New frontline therapy for AML?

Chemotherapy has been the standard first-line option for fit adults with acute myeloid leukaemia (AML) for decades. However, a different therapy has shown promising results in the frontline AML setting, potentially replacing chemotherapy as the initial treatment option for this population.

The phase 2 PARADIGM trial (NCT04801797) randomised 172 functionally fit participants with newly diagnosed FMS-like tyrosine kinase 3 (FLT3)-wild type AML 1:1 to induction chemotherapy (7+3 or CPX-351) or to azacitidine plus venetoclax. The primary endpoint was event-free survival (EFS), and Prof. Amir Fathi (Harvard Medical School, MA, USA) presented the primary results [1].

After a median follow-up of 21.9 months, the median EFS was 14.6 months for participants receiving azacitidine plus venetoclax and 6.2 months for participants receiving chemotherapy (HR 0.57; P=0.0021). Prof. Fathi noted that a higher number of participants in the azacitidine–venetoclax arm proceeded to transplant (n=52 vs n=34; P=0.009). “Although transplant had a significant protective effect on EFS, the azacitidine–venetoclax regimen still resulted in improved EFS outcomes after adjusting for transplant (HR 0.67; P=0.030).”

The median overall survival was 21.5 months in the experimental arm and 18.6 months in the control arm (P=0.19). “Participants with relapse or refractoriness frequently crossed over to the therapy they did not receive in the first line, potentially explaining the lack of effect on overall survival,” argued Prof. Fathi.

Grade ≥3 infections (20.8% vs 15.1%) and bleeding events (6.3% vs 1.3%) were more common in the chemotherapy arm. Also, the 60-day mortality rate was 4.7% in the chemotherapy arm versus 0% in the azacitidine–venetoclax arm.

“Azacitidine–venetoclax improved EFS compared with conventional induction chemotherapy in this population of patients with FLT3-wild type AML,” concluded Prof. Fathi. “Moreover, the experimental therapy was associated with less early mortality, improved quality-of-life outcomes, and less time spent in the hospital.”

1. Fathi AT, et al. Results from PARADIGM: a phase 2 randomized multi-center study comparing azacitidine and venetoclax to conventional induction chemotherapy for newly diagnosed fit adults with AML. Abstract 6, American Society of Hematology (ASH) annual meeting 2025, 6–9 December, Orlando, Florida, USA.

 Copyright ©2025 Medicom Medical Publishers



Posted on 22 December 202522 December 2025