Pomalidomide

Pomalidomide (CC-4047 or Actimid), is a derivative of thalidomide that is anti-angiogenic and also acts as an immunomodulator. Pomalidomide was able to directly inhibit both the tumor cell and vascular compartments of myeloma cancers. This dual activity of pomalidomide makes it more efficacious than thalidomide in vitro and in vivo. Pomalidomide inhibits the growth of T regulatory cells which is stimulated by IL-2 with an IC50 of ~1 μM. In vivo, Pomalidomide treatment of drug resistant myeloma cell tumors in mice was able to produce complete and sustained regressions without any observed toxicity. Additionally, Pomalidomide (CC-4047) induced complete regressions of Burkitt's lymphoma cell tumors. Pomalidomide enhances the antitumor effect of rituximab against B-cell lymphomas in severe combined immunodeficient mice. Phase III results showed significant extension of progression-free survival (median 3.6 months vs. 1.8 months; P < 0.001), and overall survival in patients taking pomalidomide and dexamethasone.