Immunomodulatory drugs in myelodysplastic syndromes

Expert Opin Investig Drugs. 2006 Jul;15(7):805-13. doi: 10.1517/13543784.15.7.805.

Abstract

This review summarises the mechanism of action of immunomodulatory analogues of thalidomide and their use in myelodysplastic syndromes. Thalidomide was found to have a response rate of approximately 20% in these patients. Lenalidomide--which is more potent and less toxic than thalidomide--has been used in three clinical trials and produced the best responses (60 - > 90%) in low- and intermediate-1-risk transfusion-dependent patients with del(5q). The responses are purely erythroid in nature, and are associated with major cytogenetic responses in > 50% of the del(5q) patients. Non-del(5q) low- and intermediate-1-risk transfusion-dependent patients also had a approximately 25% incidence of transfusion independence following therapy with lenalidomide. Median time to response is approximately 4 weeks and 90% of patients respond within 12 weeks. The precise mechanism of action remains unknown but anticytokine, antiangiogenic and immunomodulatory properties are thought to play a role.

Publication types

  • Review

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Apoptosis / drug effects
  • Blood Transfusion
  • Cell Lineage
  • Cells, Cultured / drug effects
  • Chromosome Deletion
  • Chromosomes, Human, Pair 5 / ultrastructure
  • Clinical Trials as Topic
  • Cytokines / physiology
  • Drug Evaluation, Preclinical
  • Drugs, Investigational / therapeutic use*
  • Erythrocyte Transfusion
  • Erythropoiesis / drug effects
  • Female
  • Hematopoietic Stem Cells / drug effects
  • Humans
  • Immunologic Factors / adverse effects
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use*
  • Lenalidomide
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / genetics
  • Myelodysplastic Syndromes / therapy
  • NF-kappa B / antagonists & inhibitors
  • Neutropenia / chemically induced
  • Pilot Projects
  • Thalidomide / adverse effects
  • Thalidomide / analogs & derivatives*
  • Thalidomide / chemistry
  • Thalidomide / pharmacology
  • Thalidomide / therapeutic use
  • Thrombocytopenia / chemically induced
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Angiogenesis Inhibitors
  • Cytokines
  • Drugs, Investigational
  • Immunologic Factors
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Thalidomide
  • pomalidomide
  • Lenalidomide