CC-122 is the first-in-class pleiotropic pathway modifiers that may work by binding cereblon and promoting the ubiquitination and the resulting degradation of the transcription factors Aiolos and Ikaros. It has been shown to have potent anti-proliferative, anti-angiogenic and immunomodulatory activities in B cell lymphoma, perhaps though its T and NK-cell activation and B-cell inhibition. CC-122 inhibits proliferation and induces apoptosis in a broad panel of diffuse large B-cell lymphoma cell lines, reduces tumor growth in xenograft models established from activated B-cell (ABC) and germinal center B-cell DLBCL cell lines, and stimulates IL-2 production in primary T cells. These activities are dependent on the binding of CC-122 to Cereblon and subsequent ubiquitination and proteasomal degradation of Aiolos and Ikaros, resulting in direct derepression of interferon (IFN)–stimulated gene (ISG) transcription and induction of IFN-inducible proteins, ultimately leading to apoptosis.