Clinical Benefits and Safety of Gemtuzumab Ozogamicin in Treating Acute Myeloid Leukemia in Various Subgroups: An Updated Systematic Review, Meta-Analysis, and Network Meta-Analysis

Frontiers in Immunology

Li Yu¹  Shujiao He¹  Qingyu Xu² 

[1] Department of Hematology and Oncology, International Cancer Center, Shenzhen Key Laboratory, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University Health Science Center, Shenzhen, China;Department of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany;

关键词: acute myeloid leukemia;    gemtuzumab ozogamicin;    response;    survival;    toxicity;    meta-analysis;   

DOI  :  10.3389/fimmu.2021.683595

来源: DOAJ

【 摘 要 】

BackgroundPrevious trials demonstrated evidence involving the total effects of gemtuzumab ozogamicin (GO), an anti-CD33 humanized antibody, on treating acute myeloid leukemia (AML). In this updated systematic review, meta-analysis, and network meta-analysis (NMA), we aimed to comprehensively explore the clinical benefits and safety of GO in various subtypes of AML.MethodsPubMed, Embase, Cochrane, and Chinese databases were filtered to search randomized controlled trials (RCTs) and retrospective cohort studies that compared clinical efficiency and toxicity of GO with non-GO groups in AML. Random-effects models were used to calculate pooled effect sizes and 95% confidence intervals (CIs). Relative risk (RR) was used for estimating complete remission (CR), early death, and toxicity. Hazard risk (HR) was accomplished to evaluate survival.ResultsFifteen RCTs and 15 retrospective cohort studies were identified (GO: 4,768; Control: 6,466). GO tended to improve CR (RR 0.95, p = 0.084), followed by significantly improved survival (overall survival: HR 0.86, p = 0.003; event-free survival: HR 0.86, p = 0.015; relapse-free survival: HR 0.83, p = 0.001; cumulative incidence of relapse: HR 0.82, p < 0.001). 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(+) (p ≤ 0.021). Both adding GO into induction therapy (p ≤ 0.011) and a lower (<6 mg/m2) dose of GO (p ≤ 0.03) enhanced survival. Prognosis of combined regimens with GO was heterogeneous in both meta-analysis and NMA, with several binding strategies showing improved prognosis. Additionally, GO was related to increased risk of early death at a higher dose (≥6 mg/m2) (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).ConclusionsThese data indicated therapeutic benefits and safety of GO in AML, especially in some subtypes, for which further head-to-head RCTs are warranted.Systematic Review Registration[PROSPERO: https://www.crd.york.ac.uk/prospero/], identifier [CRD42020158540].

【 授权许可】

Unknown