications. In India, where intensive induction carries high infection-related mortality and long admissions, this is especially relevant. But this is a phase 2 trial, overall survival and transplant outcomes are not reported in the abstract, and favourable-risk subgroups were excluded. It should inform discussion, not replace induction for everyone.
- Establish ELN risk, FLT3, NPM1 and core-binding factor status before choosing induction
- Discuss azacitidine-venetoclax as an option for fit patients with adverse-risk disease
- Keep intensive induction for favourable-risk and FLT3- or NPM1-mutated disease, which were excluded
- Plan transplant referral early, whichever regimen is chosen
- Watch for prolonged cytopenias with venetoclax and adjust cycles accordingly
Why it matters
It challenges the assumption that intensive induction is always the best first treatment for a fit patient with AML.
Don't overread it
This is phase 2 evidence on event-free survival; overall survival benefit has not been shown, and several genetic subgroups were excluded.
The statistics, in plain English
HR 0.57 (95% CI 0.39–0.84) means about a 43% lower rate of events, including failure to achieve remission, relapse or death. Event-free survival is not overall survival, and a phase 2 trial of 172 patients can overestimate effects, so a phase 3 confirmation matters.
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