Lenalidomide, an IMiD drug (a novel type of immunomodulating drug) was recently 
approved by the US Food and Drug Administration for the treatment of 
transfusion-dependent anemia in patients with myelodysplastic syndromes (MDS) 
and interstitial deletions of chromosome 5q [del(5q)]. This review examines the 
clinical experience from the MDS-001 and MDS-003 clinical trials that led to 
this approval, the results of biological correlates supporting the targets of 
drug action, and the results from a non-del(5q) multicenter study (MDS-002). 
Lenalidomide treatment resulted in both erythroid and cytogenetic responses in 
the majority of patients with del(5q), accompanied by reductions in inflammatory 
cytokine generation and marrow microvessel density and improvement in primitive 
hematopoietic progenitor recovery. Central pathology review showed that 
resolution of cytologic dysplasia was common in patients with del(5q) but was 
infrequent in erythroid-responding patients without the chromosome 5 deletion. 
These findings indicate that lenalidomide promotes erythropoiesis in lower-risk 
MDS, with two apparently distinct mechanisms of action: suppression of the 
ineffective del(5q) clone and promotion of effective erythropoiesis in 
non-del(5q) MDS progenitors. These studies identified lenalidomide as a highly 
active erythropoietic- and cytogenetic-remitting agent in lower-risk MDS 
patients who otherwise would not be expected to benefit from recombinant 
erythropoietin therapy. The most common adverse reactions include dose-dependent 
neutropenia and thrombocytopenia that are more pronounced in patients with 
del(5q) in whom early suppression of the clone is expected.