title: Immunomodulatory drugs in multiple myeloma.
abstract: Immunomodulatory drugs (IMiDs) are thalidomide analogues that retain the direct anticancer cytotoxic and immunological activity of their parent compound, but with a different toxicity profile. In vitro studies show that IMiDs have a more potent antitumour effect than thalidomide on multiple myeloma (MM) cell lines. This activity is mediated by multiple mechanisms: direct antiproliferative effect; inhibition of angiogenesis due to reduced IL-6 and vascular endothelial growth factor secretion; inhibition of cytokines production, especially TNF-alpha; and stimulation of T-cell activity. Two IMiDs, CC-5013 and CC-4047, have been tested in clinical trials in MM patients with progressive or refractory disease, and one trial is ongoing in newly diagnosed MM patients. Observed toxicities include thrombocytopoenia, neutropoenia and cardiovascular events, but no significant neurotoxicity has been reported. Partial responses (> or = 50% reduction in M-protein) ranged from 20 to 71% in different studies depending on the pretreatment status of the patients. The combination of IMiDs with dexamethasone may be beneficial.
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. SandersToniJ@uams.edu
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zangari
authors.forename: Francesca
authors.initials: F
authors.lastname: Elice
authors.forename: Guido
authors.initials: G
authors.lastname: Tricot
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D000077269:Lenalidomide; D009101:Multiple Myeloma / Q000188:drug therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D007155:Immunologic Factors; D013792:Thalidomide; D000077269:Lenalidomide