Isocitrate Dehydrogenase (IDH) 1 and 2 Mutations Predicts Better Outcome in Patients with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation: a study of the ALWP of the EBMT

Razan Mohty,Abdul-Hamid Bazarbachi, Myriam Labopin,Jordi Esteve, Nicolaus Kröger, Jan CORNELISSEN,Didier Blaise, Gerard Socie, Sébastien Maury,Arnold Ganser,Tobias Gedde-Dahl,Peter von dem Borne,Jean Bourhis,Claude-Eric BULABOIS, Ibrahim Yakoub-Agha,Caroline Pabst,Stéphanie Nguyen, Patrice Chevallier, Anne Huynh,Ali Bazarbachi,Arnon Nagler, Fabio Ciceri, Mohamad Mohty


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Abstract Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) mutations have uncertain prognostic implications in AML. We investigate the impact IDH1 and IDH2 mutations 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 IDH1 mutation (mIDH1), and 26.27% (n = 398) IDH2 mutation (mIDH2) and 57.82% (n = 876) had no-IDH mutation. NPM1 was frequently encountered with IDH1 mutation (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 mIDH1 and mIDH2 compared 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 mIDH1 group, overall survival (OS) was improved compared to no-IDH (HR = 0.68 (95%CI 0.48–0.94), p = 0.021), whereas mIDH2 was 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 NPM1 wild type, only IDH2 was associated with improved outcomes. In conclusion, our data suggest that IDH1 and IDH2 mutations are associated with improved outcomes in patients with AML undergoing allo-HCT in CR1.
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