Hypomethylating agents for elderly patients with acute myeloid leukemia: a PRISMA systematic review and meta-analysis.

Abstract

Abnormal DNA methylation plays a critical role in acute myeloid leukemia (AML) pathogenesis and hypomethylating agents (HMAs) such as decitabine (5-aza-29-deoxycytidine) and azacitidine (5-azacytidine) are considered efficacious for treating AML. This study aimed to identify if HMAs have therapeutic advantages compared with conventional care regimens (CCR) or placebo in elderly AML patients. We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials from inception to November July 15, 2020. Randomized controlled trials that compared the efficacy and adverse events associated with HMAs, CCR, or placebo were searched. RevMan 5.3 software was used to calculate the hazard ratio (HR) and risk ratio (RR) with a 95% confidence interval (CI). Seven trials with a total of 1966 participants were included. Meta-analyses showed that the overall survival of HMAs was better than that of CCR [HR=0.76, 95% CI (0.69-0.85), (p<0.01)], and the complete remission rate of elderly AML patients was increased by HMAs compared with CCR [RR=1.46, 95%CI (1.08-1.99), p=0.01)]. HMA treatment showed higher incidence of neutropenia [RR=1.30 (95%CI 1.07-1.59, p=0.008)], thrombocytopenia [RR=1.14 (95%CI 1.01-1.59, p=0.04)], and pneumonia [RR=1.37 (95%CI 1.06-1.76, p=0.02)] compared with CCR. Although HMAs cause a higher incidence of adverse events such as neutropenia, thrombocytopenia, and pneumonia, demethylation drugs are well-tolerated and effective for treating AML in the elderly.