Safety Run-In and Part 1 of GIMEMA AML1718: Venetoclax Combined with FLAI as Induction Treatment in Non-Low-Risk AML.

The standard induction treatment for acute myeloid leukemia (AML) has limited efficacy for patients with non-low-risk AML. We conducted a multicenter study phase 1b/2, GIMEMA AML1718, to investigate the safety and efficacy of venetoclax (VEN) combined with fludarabine, cytarabine, and idarubicin (V-FLAI) as an induction therapy for non-low-risk AML patients younger than 65 years and at intermediate or high ELN risk. After a safety run-in, patients were randomly allocated to VEN 400 mg or VEN 600 mg cohorts. The primary objectives were safety and composite complete remission (bone marrow blasts <5% with any recovery). We report a predefined interim analysis after 57 patients. Median exposure to VEN during induction was 22 days. Effectiveness and safety were similar between VEN 400 mg and VEN 600 mg cohorts. 60-days mortality was 5.8%. Prolonged aplasia was observed in patients receiving high doses of cytarabine during consolidation. cCR, was achieved in 84% of patients. With a median follow-up of 20.6 months, 1-year overall survival was 71%, 1-year disease free survival was 66.2%, 1-year cumulative incidence of relapse was 24%. V-FLAI is an effective induction therapy for young and fit patients. Fifty-five more patients will be enrolled in part 2; they will receive VEN 400 mg-FLAI as predefined and will be centrally evaluated for measurable residual disease. NCT03455504.