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

• In Non–Low-Risk AML, the addition of venetoclax to FLAI induction chemotherapy gives high rate of complete remission and limited toxicities

• In V-FLAI combination, venetoclax 600 mg was not markedly superior to venetoclax 400 mg in term of remission rate or survival

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