Azacitidine in AML: Key Takeaways From the PARADIGM Study

Jayastu Senapati, MBBS MD Anderson Cancer Center | Uma Borate, MBBS The Ohio State University

January 16, 2026

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Key Points

  • Azacitidine and venetoclax improved outcomes compared with standard induction chemotherapy for fit, young patients with acute myeloid leukemia (AML) in the PARADIGM trial.

  • Minimal residual disease (MRD) may be a valuable treatment endpoint for selecting patients to move to transplant.

  • Azacitidine and ivosidenib appeared to yield more favorable outcomes for IDH1-mutated AML, but azacitidine and venetoclax may allow faster bridging to transplant.

PARADIGM Data at ASH 2025

At the 2025 ASH Annual Meeting (ASH 2025), Jayastu Senapati, MBBS, of MD Anderson Cancer Center, and Uma Borate, MBBS, of The Ohio State University, discussed new data on azacitidine and venetoclax, MRD-guided treatment, and the best therapy for patients with IDH1-mutated AML.

The phase 2 PARADIGM trial compared azacitidine and venetoclax with standard induction chemotherapy in newly diagnosed, fit adults with AML. Treatment with azacitidine and venetoclax significantly improved event-free survival and yielded higher overall response and composite remission rates. In addition, a greater proportion of responders in the azacitidine and venetoclax arm underwent hematopoietic cell transplantation than in the induction chemotherapy arm, according to the ASH 2025 presentation. While the MRD data from PARADIGM were not available at the time of the presentation, the doctors agreed that MRD negativity might be a feasible endpoint to use to bridge to transplant.

Optimal treatment approaches for patients with IDH1-mutated AML were also discussed. Comparing IDH1-mutated populations between the AGILE and VIALE-A trials, azacitidine and ivosidenib may have more favorable toxicity and survival outcomes compared with azacitidine and venetoclax. That said, the AGILE population was ineligible for transplant, and if the goal is to bring a patient to transplant, azacitidine plus venetoclax may be more appropriate because of the more rapid responses, said Dr. Borate.