Symposium Proceedings of the international symposium ACUTE LEUKEMIAS XIX (ISALXIX), Munich March 16–19, 2025

Background: Despite therapeutic advances, the prognosis for intermediate-and high-risk acute myeloid leukemia (AML) remains poor, with an estimated 2-year overall survival (OS) of 30-40% in younger patients.The GIMEMA AML1718 trial investigated the combination of venetoclax with fludarabine, idarubicin, and cytarabine (V-FLAI) as induction therapy to improve outcomes for these patients.Primary endpoint analysis demonstrated a high rate of complete remission (CR) and measurable residual disease (MRD) negativity (79% and 64%, respectively).Here, we present mature data on overall survival (OS) and disease-free survival (DFS).Methods: The GIMEMA AML1718 trial (NCT03455504) is a Phase 1/2 multicenter study that enrolled newly diagnosed adult patients with ELN 2017 intermediate-or high-risk AML.The trial followed a modified Simon's two-stage design.Safety was established in a run-in phase with venetoclax dosages of 400 mg or 600 mg, with no significant difference between the dosages.Part 2 included 67 patients treated with 400 mg V-FLAI.Induction cycles and consolidation treatments were tailored, with allogeneic hematopoietic stem cell transplantation (HSCT) performed when feasible.MRD was centrally assessed in Part 2. A 91-gene panel is under investigation for further characterization of patients.Results: A total of 124 patients were enrolled, with a median age of 55 years (range 18-66), 56% male.At baseline, 54% were classified as intermediate risk, and 46% as high-risk, primarily based on cytogenetics and FLT3/NPM1 status.FLT3 mutations were present in 15.3% of patients, while 14% had secondary AML.After induction, 74 patients (59.6%) proceeded to consolidation, and 71 (57.2%) received HSCT (93% in first CR).With a median follow-up of 22 months, the 1-and 2-year OS were 61% and 48%, respectively, while DFS was 60% and 46%.The survival curves suggest a plateau after 2 years, with 48% of longterm survivals (figure).Safety analysis confirmed low treatmentrelated mortality (4%) and no severe late effects, graft failures, or elevated incidence of graft-versus-host disease.Conclusions: V-FLAI demonstrates durable survival benefits in intermediate-and high-risk AML, with a favorable safety profile.These results suggest that V-FLAI may be a superior induction strategy for fit, non-low-risk AML patients, supporting the need for randomized trials comparing it to standard of care.