Therapeutic choices after hypomethylating agent resistance for myelodysplastic syndromes

Therapeutic choices after hypomethylating agent resistance for myelodysplastic syndromes Purpose of reviewHypomethylating agents (HMAs) are the standard of care for patients with myelodysplastic syndromes (MDS). Although these agents induce responses in up to 40% of patients, most patients ultimately experience loss of response. The purpose of this review is to provide an overview of the different therapies under development for MDS after HMA therapy.Recent findingsRecent advances in the understanding of MDS pathogenesis have led to the development of new potential therapies after HMA failure. Newer HMAs, less susceptible to in-vivo deamination, such as guadecitabine or ASTX727 have shown activity. Alterations of immune checkpoints in MDS have led to multiple clinical trials evaluating the activity of monoclonal antibodies targeting these proteins (pembrolizumab, nivolumab, ipilimumab). Different combinations and new formulations of cytotoxic agents, such as clofarabine or CPX-351, are newer options for specific subsets of patients. Finally, targeted agents inhibiting multiple kinases (rigosertib), BCL2 (venetoclax) or mutant IDH1 (ivosidenib), IDH2 (enasidenib), FLT3 (sorafenib, midostaurin) or spliceosome components (H3B-8800) are other novel options.SummaryDespite the poor prognosis associated with HMA failure, clinical trials, new cytotoxic agents and allogeneic stem-cell transplantation, can offer therapeutic opportunities for these patients for whom there is no standard of care. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Current Opinion in Hematology Wolters Kluwer Health

Therapeutic choices after hypomethylating agent resistance for myelodysplastic syndromes

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Publisher
Wolters Kluwer
Copyright
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
ISSN
1065-6251
eISSN
1531-7048
D.O.I.
10.1097/MOH.0000000000000400
Publisher site
See Article on Publisher Site

Abstract

Purpose of reviewHypomethylating agents (HMAs) are the standard of care for patients with myelodysplastic syndromes (MDS). Although these agents induce responses in up to 40% of patients, most patients ultimately experience loss of response. The purpose of this review is to provide an overview of the different therapies under development for MDS after HMA therapy.Recent findingsRecent advances in the understanding of MDS pathogenesis have led to the development of new potential therapies after HMA failure. Newer HMAs, less susceptible to in-vivo deamination, such as guadecitabine or ASTX727 have shown activity. Alterations of immune checkpoints in MDS have led to multiple clinical trials evaluating the activity of monoclonal antibodies targeting these proteins (pembrolizumab, nivolumab, ipilimumab). Different combinations and new formulations of cytotoxic agents, such as clofarabine or CPX-351, are newer options for specific subsets of patients. Finally, targeted agents inhibiting multiple kinases (rigosertib), BCL2 (venetoclax) or mutant IDH1 (ivosidenib), IDH2 (enasidenib), FLT3 (sorafenib, midostaurin) or spliceosome components (H3B-8800) are other novel options.SummaryDespite the poor prognosis associated with HMA failure, clinical trials, new cytotoxic agents and allogeneic stem-cell transplantation, can offer therapeutic opportunities for these patients for whom there is no standard of care.

Journal

Current Opinion in HematologyWolters Kluwer Health

Published: Mar 1, 2018

References

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