Anthracycline-Free FLA-VEN with or Without Midostaurin in Newly Diagnosed Intermediate- and Adverse-Risk AML: A Single-Center Retrospective Study

Background: Anthracycline-containing intensive chemotherapy remains a standard frontline approach for medically fit patients with acute myeloid leukemia (AML). We retrospectively evaluated an exploratory anthracycline-sparing regimen combining fludarabine, cytarabine, and venetoclax (FLA-VEN), with midostaurin added in FLT3-mutated cases, in selected patients with intermediate- or adverse-risk AML. Methods: This retrospective single-center study included 24 consecutive adults with newly diagnosed intermediate- or adverse-risk AML treated between March 2024 and March 2026. Patients with favorable-risk AML were excluded. The primary endpoints were complete remission (CR) and safety. Secondary endpoints included hematologic recovery, allogeneic hematopoietic stem cell transplantation (allo-HSCT) rate, relapse incidence, transplant-related mortality (TRM), and overall survival (OS). Results: The median age was 49 years (range, 22–64), and 16.7% of patients were aged ≥60 years. FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutations were present in 8 patients (33.3%). Following one induction cycle, 21 of 24 patients (87.5%) achieved CR. Among FLT3-ITD-mutated patients, 7 of 8 (87.5%) achieved CR, and FLT3-ITD became undetectable by the available polymerase chain reaction (PCR) fragment assay in all seven responders before transplantation. The 60-day mortality rate was 0/24 (0%). Median neutrophil and platelet recovery times were 17 and 21 days, respectively. Twenty-one patients (87.5%) underwent allo-HSCT in first remission. With a database cutoff of 30 August 2026, Kaplan–Meier estimated OS was 83.3% (95% CI, 61.5–93.4%) at 12 months. The longer-term 24-month OS estimate was 54.4% (95% CI, 25.5–76.3%); however, this estimate was imprecise because only five patients remained at risk at 24 months. Median OS was not reached. Conclusions: In this small exploratory cohort, anthracycline-free and G-CSF-free FLA-VEN, with or without midostaurin, was associated with high remission rates, no early mortality, and frequent bridging to allo-HSCT. These findings support prospective controlled evaluation of this anthracycline-sparing strategy.