Did PARADIGM Trial Set a New Standard in High-Risk AML?

In this Chief Insights video, John M. Burke, MD, of Rocky Mountain Cancer Centers highlighted key findings from the PARADIGM trial, a plenary session abstract presented at the ASH 2025 annual meeting. The phase 2 randomized study investigated whether the targeted combination of azacitidine and venetoclax could replace intensive chemotherapy in younger, fit patients with high risk acute myeloid leukemia. Traditionally, intensive chemotherapy with a seven plus three regimen has been the standard for this population for decades, while the azacitidine and venetoclax combination has been reserved for unfit patients.

The trial enrolled 172 adults with newly diagnosed AML, excluding those with favorable risk features or FLT3 mutations. Results favored the azacitidine and venetoclax arm, which demonstrated superior median event free survival at 14.6 months compared to 6.2 months in the control arm. Response rates were higher at 88% versus 62%, and more patients in the targeted therapy arm proceeded to allogeneic stem cell transplant. Notably, the 30 day mortality rate was 0% in the experimental arm versus 3.5% with intensive chemotherapy. While median overall survival was not significantly different, crossover may have influenced this outcome. Quality of life measures also favored the targeted regimen, with fewer hospital days and lower symptom burden.

Dr Burke noted that the study did not compare the targeted combination to intensive chemotherapy containing venetoclax, leaving an unanswered question. He also mentioned additional promising targeted strategies in AML presented at ASH, including menin inhibitors and bispecific antibodies, underscoring the expanding role of targeted therapies in this disease.