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

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.