Immunomodulatory drugs in myelodysplastic syndromes.
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.
Galili
Naomi
N
The Radhey Khanna MDS Center, University of Massachusetts Medical Centre, Division of Hematology, Department of Medicine, 364 Plantation Street, LRB 208, Worcester, MA 01605, USA. naomi.galili@umassmed.edu
Raza
Azra
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001803:Blood Transfusion; D019070:Cell Lineage; D002478:Cells, Cultured / Q000187:drug effects; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000648:ultrastructure; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D015507:Drugs, Investigational / Q000627:therapeutic use*; D017707:Erythrocyte Transfusion; D004920:Erythropoiesis / Q000187:drug effects; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics / Q000628:therapy; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009503:Neutropenia / Q000139:chemically induced; D010865:Pilot Projects; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000139:chemically induced; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology
D020533:Angiogenesis Inhibitors; D016207:Cytokines; D015507:Drugs, Investigational; D007155:Immunologic Factors; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; C467566:pomalidomide; D000077269:Lenalidomide