TY - JOUR
T1 - Therapeutic choices after hypomethylating agent resistance for myelodysplastic syndromes
AU - Montalban-Bravo, Guillermo
AU - Garcia-Manero, Guillermo
AU - Jabbour, Elias
N1 - Publisher Copyright:
© 2018 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Purpose of review Hypomethylating 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 findings Recent 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. Summary Despite 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.
AB - Purpose of review Hypomethylating 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 findings Recent 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. Summary Despite 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.
KW - azacitidine
KW - decitabine
KW - hypomethylating agents failure
KW - myelodysplastic syndromes
UR - http://www.scopus.com/inward/record.url?scp=85042396563&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042396563&partnerID=8YFLogxK
U2 - 10.1097/MOH.0000000000000400
DO - 10.1097/MOH.0000000000000400
M3 - Review article
C2 - 29266015
AN - SCOPUS:85042396563
SN - 1065-6251
VL - 25
SP - 146
EP - 153
JO - Current opinion in hematology
JF - Current opinion in hematology
IS - 2
ER -