Mengyi Du1, Fen Zhou2, Runming Jin2, Yu Hu1, Heng Mei3. 1. Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. 2. Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. 3. Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: hmei@hust.edu.cn.
Abstract
PURPOSE: Myelodysplastic syndromes (MDS) are characterized by variable degrees of clinical outcomes. Until now, hypomethylating agents (HMAs) are the only drugs that have been approved by FDA in remedying this complicated prognosis disease, but without satisfactory outcome. So, biomarkers of better clinical outcome are of great significance. Many studies have already reported the potential prognostic value of DNA methylation pathway related gene (TET2/DNMT3 A/IDH) mutations in demethylation therapy patients, with controversial results. Therefore, a meta-analysis was performed to investigate their prognostic impact on HMAs treated MDS. METHODS: Databases, including PubMed, Embase, web of science and the Cochrane Library, were searched for relevant studies published up to 29 May 2018. Overall response rate (ORR) and overall survival (OS) were selected as endpoints. We extracted odds ratio to evaluate the effect of mutations on ORR, and the corresponding hazard ratios and their 95% confidence intervals for OS. RESULTS: A total of 13 cohort studies, covering 1398 patients with MDS treated by HMAs were included in the final meta-analysis. Our results indicated that DNMT3 A mutations had a favorable impact (P = 0.008) and TET2 mutations, which showed no significance (P = 0.06) in all included patients, could imply good efficacy in some subgroups on ORR. However, none advantages of mutations on ORR translated into a benefit in overall survival. CONCLUSIONS: This meta-analysis indicates one favorable factor, DNMT3 A mutations, on ORR in MDS patients with HMAs therapy. The identification of mutations in DNMT3 A can improve clinical efficacy and help make treatment decisions.
PURPOSE:Myelodysplastic syndromes (MDS) are characterized by variable degrees of clinical outcomes. Until now, hypomethylating agents (HMAs) are the only drugs that have been approved by FDA in remedying this complicated prognosis disease, but without satisfactory outcome. So, biomarkers of better clinical outcome are of great significance. Many studies have already reported the potential prognostic value of DNA methylation pathway related gene (TET2/DNMT3 A/IDH) mutations in demethylation therapy patients, with controversial results. Therefore, a meta-analysis was performed to investigate their prognostic impact on HMAs treated MDS. METHODS: Databases, including PubMed, Embase, web of science and the Cochrane Library, were searched for relevant studies published up to 29 May 2018. Overall response rate (ORR) and overall survival (OS) were selected as endpoints. We extracted odds ratio to evaluate the effect of mutations on ORR, and the corresponding hazard ratios and their 95% confidence intervals for OS. RESULTS: A total of 13 cohort studies, covering 1398 patients with MDS treated by HMAs were included in the final meta-analysis. Our results indicated that DNMT3 A mutations had a favorable impact (P = 0.008) and TET2 mutations, which showed no significance (P = 0.06) in all included patients, could imply good efficacy in some subgroups on ORR. However, none advantages of mutations on ORR translated into a benefit in overall survival. CONCLUSIONS: This meta-analysis indicates one favorable factor, DNMT3 A mutations, on ORR in MDSpatients with HMAs therapy. The identification of mutations in DNMT3 A can improve clinical efficacy and help make treatment decisions.
Authors: Abdulla Watad; Mark Kacar; Nicola Luigi Bragazzi; Qiao Zhou; Miriam Jassam; Jan Taylor; Eve Roman; Alexandra Smith; Richard A Jones; Howard Amital; Catherine Cargo; Dennis McGonagle; Sinisa Savic Journal: Front Immunol Date: 2021-02-19 Impact factor: 7.561