The IMiDs represent a new proprietary class of thalidomide analogues that 
possess greater potency and less toxicity than the parent compound. As a group, 
these agents share the pharmacologic property of modulating cellular response to 
ligand activation, the precise biologic effect of which is cell lineage and 
stimulant-dependent. Lenalidomide (CC-5013; Revlimid), a second generation IMiD, 
has shown significant erythropoietic activity in patients with lower risk MDS 
that have failed or are not candidates for recombinant erythropoietin treatment. 
Unlike cytokine therapy, lenalidomide suppresses select MDS clones and enhances 
erythropoietin receptor signaling to restore erythropoiesis. Activity is 
greatest in patients with interstitial deletions involving chromosome 5q31.1. A 
multicenter phase II study reported a 76 % overall transfusion response rate in 
transfusion-dependent patients with deletion 5q, with 67 % achieving transfusion 
independence after a median interval of 4.6 weeks of treatment. Cytogenetic 
responses were observed in 73% of patients with complete cytogenetic remission 
in 45% patients. Both transfusion response and cytogenetic response frequency 
were independent of karyotype complexity, raising excitement that this new 
treatment strategy might favorably alter the natural history of disease in 
higher risk patients with deletion 5q. Lenalidomide was approved by the U.S. 
Food and Drug Administration on December 27, 2005, for the treatment of IPSS Low 
and intermediate-1 risk MDS patients with del(5q) abnormality. A phase III 
Intergroup trial (ECOG 2905) will test the capacity to potentiate erythropoietin 
response by comparing response to lenalidomide monotherapy to the combination of 
darbepoetin and lenalidomide in non-deletion 5q MDS patients.