Key Takeaways
- Azacitidine plus venetoclax (aza-ven) significantly improved event-free survival compared with intensive chemotherapy in fit AML patients.
- Overall and composite remission rates were higher with aza-ven, despite similar complete remission rates.
- Patients receiving aza-ven experienced fewer hospital days, less ICU use and better quality-of-life scores.
- More patients were able to proceed to allogeneic transplant after aza-ven than after intensive chemotherapy.
- Toxicity rates were comparable, with numerically fewer early deaths in the aza-ven arm.
- Findings suggest aza-ven may represent a viable frontline alternative to intensive chemotherapy in selected patients.
The PARADIGM study (Abstract 6) was presented during the Plenary Scientific session at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition. The randomized phase II trial showed that azacitidine plus venetoclax (aza-ven) demonstrated superior event-free survival (EFS), higher response rates, and better patient-reported outcomes compared with intensive chemotherapy (IC) in fit, newly-diagnosed patients with acute myeloid leukemia (AML). The findings challenge IC as the default frontline therapy even in younger, IC-eligible patients.
The study was an open-label, multicentre, phase II randomized trial enrolling 172 IC-eligible adults with newly diagnosed AML across nine US centeres. Patients were randomized 1:1 to receive either aza-ven or conventional intensive chemotherapy (7+3 or CPX-351). Key exclusions included core binding factor AML, FLT3 mutations, and NPM1 mutations in patients under 60 years. Patients could proceed to allogeneic hematopoietic cell transplant (HCT) after response.
The primary endpoint was event-free survival (EFS), defined as progression, persistent disease requiring therapy change, relapse, hospice or death. Secondary endpoints included response rates, overall survival, toxicity, measurable residual disease, hospitalization metrics and quality of life. Patients were stratified by age and IC regimen. EFS was assessed using Kaplan–Meier and Cox proportional hazards models.
As of 25 July 2025, all 172 patients had been enrolled (86 per arm). Median age was 64–65 years, with balanced baseline characteristics and molecular risk profiles across groups.
- Overall response rate (OR): 88% with aza-ven vs 62% with IC (P<0.001)
- Composite complete remission (CCR): 81% vs 55% (P<0.001)
- Complete remission (CR): 59% vs 50% (P=0.066)
- 1-year EFS: 53% (aza-ven) vs 39% (IC)
- EFS hazard ratio: 0.61 (P=0.017)
- Progression to HCT: 61% (aza-ven) vs 40% (IC) (P=0.009)
Median follow-up was 16 months. EFS benefit remained significant after adjustment for age. Grade 3–4 toxicities were similar between arms. Rates of grade 3–4 lung infections and sepsis were 12% and 7% with aza-ven versus 15% and 11% with IC, respectively. Thirty- and 60-day mortality were 0% with aza-ven versus 3.5% and 4.7% with IC.
Patients receiving aza-ven had significantly better early quality-of-life outcomes, including improved symptom burden (P=0.019) and depression scores (P=0.007). They required fewer ICU admissions (0% vs 9.8%), fewer inpatient days during initial hospitalization (15 vs 36), and fewer total hospital days in the first six months (41 vs 58; all P<0.001).
The trial met its primary endpoint, demonstrating that azacitidine plus venetoclax provides superior event-free survival and higher response rates than intensive chemotherapy in fit AML patients. The regimen was associated with better tolerability, fewer hospitalizations, improved quality of life, and a higher likelihood of proceeding to transplant. These results suggest aza-ven may represent a viable frontline alternative to intensive chemotherapy in selected, fit patients, with overall survival data still maturing.
References
- Fathi A, Perl A, Fell G. Results from paradigm – a phase 2 randomized multi-center study comparing azacitidine and venetoclax to conventional induction chemotherapy for newly diagnosed fit adults with acute myeloid leukemia (Abstract 6). Presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6-9, 2025.
Related content
- FDA grants orphan drug status to zavabresib in myelofibrosis
- ASH25 highlights: Translating evidence into haematology practice
- A year in review: Expert voices on the developments that defined 2025
-
This content has been developed independently by Touch Medical Media for touchHAEMATOLOGY. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Cite: PARADIGM challenges role of intensive chemotherapy in newly diagnosed AML. touchHAEMATOLOGY. 28th January 2026.
Editor: Sophie Nickelson, Editorial Director
Disclosures: This short article was prepared by touchHAEMATOLOGY. The content was developed and edited by human editors. No fees or funding were associated with its publication. touchHAEMATOLOGY utilize AI as an editorial tool (ChatGPT (GPT-4o) [Large language model]. https://chat.openai.com/chat).
SIGN UP to touchHAEMATOLOGY!
Join our global community today for access to thousands of peer-reviewed articles, expert insights and learn-on-the-go education across 150+ specialties, plus concise email updates and newsletters so you never miss out.
