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

C. Willekens; R. Rahme; M. Duchmann; V. Vidal; V. Saada; S. Broutin; J. Delahousse; A. Renneville; A. Marceau; E. Clappier; M. Uzunov; J. Rossignol; L. Pascal; L. Simon; J. B. Micol; F. Pasquier; E. Raffoux; C. Preudhomme; C. Quivoron; R. Itzykson; V. Penard-Lacronique; A. Paci; P. Fenaux; E. C. Attar; M. Frattini; T. Braun; L. Ades; S. De Botton

doi:10.1080/10428194.2020.1832661

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

C. Willekens, R. Rahme, M. Duchmann, V. Vidal, V. Saada, S. Broutin, J. Delahousse, A. Renneville, A. Marceau, E. Clappier, M. Uzunov, J. Rossignol, L. Pascal, L. Simon, J. B. Micol, F. Pasquier, E. Raffoux, C. Preudhomme, C. Quivoron, R. ItzyksonV. Penard-Lacronique, A. Paci, P. Fenaux, E. C. Attar, M. Frattini, T. Braun, L. Ades, S. De Botton

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Résumé

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.

langue originale	Anglais
Pages (de - à)	438-445
Nombre de pages	8
journal	Leukemia and Lymphoma
Volume	62
Numéro de publication	2
Les DOIs	https://doi.org/10.1080/10428194.2020.1832661
état	Publié - 1 janv. 2021

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10.1080/10428194.2020.1832661

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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., ... De Botton, S. (2021). Effects of azacitidine in 93 patients with IDH1/2 mutated acute myeloid leukemia/myelodysplastic syndromes: a French retrospective multicenter study. Leukemia and Lymphoma, 62(2), 438-445. https://doi.org/10.1080/10428194.2020.1832661

@article{07a3b72dd22045b89a6a3e376c726dfa,

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

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.",

keywords = "2-hydroxyglutarate, Acute myeloid leukemia, IDH1, IDH2, azacitidine",

author = "C. Willekens and R. Rahme and M. Duchmann and V. Vidal and V. Saada and S. Broutin and J. Delahousse and A. Renneville and A. Marceau and E. Clappier and M. Uzunov and J. Rossignol and L. Pascal and L. Simon and Micol, {J. B.} and F. Pasquier and E. Raffoux and C. Preudhomme and C. Quivoron and R. Itzykson and V. Penard-Lacronique and A. Paci and P. Fenaux and Attar, {E. C.} and M. Frattini and T. Braun and L. Ades and {De Botton}, S.",

note = "Publisher Copyright: {\textcopyright} 2020 Informa UK Limited, trading as Taylor & Francis Group.",

year = "2021",

month = jan,

day = "1",

doi = "10.1080/10428194.2020.1832661",

language = "English",

volume = "62",

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journal = "Leukemia and Lymphoma",

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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, JB, Pasquier, F, Raffoux, E, Preudhomme, C, Quivoron, C, Itzykson, R, Penard-Lacronique, V, Paci, A, Fenaux, P, Attar, EC, Frattini, M, Braun, T, Ades, L & De Botton, S 2021, 'Effects of azacitidine in 93 patients with IDH1/2 mutated acute myeloid leukemia/myelodysplastic syndromes: a French retrospective multicenter study', Leukemia and Lymphoma, VOL. 62, Numéro 2, p. 438-445. https://doi.org/10.1080/10428194.2020.1832661

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T1 - Effects of azacitidine in 93 patients with IDH1/2 mutated acute myeloid leukemia/myelodysplastic syndromes

T2 - a French retrospective multicenter study

AU - Willekens, C.

AU - Rahme, R.

AU - Duchmann, M.

AU - Vidal, V.

AU - Saada, V.

AU - Broutin, S.

AU - Delahousse, J.

AU - Renneville, A.

AU - Marceau, A.

AU - Clappier, E.

AU - Uzunov, M.

AU - Rossignol, J.

AU - Pascal, L.

AU - Simon, L.

AU - Micol, J. B.

AU - Pasquier, F.

AU - Raffoux, E.

AU - Preudhomme, C.

AU - Quivoron, C.

AU - Itzykson, R.

AU - Penard-Lacronique, V.

AU - Paci, A.

AU - Fenaux, P.

AU - Attar, E. C.

AU - Frattini, M.

AU - Braun, T.

AU - Ades, L.

AU - De Botton, S.

PY - 2021/1/1

Y1 - 2021/1/1

N2 - 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.

AB - 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.

KW - 2-hydroxyglutarate

KW - Acute myeloid leukemia

KW - IDH1

KW - IDH2

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U2 - 10.1080/10428194.2020.1832661

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