Combination CC-5013 and rapamycin overcomes the protective effect of IL-6, IGF-1, and adherence to the bone marrow microenvironment. Rapamycin-induced cytotoxicity is abrogated in the presence of cytokines, but the combination of CC-5013 with rapamycin overcomes the protective effects of (A) IL-6 and (B) IGF-1. (C) Combined therapy was also effective at inhibiting DNA synthesis in MM1.S cells adherent to BMSCs.