An updated systematic review, meta-analysis and network meta-analysis of the clinical benefit and safety of gemtuzumab ozogamicin in treating acute myeloid leukemia in various subgroups
Summary. Previous studies have shown the overall results of gemtuzumab ozogamicin (GO), an anti-CD33 humanized antibody, for the treatment of acute myeloid leukemia (AML). The aim of this updated systematic review, meta-analysis and network meta-analysis was to comprehensively explore the clinical benefits and safety of GO in various subtypes of AML. Materials and methods. PubMed, Embase, Cochrane, and Chinese databases were filtered for randomized controlled trials (RCTs) and retrospective cohort studies to examine the clinical efficacy and safety of GO in AML. Random-effects model was used to calculate pooled effect sizes and 95% confidence intervals. Relative risk (RR) was used to assess complete remission (CR), early death, and drug toxicity. The hazard ratio (HR) was used to analyze survival rates. Results. 15 RCTs and 15 retrospective cohort studies were analyzed (the total number of individuals who received GO was 4768, and the number of participants in the control group was 6466, respectively). The use of GO was characterized by a tendency to improve the CR (HR 0.95; p=0.084), and a significant improvement in survival rates (overall survival (OS) was 0.86 (p=0.003); event-free survival (EFS) was 0.86 (p=0.015), relapse-free survival – 0.83 (p=0.001), and cumulative incidence of relapse – 0.82 (p <0.001) respectively). GO benefits of CR and survival were evident in favorable- and intermediate-risk karyotypes (p ≤0.023). GO advantages were also associated with nucleophosmin 1 mutations (p ≤0.04), wild-type FMS-like tyrosine kinase 3 internal tandem duplication gene (p ≤0.03), age of <70 years (p <0.05), de novo AML (p ≤0.017) and CD33(+) antigen (p ≤0.021). The addition of GO to induction therapy (p ≤0.011) and the use of this drug in a lower dose (<6 mg/m2) (p ≤0.03) also improved patient survival. However, the use of a higher dose of GO (≥6 mg/m2) was associated with an increased risk of risk of early death (RR 2.01; p=0.005), hepatic-related adverse effects (RR 1.29; p=0.02), and a tendency of higher risk for hepatic veno-occlusive disease or sinusoidal obstruction syndrome (RR 1.56; p=0.072). Conclusions. The obtained results indicate the therapeutic advantages and safety of the use of GO in AML, especially in some subtypes of the disease.
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