Mechanisms of action of immunomodulatory drugs in plasma cell myeloma

Abstract

Plasma cell myeloma is a multi-stage disease that is characterized by monoclonal proliferation of plasma cells. The last decades brought a major breakthrough in the treatment of multiple myeloma, concerning the new medicine and the therapeutic schema which vitally lengthen the lifespan of patients suffering from this incurable disease. Thalidomide has been the first within the group of the immunomodulatory drugs which proved its efficacy in the treatment of patients with myeloma. Identification of its immunomodulatory, anti-inflammatory and antiangiogenic activity resulted in the development of analogues of enhanced activity and lesser toxicity which caused the rapid introduction of lenalidomide into clinical practice. Lenalidomide has turned out to be an immunomodulatory agent able to regulate both the cellular and humoral immune responses by altering cytokine production, it regulates T cell costimulation and augments the NK cell cytotoxicity. It also shows to have anti-angiogenic properties. The latest studies have demonstrated that another immunomodulatory drug — pomalidomide — has a potent anti-myeloma activity in vitro and in vivo, acting both directly on myeloma cells and on the cells in the bone marrow microenvironment. The aforementioned data of the literature suggest high efficacy of thalidomide, lenalidomide and pomalidomide in the treatment of myeloma.
Hematologia 2011; 2, 2: 105–115