Immunomodulatory drugs in multiple myeloma: From molecular mechanisms of action to clinical practice

Roberto Castelli, Antonino Cannavò, Fabio Conforti, Giovanni Grava, Agostino Cortelezzi

Research output: Contribution to journalArticlepeer-review

Abstract

Multiple myeloma (MM) is a clonal disorder of plasma cells that is considered incurable using the currently available treatments. Cytogenetic, molecular and proteonomic techniques have contributed toward a better understanding of the pathophysiology and prognostic factors of this heterogeneous malignancy, whose management has rapidly evolved over the years. The introduction of thalidomide, and the development of safer and more effective thalidomide analogues, represents the major therapeutic advances. Thalidomide, initially used in the treatment of MM because of its angiogenic properties, has considerable therapeutic activity (alone or in combination with other drugs) at all stages of the disease. However, a number of new analogues, such as lenalidomide and pomalidomide, have been developed and are known as "immunomodulatory drugs" (IMIDs). Although they are analogues of thalidomide, they have direct anti-tumor properties, a better tolerability profile and specific activity in both relapsing refractory MM and newly diagnosed disease. The mechanisms of action of IMIDs are still being investigated, but recent studies suggest that, in addition to their anti-angiogenic activity, they have anti-inflammatory and immunomodulatory properties, and directly and indirectly target tumor activity by interfering with various components of the bone marrow (BM) micro-environment. In this paper, we review the pharmacology, mechanisms of action, pre-clinical and clinical efficacy, and the current status of IMIDs in the treatment of MM.

Original languageEnglish
Pages (from-to)740-753
Number of pages14
JournalImmunopharmacology and Immunotoxicology
Volume34
Issue number5
DOIs
Publication statusPublished - Oct 2012

Keywords

  • Immunomodulatory drugs (IMIDs)
  • Immunomodulatory effects
  • Lenalidomide
  • Multiple myeloma
  • Pomalidomide
  • Thalidomide

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pharmacology
  • Toxicology

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