title: Hypomethylating agent combination strategies in myelodysplastic syndromes: hopes and shortcomings.
abstract: The hypomethylating agents (HMA) azacitidine and decitabine are both approved by the FDA for the treatment of myelodysplastic syndromes (MDS). Although heralded as a significant advancement, HMA lead to responses in less than half of patients and for those that respond most will relapse. As such, there is a crucial need to improve frontline therapy approaches. One promising strategy involves combining azacitidine or decitabine with investigational or existing therapies with the goal of achieving synergistic activity and better patient outcomes. The purpose of this paper is to critically review the efficacy and safety of reported HMA-based combination regimens in patients with higher-risk MDS.
authors.affiliation: a Department of Medicine (Hematology) , Yale School of Medicine , New Haven , CT , USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Ball
authors.affiliation: a Department of Medicine (Hematology) , Yale School of Medicine , New Haven , CT , USA.
authors.forename: Amer
authors.initials: A
authors.lastname: Zeidan
authors.affiliation: a Department of Medicine (Hematology) , Yale School of Medicine , New Haven , CT , USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Gore
authors.affiliation: a Department of Medicine (Hematology) , Yale School of Medicine , New Haven , CT , USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Prebet
mesh_terms: D000074322:Antineoplastic Agents, Immunological / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D019175:DNA Methylation / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage; D006801:Humans; D000077269:Lenalidomide; D058990:Molecular Targeted Therapy; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D000074322:Antineoplastic Agents, Immunological; D056572:Histone Deacetylase Inhibitors; D047428:Protein Kinase Inhibitors; D013792:Thalidomide; D000077269:Lenalidomide
keywords: AML; DNA methyltransferase inhibitor; MDS; combination therapy; epigenetic; hypomethylating agent