Immunomodulatory Drugs in Multiple Myeloma

Swati Andhavarapu; Vivek Roy

Disclosures

Expert Rev Hematol. 2013;6(1):69-82. 

In This Article

Abstract and Introduction

Abstract

The introduction of new agents immunomodulatory drugs (IMiDs) and proteasome inhibitors has brought a major shift in therapeutic paradigm in the treatment of newly diagnosed and refractory multiple myeloma (MM). Thalidomide was the first immunomodulatory agent approved for use in myeloma. Although highly active, it is associated with considerable toxicity, particularly in older patients. Lenalidomide, an analog of thalidomide, was developed because of its more potent anti-MM activity and better toxicity profile than the parent compound. Since its introduction in 2004, lenalidomide has established a role in all phases of treatment in MM. The pleiotropic antitumor effects of lenalidomide have translated into clinical efficacy in diseases other than MM. Pomalidomide is a highly potent third-generation IMiD that shares similar pharmacologic properties as thalidomide, with very promising activity in MM and myelofibrosis. This review summarizes the mechanisms of action and clinical activity of IMiDs in MM.

Introduction

Multiple myeloma (MM) is a malignant plasma cell disorder accounting for approximately 10% of all hematologic malignancies. The overall prognosis is driven by tumor biology but other factors such as tumor burden, extent of organ damage and performance status of the patient are important determinants. There has been a significant improvement in survival and quality of life in the last decade with the advent of newer agents, immunomodulatory drugs (IMiDs) and the proteasome inhibitor bortezomib.[1] IMiDs are structural and functional analogs of thalidomide that have potent immunomodulatory properties, antimyeloma activity and better tolerability profile. IMiDs possess antiangiogenic and direct tumoricidal properties and have shown activity against various hematologic malignancies. Lenalidomide, a second-generation IMiD derived from thalidomide, is the only other IMiD available for clinical use. It was approved in December 2005 for red blood cell transfusion-dependent anemia in patients with low- and intermediate-risk myelodysplastic syndrome associated with chromosome 5q31 deletion. It later received US FDA approval in 2006 for MM in combination with dexamethasone in patients who progressed after one previous therapy. Its proven antimyeloma efficacy and relatively minimal toxicity has led to its use in maintenance therapies after autologous stem cell transplantation (ASCT) and following frontline therapy in nontransplant patients.

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