Phase II PARADIGM trial: Aza + Ven vs induction chemotherapy in adults with untreated AML

Results from the randomized, multicenter, phase II PARADIGM trial (NCT04801797) evaluating azacitidine (Aza) + venetoclax (Ven; n = 86) vs induction chemotherapy (n = 86) in previously untreated adults with acute myeloid leukemia (AML) were published in The New England Journal of Medicine by Fathi et al. The primary endpoint was event-free survival (EFS).

Key data: At a median follow-up of 21.9 months, median EFS was longer with Aza + Ven vs induction chemotherapy (14.5 months vs 6.2 months; hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.39–0.84; p = 0.002). The overall response rate (ORR) was 88% with Aza + Ven vs 62% with induction chemotherapy, and hematopoietic stem cell transplantation (HSCT) transition was achieved in 60% vs 40% of patients, respectively. In the safety population, Grade ≥3 infections occurred in 28% of patients receiving Aza + Ven (n = 86) vs 41% of those receiving induction chemotherapy (n = 82); Grade ≥3 hemorrhage occurred in 2% vs 12% of patients, respectively.

Key learning: In this study, Aza + Ven demonstrated longer EFS than induction chemotherapy in previously untreated adults with AML, as well as encouraging rates of response and progression to HSCT and a favorable safety profile, supporting its use as an upfront treatment option in this population.