Role Of TP53 mutations in predicting the clinical efficacy of hypomethylating therapy in patients with myelodysplastic syndrome and related neoplasms: a systematic review and meta-analysis

Abstract Hypomethylating agents (HMAs) are now a major treatment option for myelodysplastic syndrome (MDS) and related neoplasms, but 50% of patients still do not respond and realize poor outcomes. Mutational predictors of treatment efficacy attract continuous attention. Whether TP53 mutations can be used as predictors of HMA effectiveness has caused heated debate. Therefore, we performed a meta-analysis to investigate the predictive value of TP53 mutations to outcomes of HMA therapy in patients with MDS and related neoplasms. We systematically searched PubMed, Embase, the Cochrane Library, and the WanFang databases (published deadline: September 12, 2019). The primary endpoints were overall response rate (ORR) and overall survival (OS). Odds ratio (OR), hazard ratio (HR), and 95% confidence intervals (CI) were pooled to estimate the association between TP53 mutations and the clinical efficacy of HMAs. Four hundred fifteen papers were found, and  22 papers were included in this meta-analysis (N = 2020 participants). The results showed that the presence of TP53 mutation predicted an increased overall response rate with HMA treatment in the subsets that restricted patients in de novo disease, MDS by WHO (World Health Organization) crit eria, or NGS (next-generation sequence) group (P  =  0.005,P  =  0.003,P  =  0.0005, respectively). However, TP53 mutations remained poor factors for OS (P <  0.00001). Collectively, in HMA therapy, TP53 mutations can p...
Source: Clinical and Experimental Medicine - Category: Research Source Type: research