Immunomodulatory therapy for myelodysplastic syndromes

Thalidomide and lenalidomide belong to the proprietary group of immunomodulatory drugs (IMiDs) that display broad biologic and pharmacologic properties. Encouraging results of clinical studies that evaluated the efficacy of thalidomide in patients with myelodysplastic syndromes (MDSs) led to the investigation of its structural analogue, lenalidomide, in patients with lower-risk MDS. The cumulative results of studies that tested lenalidomide in patients with interstitial deletion of chromosome 5q, ie, del(5q), showed a high frequency of both erythroid and cytogenetic responses (approximately 75% of patients), which led to US Food and Drug Administration approval of this agent for this cytogenetically defined MDS subset. A multicenter phase III study (MDS-002) that investigated the frequency of transfusion response in lower-risk non-del(5q) MDS patients showed that lenalidomide had significant erythropoietic activity, albeit less robust in lower-risk MDS without del(5q). These studies established lenalidomide as an active erythropoietic-remitting agent with novel cytogenetic-remitting activity in lower-risk MDS patients who would not otherwise benefit from therapy with erythropoietic growth factors. The National Comprehensive Cancer Network Clinical Practice Guidelines recently added lenalidomide to the therapeutic algorithm for MDS as front-line therapy for lower-risk MDS patients with del(5q) and transfusion-dependent anemia.