Maintenance therapy with hypomethylating agents for patients with acute myeloid leukemia in first remission not eligible for allogeneic hematopoietic cell transplantation: A systematic review and meta-analysis

Abstract

BackgroundOlder patients encompass about 75 % of patients with acute myeloid leukemia (AML). Today therapeutic options to prevent relapse in older patients who managed to achieve complete remission (CR) after intensive chemotherapy are scarce. Recent randomized controlled trials (RCTs) have aimed to reduce the risk of relapse by means of post-CR maintenance therapy. MethodsWe performed a systematic review and meta-analysis of RCTs comparing the efficacy and safety of maintenance with hypomethylating agents (HMA) vs. observation, conventional care or placebo in older patients with AML who are not candidates for allogeneic hematopoietic transplantation (allo−HCT). We searched Cochrane Library, PubMed and conference proceedings up to August 2021. ResultsSix trials were included. Treatment with hypomethylating agents significantly improved overall survival (HR 0.80, 95 % CI 0.70 to 0.91, I2 = 30 %), and disease control (HR 0.80, 95 % CI 0.70 to 0.91, I2 = 0). A significant decrease was seen in both one year mortality (Risk Ratio [RR] 0.61, 95 % CI 0.48 to 0.77, I2 = 0) and mortality at the end of follow-up (RR 0.77, 95 % CI 0.67 to 0.88, I2 = 0). The rate of relapse at 6 months and at one-two years was lower in the HMA arm vs. control (RR, 0.59; 95 % CI, 0.47−0.72; RR, 0.74, I2 = 0; 95 % CI 0.69 – 0.91, I2 = 41 %, respectively). HMA were associated with a statistically non-significant increase in the risk of serious adverse events (RR 3.44, 95 % CI 0.93–12.74, I2 = 80 %). ConclusionsOur meta-analysis shows that in older patients who are not candidates for allo−HCT, maintenance therapy with HMA improves OS and disease control without a statistically significant increase in adverse events.