FLAG-Based Versus Standard 7+3 Induction Therapy in Adults with Newly Diagnosed Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis

The standard induction regimen for newly diagnosed acute myeloid leukemia (AML) in eligible patients remains cytarabine-daunorubicin (7+3), although FLAG-based regimens are increasingly used in high-risk disease. We performed a PRISMA 2020-compliant systematic review and meta-analysis comparing FLAG-based induction with standard 7+3 in adults with newly diagnosed AML. Five retrospective cohort studies, including 534 patients, were analyzed. FLAG-based induction was associated with a significantly higher overall response rate than 7+3 (OR 1.83, 95% CI 1.03-3.22), without a significant difference in 30-day mortality (OR 0.56, 95% CI 0.12-2.69) or 60-day mortality (OR 0.79, 95% CI 0.29-2.14). Survival outcomes were heterogeneous and could not be pooled: median OS was similar in one cohort, whereas two studies reported improved OS with FLAG-based induction; DFS/RFS outcomes were inconsistently reported. FLAG-based induction was associated with higher receipt of consolidation therapy, while bridging to allogeneic transplantation did not differ significantly. Cytogenetic and molecular risk data were variably defined and incompletely reported, precluding reliable pooled subgroup analyses. Overall, FLAG-based induction improves response rates without a clear increase in early mortality or selected reported safety outcomes; however, its impact on survival remains uncertain and appears influenced by post-remission strategies. Prospective randomized trials are needed to better define its role in frontline AML therapy.