The role of immunomodulatory drugs in multiple myeloma

Abstract

Thalidomide has shown promise in the treatment of newly diagnosed multiple myeloma and relapsed/refractory disease, but side effects such as somnolence, constipation, and neuropathy limit its use. CC-5013, an immunomodulatory drug (IMiD), is more potent than thalidomide. CC-5013 has various immunomodulatory effects, including growth arrest or apoptosis of drug-resistant myeloma cell lines and inhibition of binding of myeloma cells to bone marrow stromal cells. Clinically, 17 of 24 patients (71%) with relapsed/refractory disease experienced a reduction of paraprotein of ≥25% following treatment with CC-5013, including 11 who had a history of treatment with thalidomide. Another two experienced stable disease. Median time to best response was 2 months (range, 1 to 11) and median duration was 6 months (range, 2 to 18). Grade 3 thrombocytopenia was seen in 20% of patients; grade 3 neutropenia was seen in 60%; and grade 4 neutropenia was seen in 16%. CC-5013 use was not associated with somnolence, constipation, or neuropathy. This article reviews thalidomide in multiple myeloma, the effects of thalidomide analogues IMiDs, and the preclinical and clinical data on CC-5013 in relapsed/refractory multiple myeloma.