Title: Novel insights into the mechanism of action of lenalidomide
Abstract: Lenalidomide (Revlimid®) is a synthetic derivative of thalidomide (Thalomid®) currently licensed by the US Food and Drug Administration (FDA) and other international regulatory agencies for the treatment of multiple myeloma (MM) (in combination with dexamethasone)1-3 and low or intermediate-1 risk myelodysplastic syndromes bearing 5q cytogenetic abnormalities (as a standalone agent).4-6 Lenalidomide was originally developed to improve the safety profile of thalidomide, which eventually turned out to be responsible for an estimated number of 10 000–20 000 phocomelic babies worldwide in the 1950–60s.7 As compared with thalidomide, lenalidomide is associated with limited neurotoxic activity, but is not completely devoid of teratogenic effects.8-10 For this reason, both thalidomide (which is also approved for use in MM patients, together with dexamethasone)11 and lenalidomide are commercialized under tightly controlled distribution programs (as per explicit request of the US FDA).8 Recently, a novel thalidomide derivative, pomalidomide (Pomalyst®), has been approved for the treatment of specific subsets of MM patients, including individuals who progressed on or shortly after thalidomide therapy.12,13 At odds with thalidomide and lenalidomide, pomalidomide exerts very limited (if any) teratogenic activity.14