e18518 Background: Standard induction therapy for fit adults with newly diagnosed acute myeloid leukemia (AML) remains daunorubicin–cytarabine (3+7). FLAG-based regimens are increasingly used in high-risk AML, but their comparative efficacy and safety in the frontline setting remain uncertain. We performed a systematic review and meta-analysis to compare FLAG-based induction with standard 3+7 in newly diagnosed AML. Methods: A PRISMA 2020–compliant systematic review was conducted across PubMed, Embase, Cochrane Library, and Web of Science from inception through September 2025. Comparative studies evaluating FLAG or FLAG-IDA versus standard 3+7 induction in adults with newly diagnosed AML were included. Pooled odds ratios (ORs) were calculated using random-effects models. Outcomes included overall response rate (ORR), early mortality (30–60 days), survival outcomes, and treatment-related toxicity. Results: Five retrospective, double-arm cohort studies comprising 534 patients were included (322 FLAG-based; 212 standard 3+7). FLAG-based induction was associated with a significantly higher ORR compared with 3+7 (OR 1.83, 95% CI 1.03–3.22; I² = 34%). There were no significant differences in 30-day (OR 0.56, 95% CI 0.12–2.69) or 60-day mortality (OR 0.79, 95% CI 0.29–2.14). Overall survival outcomes were heterogeneous and could not be pooled; individual studies reported mixed survival results, with benefit observed in selected high-risk cohorts. FLAG-based induction was not associated with increased infectious complications, bacteremia, ICU admission, or prolonged hospitalization compared with standard induction. Patients receiving FLAG were more likely to proceed to consolidation therapy, while rates of allogeneic transplantation were similar between groups. Conclusions: FLAG-based induction therapy improves response rates compared with standard 3+7 in adults with newly diagnosed AML without increasing early mortality or major toxicity. However, survival benefits remain inconsistent and appear influenced by patient selection and post-remission strategies. Prospective randomized trials are required to define the optimal role of FLAG-based induction in contemporary AML treatment algorithms.
Abdulgayoom et al. (Thu,) studied this question.