Lenalidomide in the treatment of multiple myeloma

Am J Health Syst Pharm. 2007 Sep 1;64(17):1799-807. doi: 10.2146/ajhp070029.

Abstract

Purpose: The pharmacology, clinical use, adverse effects, dosage and administration, and cost of lenalidomide in the treatment of multiple myeloma (MM) are reviewed.

Summary: Lenalidomide is an analogue of thalidomide and has been shown to be more potent than thalidomide in the stimulation of T-cell, interleukin-2, and interferon-gamma production. Both drugs have direct cytotoxic effects on myeloma cells and are capable of inducing apoptosis. They are also capable of reducing angiogenesis through the inhibition of the secretion of vascular endothelial growth factor (VEGF). Inhibition of VEGF leads to alterations in the microvasculature of the bone marrow environment and inhibits myeloma cell growth and proliferation. Unlike thalidomide, lenalidomide has almost no sedative or constipative properties and induces only minimal neurotoxicity; however, there is concern about lenalidomide's teratogenic potential. Phase I, II, and III trials have been carried out with lenalidomide in patients with relapsed or refractory MM, and the drug has shown impressive response rates in relapsed disease. The combination of lenalidomide and dexamethasone has shown superior patient survival. Lenalidomide's efficacy in newly diagnosed MM is currently being studied. Neutropenia and thrombocytopenia were found to be the most common grade 3 or higher toxicities. Rates of these toxicities varied among trials and may have been affected by the setting in which lenalidomide was used (i.e., relapsed or refractory disease versus newly diagnosed MM).

Conclusion: Lenalidomide, a thalidomide analogue, has produced good results when used with dexamethasone in patients with relapsed or refractory MM. Lenalidomide is associated with hematologic toxicities, and participation in a restricted-distribution program is required of prescribers, pharmacies, and patients because of the drug's teratogenic potential.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / economics
  • Antineoplastic Combined Chemotherapy Protocols*
  • Clinical Trials as Topic
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects
  • Drug Approval
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / adverse effects
  • Immunologic Factors / economics
  • Lenalidomide
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / economics
  • Patient Education as Topic
  • Thalidomide / administration & dosage
  • Thalidomide / adverse effects
  • Thalidomide / analogs & derivatives
  • Thalidomide / economics
  • United States

Substances

  • Antineoplastic Agents
  • Immunologic Factors
  • Thalidomide
  • Dexamethasone
  • Lenalidomide