International Journal of Hematology

DOI: 10.1007/s12185-019-02651-9 Pages: 161-169

Clinical update on hypomethylating agents

1. INSERM/CNRS UMR 944/7212, Saint-Louis Research Institute, Paris Diderot University

2. Assistance Publique Hôpitaux de Paris, Hematology Laboratory, Hôpital Saint-Louis

3. Assistance Publique Hôpitaux de Paris, Clinical Hematology Department, Hôpital Saint-Louis

Correspondence to:
Raphael Itzykson
Email: raphael.itzykson@aphp.fr

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Abstract

Hypomethylating agents (HMAs), azacitidine and decitabine, are standards of care in higher-risk myelodysplastic syndromes and in acute myeloid leukemia patients ineligible for intensive therapy. Over the last 10 years, research efforts have sought to better understand their mechanism of action, both at the molecular and cellular level. These efforts have yet to robustly identify biomarkers for these agents. The clinical activity of HMAs in myeloid neoplasms has been firmly established now but still remains of limited magnitude. Besides optimized use at different stages of the disease, most of the expected clinical progress with HMAs will come from the development of second-generation compounds orally available and/or with improved pharmacokinetics, and from the search, so far mostly empirical, of HMA-based synergistic drug combinations.

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