A phase 1b/2 study found that adding the IDH1 inhibitor ivosidenib to the standard combination of venetoclax and azacitidine produced deep and durable responses in patients with newly diagnosed IDH1-mutated acute myeloid leukemia (AML) who were not candidates for intensive chemotherapy.
The trial enrolled 40 patients with a median age of 72 years. Patients received ivosidenib, venetoclax, and azacitidine as frontline treatment. After a median follow-up of 35 months, the overall response rate was 95%, and 93% of patients achieved a complete response or a similar high-quality remission. Responses occurred quickly, typically within two treatment cycles.
Among evaluable responders, 91% became minimal residual disease (MRD) negative, indicating very low levels of remaining leukemia. Median overall survival and duration of response had not yet been reached, while the 3-year overall survival rate was 79%.
The treatment was generally well tolerated, with only 5% of patients stopping therapy because of side effects. Researchers are now evaluating the regimen in the randomized phase 3 EVOLVE-1 trial to determine whether it can outperform current standard doublet therapies.