Effects of azacitidine in 93 patients with IDH1/2 mutated acute myeloid leukemia/myelodysplastic syndromes: a French retrospective multicenter study

Leuk Lymphoma. 2021 Feb;62(2):438-445. doi: 10.1080/10428194.2020.1832661. Epub 2020 Oct 12.


Isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) mutations in Myeloid Neoplams (MNs) exhibit DNA hypermethylation via 2-hydroxyglutarate (2HG) over-production. Clinical impact of azacitidine (AZA) remains inconsistent in IDH1/2-mutated MNs and the potential of serum 2HG as a suitable marker of response to AZA is unknown. To address these questions, we retrospectively analyzed 93 MNs patients (78 AML, 11 MDS, 4 CMML) with IDH1/2 mutations treated with AZA. After a median of 5 cycles of AZA, overall response rate was 28% (including 15% complete remission) and median OS was 12.3 months (significantly shorter in AML compared to MDS/CMML patients). In multivariate analysis of AML patients, DNMT3A mutation was associated with shorter OS while IDH1/2 mutation subtypes had no independent impact. No difference was observed in serum 2HG levels upon AZA treatment between responding and refractory patients suggesting that serum 2HG cannot be used as a surrogate marker of AZA response.

Keywords: 2-hydroxyglutarate; Acute myeloid leukemia; IDH1; IDH2; azacitidine.

Publication types

  • Multicenter Study

MeSH terms

  • Azacitidine / therapeutic use
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Mutation
  • Myelodysplastic Syndromes*
  • Retrospective Studies


  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • Azacitidine