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The IMiD agents, lenalidomide and pomalidomide, have immunomodulatory properties that have been demonstrated in preclinical studies.1-4 IMiD agents have been found to increase activation and proliferation of T cells, production of IL-2, and activity of CD8+ effector T cells.1-3 Stimulation and expression of natural killer (NK) cells, NK cell–mediated lysis via antibody-dependent cell-mediated cytotoxicity, and direct NK cell–mediated killing were also enhanced by IMiD agents.2,4 These data and others have led Celgene to evaluate the role of lenalidomide and pomalidomide in combination with various agents in multiple myeloma.
In addition to immunomodulatory properties, IMiD agents are hypothesized to have multiple mechanisms of action, including tumoricidal and antiangiogenic activity.5
Preclinical studies demonstrated increased anti-myeloma activity of IMiD agents in combination with dexamethasone and certain proteasome inhibitors and monoclonal antibodies.10-18