ASH 2025 | PARADIGM: Azacitidine + venetoclax vs conventional induction chemotherapy in fit adults with ND AML

Following the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6–9, 2025, Orlando, US, the AML Hub was pleased to speak with Amir Fathi, Massachusetts General Hospital, Boston, US. We asked, How might the phase II PARADIGM trial data impact treatment decisions for newly diagnosed fit adults with acute myeloid leukemia (AML)?  

In this interview, Fathi discussed key findings from the open-label, randomized, phase II PARADIGM trial comparing azacitidine (Aza) + venetoclax (Ven) with conventional induction chemotherapy (IC) in functionally fit patients with newly diagnosed AML (NCT04801797). The trial’s primary endpoint was event-free survival (EFS). 

Key points 

• Patients aged ≥18 years with newly diagnosed AML who were eligible for IC were randomized to receive Aza + Ven (n = 86) or IC (7+3 regimen or liposomal daunorubicin and cytarabine [CPX351]; n = 86).
• Patients meeting the following criteria were excluded from the trial: t(15;17); acute promyelocytic leukemia; core binding factor alterations; FLT3 mutations; NPM1 mutations (in patients aged <60 years); BCR::ABL1 fusion; or mixed phenotype AML.
• At a median follow up of 21.9 months, the median EFS was 14.6 months with Aza + Ven vs 6.15 months with IC (p = 0.0021). The 1-year EFS was 53.4% with Aza + Ven vs 36.0% with IC.
• The median overall survival was 21.5 months vs 18.6 months with Aza + Ven vs IC (p = 0.1873).
• Adverse events were primarily hematologic and occurred at similar rates between arms.
• Compared with Aza + Ven, higher proportions of patients receiving IC experienced Grade ≥3 treatment-emergent infectious (20.8% vs 15.1%; p = 0.04) and bleeding (6.3% vs 1.3%; p = 0.01) adverse events.
• A greater proportion of patients treated with Aza + Ven proceeded to transplant than with IC (p = 0.009).
• The trial’s primary endpoint was met; data demonstrate improved EFS with Aza + Ven vs IC in functionally fit patients with newly diagnosed AML.
  • Furthermore, patient-reported outcomes indicate that Aza + Ven improved quality of life, depression symptoms, and symptom burden, and was associated with reduced healthcare utilization.
  • Together, findings support the use of Aza + Ven in this patient population. 

This educational resource is independently supported by AbbVie. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.