Novel lenalidomide-based combinations for treatment of multiple myeloma.

Lenalidomide (LEN) is an immunomodulatory drug (IMiD) which exerts tumoricidal effects and has immunomodulatory, anti-inflammatory and anti-angiogenic properties that synergistically keep the tumor in remission. It is currently approved as second-line therapy for multiple myeloma (MM) and for 5q defective myelodysplastic syndrome, while ongoing studies are at present evaluating its role in both solid and hematologic malignancies. Based on its high activity as an anti-myeloma drug with a good tolerability profile, LEN is currently gaining interest in both preclinical and clinical research for combinatory treatments with novel agents including monoclonal antibodies, immunotoxins, tyrosine kinase inhibitors, new proteasome inhibitors and epigenetic-interfering agents as well as with new compounds targeting the cancer stem cell niche. Preliminary data from clinical studies are encouraging and suggest a favorable safety profile, although the long-term tolerability of these combinatory regimens needs to be carefully evaluated since an increased incidence of new primary tumors associated with LEN treatment has recently been reported. Thus, from bench to bedside studies are required to design clinical trials for new drug combination approval.