Effects of azacitidine in 93 patients with IDH1/2 mutated acute myeloid leukemia/myelodysplastic syndromes: a French retrospective multicenter study. Issue 2 (28th January 2021)

• Record Type: Journal Article
• Authors: Willekens, C.; Rahme, R.; Duchmann, M.; Vidal, V.; Saada, V.; Broutin, S.; Delahousse, J.; Renneville, A.; Marceau, A.; Clappier, E.; Uzunov, M.; Rossignol, J.; Pascal, L.; Simon, L.; Micol, J. B.; Pasquier, F.; Raffoux, E.; Preudhomme, C.; Quivoron, C.; Itzykson, R.; Penard-Lacronique, V.; Paci, A.; Fenaux, P.; Attar, E. C.; Frattini, M.; Braun, T.; Ades, L.; De Botton, S.
• Is Part Of: Leukemia & lymphoma. Volume 62:Issue 2(2021)
• Page Start: 438
• Page End: 445
• Publication Date: 2021-01-28
• Subjects: Acute myeloid leukemia -- azacitidine -- IDH1 -- IDH2 -- 2-hydroxyglutarate; Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.1080/10428194.2020.1832661
• Languages: English
• ISSNs: 1042-8194

Abstract

Abstract: 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.