Isocitrate dehydrogenase (IDH) 1 and 2 mutations predict better outcome in patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation: a study of the ALWP of the EBMT

Isocitrate dehydrogenase 1 and 2 (IDH1and IDH2) mutations have uncertain prognostic implications in AML. We investigate the impact IDH1and IDH2mutations in AML patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) in first complete remission (CR1). In total, 1515 adult patients were included, 15.91% (n= 241) carried IDH1mutation (mIDH1), and 26.27% (n= 398) IDH2mutation (mIDH2) and 57.82% (n= 876) had no-IDH mutation. NPM1was frequently encountered with IDH1mutation (no-IDH group, n= 217, 24.8%, mIDH1, n= 103, 42.7%, mIDH2, n= 111, 27.9%, p< 0.0001). At day 180, the cumulative incidence (CI) of grade II-IV acute graft-versus-host disease (GVHD) was significantly lower in mIDH1and mIDH2compared to no-IDH groups (Hazard ratio [HR] = 0.66 (95% CI 0.47–0.91), p= 0.011; HR = 0.73 (95% CI 0.56–0.96), p= 0.025, respectively). In the mIDH1group, overall survival (OS) was improved compared to no-IDH (HR = 0.68 (95% CI 0.48–0.94), p= 0.021), whereas mIDH2was associated with lower incidence of relapse (HR = 0.49 (95% CI 0.34–0.7), p< 0.001), improved leukemia free survival (LFS) (HR = 0.7 (95% CI 0.55–0.9), p= 0.004) and OS (HR = 0.74 (95% CI 0.56–0.97), p= 0.027). In the subgroup of NPM1wild type, only IDH2was associated with improved outcomes. In conclusion, our data suggest that IDH1and IDH2mutations are associated with improved outcomes in patients with AML undergoing allo-HCT in CR1.