Lenalidomide-based immunochemotherapy

Together with pomalidomide (Pomalyst, initially known as CC-4047), lenalidomide (Revlimid, initially known as CC-5013) is a synthetic derivative of thalidomide (Thalomid) originally developed in the 1990s to achieve improved potency in the absence of significant side effects. As a matter of fact, in 1957, the release of thalidomide as an over-the-counter sedative, tranquilizer, and antiemetic for morning sickness in Germany was followed by a peak of infants born with malformations of the limbs (phocomelia), resulting in the rapid withdrawal of the drug from the market. Similar measures were rapidly undertaken worldwide, with Canada being the last country to discontinue the use of the drug (in 1962). Current estimates indicate that 10,000–20,000 cases of phocomelia recorded in 46 countries in the late 1950s and early 1960s can be attributed to thalidomide. Irrespective of its high teratogenic potential, the interest around thalidomide increased again in the 1990s, following the demonstration that this agent significantly inhibits the production of tumor necrosis factor α (TNFα), a pro-inflammatory cytokine involved in the etiology of erythema nodosum leprosum (ENL, a complication of leprosy). In 1998, the US Food and Drug Administration (FDA) authorized Celgene Corp. to market thalidomide for the treatment of ENL patients, provided that the drug would be distributed under a strict control. Approximately in the same period, the combination of thalidomide with dexamethasone (a glucocorticoid) turned out to mediate robust antineoplastic effects in subjects affected by some hematological malignancies, eventually leading to the accelerated approval of this regimen by the US FDA for use in newly diagnosed multiple myeloma (MM) patients (in 2006). Alongside, the development and (pre)clinical characterization *Correspondence to: Lorenzo Galluzzi; Email: deadoc@vodafone.it; Guido Kroemer; Email:kroemer@orange.fr Submitted: 09/14/2013; Accepted: 09/14/2013 Citation: Semeraro M, Vacchelli E, Eggermont A, Galon J, Zitvogel L, Kroemer G, Galluzzi L. Trial Watch: Lenalidomide-based immunochemotherapy. OncoImmunology 2013; 2:e26494; http://dx.doi.org/10.4161/onci.26494 Trial Watch Lenalidomide-based immunochemotherapy