Prognostic value of IDH2R140 and IDH2R172 mutations in patients with acute myeloid leukemia: a systematic review and meta-analysis

Abstract

Abstract Background Whether isocitrate dehydrogenase 2 (IDH2) R140 and R172 gene mutations affect the prognosis of patients with acute myeloid leukemia (AML) is controversial. Here, we performed a meta-analysis to assess their prognostic value. Methods Eligible studies were systematically searched from PubMed, Embase, the Cochrane Library and Chinese databases up to June 1, 2022. We extracted the hazard ratios (HRs) and their 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) to carry out a meta-analysis by a fixed effect model or random effect model according to the heterogeneity between studies. Results A total of 12725 AML patients from 11 studies were included in this meta-analysis, of which 1111 (8.7%) and 305 (2.4%) had IDH2R140 and IDH2R172 mutations, respectively. The results revealed that both IDH2R140 and IDH2R172 mutations had no significant effect on OS (IDH2R140: HR = 0.92, 95% CI: 0.77–1.10, P = 0.365; IDH2R172: HR = 0.91, 95% CI: 0.65–1.28, P = 0.590) or PFS (IDH2R140: HR = 1.02, 95% CI: 0.75–1.40, P = 0.881; IDH2R172: HR = 1.31, 95% CI: 0.78–2.22, P = 0.306) in AML patients. Subgroup analysis of AML patients with IDH2R140 mutation revealed that studies from the USA (HR = 0.60, 95% CI: 0.41–0.89, P = 0.010) and ≤ 50 years old (HR = 0.63, 95% CI: 0.50–0.80, P = 0.000) had longer OS. However, studies from Sweden (HR = 1.94, 95% CI: 1.07–3.53, P = 0.030) had shorter OS. Meanwhile, subgroup analysis of AML patients with IDH2R172 mutation showed that studies from Germany/Austria (HR = 0.76, 95% CI: 0.61–0.94, P = 0.012) and from Sweden (HR = 0.22, 95% CI: 0.07–0.74, P = 0.014) had longer OS, whereas studies from the UK (HR = 1.49, 95% CI: 1.13–1.96, P = 0.005) and studies with nonmultivariate analysis of data type (HR = 1.35, 95% CI: 1.06–1.73, P = 0.014) had shorter OS. In addition, our study also found that patients with IDH2R140 mutation had significantly longer OS (HR = 0.61, 95% CI: 0.39–0.96, P = 0.032) and PFS (HR = 0.31, 95% CI: 0.18–0.52, P = 0.021) than patients with IDH2R172 mutation, despite some degree of heterogeneity. Conclusions This meta-analysis demonstrates that IDH2R140 mutation improves OS in younger AML patients and that the prognostic value of IDH2R172 mutation is significantly heterogeneous. Differences in region and data type have a significant impact on the prognosis of AML patients with IDH2R140 and/or IDH2R172 mutations. Additionally, AML patients with IDH2R140 mutation have a better prognosis than those with IDH2R172 mutations, albeit with some degree of heterogeneity.