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Outlook and Management of Patients with Myelodysplastic Syndromes Failed by Hypomethylating Agents

  • Myelodysplastic Syndromes (D Steensma, Section Editor)
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Abstract

The DNA hypomethylating agents (HMAs) azacitidine and decitabine are currently the most frequently administered disease-modifying therapies for patients with higher-risk myelodysplastic syndromes (MDS). However, azacitidine and decitabine are not curative, the median response duration is 11–15 months, and only 10–20 % of patients experience complete hematologic and cytogenetic response. Moreover, once an HMA fails the patient, the prognosis is poor, with a median survival of less than 6 months unless the patient undergoes hematopoietic stem cell transplantation (HSCT). Recent insights into the genetic basis of MDS have enhanced biological understanding and prognostication accuracy, but these developments have not yet led to regulatory approval of new therapies. While there are multiple potential approaches to patients with MDS for whom HMAs have failed, including supportive care alone, cytotoxic therapy, lenalidomide, histone deacetylase inhibitors, and HSCT, favorable responses to these approaches are limited and new therapies are greatly needed. Here, we review clinical and biological data about the population of patients failed by HMAs, evaluate currently available approaches to patients in this clinical situation, and discuss prospects for development of novel active agents.

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Conflict of Interest

Daniel A. Roberts declares no potential conflicts of interest.

David P. Steensma is a section editor for Current Hematologic Malignancy Reports. He has served as a consultant to Onconova, Novartis, and MEI Pharma.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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  1. Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Daniel A. Roberts

  2. Division of Hematological Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, 02215, MA, USA

    David P. Steensma

  3. Harvard Medical School, Boston, MA, 02215, USA

    David P. Steensma

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  1. Daniel A. Roberts
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Correspondence to David P. Steensma.

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This article is part of the Topical Collection on Myelodysplastic Syndromes

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Roberts, D.A., Steensma, D.P. Outlook and Management of Patients with Myelodysplastic Syndromes Failed by Hypomethylating Agents. Curr Hematol Malig Rep 10, 318–328 (2015). https://doi.org/10.1007/s11899-015-0273-2

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