Blood reviews
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New effective strategies are required that specifically address the challenges of multiple myeloma (MM) treatment, namely, disease recurrence, immunosuppression, and treatment-related toxicities. Recent preclinical and clinical findings suggest that the IMiDs® immunomodulatory compound lenalidomide has a dual mechanism of action, involving both a direct tumoricidal activity and immunomodulation, which may result in rapid and sustained control of MM, respectively. The tumoricidal effect of lenalidomide occurs through several mechanisms, including disruption of stromal support, induction of tumor suppressor genes, and activation of caspases. ⋯ Lenalidomide in combination with dexamethasone synergistically inhibits proliferation and induces apoptosis; however, dexamethasone appears to antagonize the immune-enhancing effect of lenalidomide. A study has demonstrated that a regimen of lenalidomide in combination with an optimal dose and schedule of dexamethasone may increase survival by allowing synergistic antiproliferative effects, without affecting immunomodulatory activity. As preclinical and clinical research continue, additional insights into the dual mechanism of action of lenalidomide will help to further optimize the use of lenalidomide in MM.