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Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN

Elias Jabbour, Nicholas J. Short, Guillermo Montalban-Bravo, Xuelin Huang, Carlos Bueso-Ramos, Wei Qiao, Hui Yang, Chong Zhao, Tapan Kadia, Gautam Borthakur, Naveen Pemmaraju, Koji Sasaki, Zeev Estrov, Jorge Cortes, Farhad Ravandi, Yesid Alvarado, Rami Komrokji, Mikkael A. Sekeres, David P. Steensma, Amy DeZern, Gail Roboz, Hagop Kantarjian and Guillermo Garcia-Manero

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  • RE: Commentary to: Jabbour et al., Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN. Blood. 2017;130(13):1514-1522.
    • Richard L Momparler, pharmacologist cancer chemotherapy Sevice Hematology-Oncology, Sainte-Justine University Hospital and Dept Pharmacology, Université de Montréal

    One of the key goals of clinical trials on epigenetic agents for the treatment of hematologic malignancies is to determine which agents exhibit the greatest potential to prolong survival. The excellent phase II study by Jabour et al [1] clearly shows that low dose decitabine is more effective than low dose azacitidine for the treatment of low risk MDS. This report confirms our preclinical study in the L1210 leukemia mouse model that decitabine is much more effective that azacitidine (2). The mice were administered a 15 hour i.v. infusion of these epigenetic agents. Decitabine could cure the mice with L1210 leukemia, but not azacitidine, even at much higher doses. This in vivo study was confirmed by an in vitro colony assay using human AML cells, which showed that decitabine was much more potent than azacitidine [3]. Many clinical investigators selected azacitidine over decitabine for their clinical trials on patients with myeloid leukemias (Yun et al) [4]. Perhaps these researchers were not aware of the preclinical data that compared the antileukemic activity of these two inhibitors of DNA methylation or they lacked the confidence that L1210 leukemia mouse model can predict the clinical outcome. The excellent agreement between the clinical results of Jabour et al [1] and the preclinical data [2] indicates that the L1210 leukemia model can be a useful tool to evaluate the clinical potential of new epigenetic agents (Pfilster et al) [5]. In conclusion, the clinical and pre...

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    Conflict of Interest:
    None declared.