Lenalidomide (Revlimid, CC-5013) is a second-generation synthetic derivative of glutamic acid and thalidomide analogue with antiangiogenic, antitumorigenic, and immun-omodulating activity that was realized due to anecdotal im-munomodulatory activity in erythema nodosum leprosum (ENL) and in autoimmune disorders. Creation of synthetic modifications to the thalidomide backbone led to the discovery of lenalidomide and pomalidomide with 500-fold greater immunomodulatory potency and safer side effect profile compared to the parent drug. Use of lenalidomide in proliferative neoplasms has recently intensified due to the agent's success in MM and MDS where it acts to alter immune homeostasis and modulate inflammation within the bone marrow microenvironment. Studies in relapsed and refractory B-cell chronic lymphocytic leukemia (B-CLL) as well as non-Hodgkin's lymphoma (NHL) solid malignancies such as central nervous system, ovarian, and renal cell carcinoma demonstrate the potential of this drug in diverse neoplastic processes. While the molecular antitumor mechanism and specificity have been extensively studied in preclinical and clinical settings, the future application and design of effective therapeutic combinations with lenalidomide is dependent on understanding the immunomodulatory mechanism and anti-inflammatory properties in the context of the bone marrow milieu, the microenvironmental interactions, and bioactivity within adaptive and innate immune cells.
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