Ranking Salvage Therapies for Relapsed or Refractory Acute Myeloid Leukemia: Systematic Review & Network Meta-Analysis

Background: Relapsed or refractory acute myeloid leukemia (R/R AML) poses significant therapeutic challenges due to its aggressive nature. With numerous salvage therapies available, clinicians often face uncertainty regarding optimal treatment selection. This network meta-analysis (NMA) aimed to compare the efficacy and safety of available salvage regimens for R/R AML to inform clinical decision-making. Methods: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science was conducted according to PRISMA guidelines to identify randomized controlled trials evaluating salvage therapies in patients with R/R AML. Primary efficacy outcomes included overall survival (OS), event-free survival (EFS), and complete remission rate (CRR); safety outcomes included adverse events (AEs) and treatment-related mortality. A Bayesian NMA was performed using a placebo as the reference comparator, and treatments were ranked using Surface Under the Cumulative Ranking (SUCRA) values. Results: A total of 20 studies (4196 patients) were included. Among the evaluated interventions, gemtuzumab ozogamicin ranked highest for OS (0.85), gilteritinib for EFS (0.81), and apamistamab for CRR (0.85). For safety, cytarabine showed the lowest incidence of AEs (0.71), while enasidenib demonstrated the best profile in reducing mortality (0.87), particularly in patients with IDH2 mutations. Gilteritinib exhibited superior efficacy across multiple endpoints, particularly in patients with FLT3 mutations. Conclusion: This NMA highlights gilteritinib as the most effective and safest salvage therapy for the FLT3-mutated population in R/R AML. Gemtuzumab ozogamicin, apamistamab, and enasidenib also showed favorable outcomes. These findings underscore the importance of individualized therapy selection based on efficacy, safety, and molecular characteristics.