Role of Lenalidomide in the Treatment of Myelodysplastic Syndromes

Lenalidomide is characterized as an immunomodulatory drug (IMiD), a second-generation drug in this proprietary drug class with greater potency and a toxicity profile that is distinct from the lead compound, thalidomide. Clinical trials exploring its role in treating patients with myelodysplastic syndrome (MDS) revealed unique karyotype-specific activity in patients with interstitial deletion of the long arm of chromosome 5 (del(5q)). This observation ultimately led the US Food and Drug Administration (FDA) to approve lenalidomide for the treatment of lower risk transfusion-dependent patients with del(5q) MDS. Herein we review the results of four clinical trials conducted with lenalidomide in lower risk MDS, summarizing the clinical efficacy and safety of the drug. We discuss the use of lenalidomide in non-del(5q) patients and efforts to optimize its activity, in addition to investigations exploring the role of lenalidomide in higher risk MDS and acute myeloid leukemia (AML). Finally, we highlight the current understanding of its mechanism of action, discussing the emerging insight into the underlying biology of del(5q) MDS and its linkage to potential targets of lenalidomide.