POMALIDOMIDE

12.1 Mechanism of Action Pomalidomide is an analogue of thalidomide with immunomodulatory, antiangiogenic, and antineoplastic properties. Cellular activities of pomalidomide are mediated through its target cereblon, a component of a cullin ring E3 ubiquitin ligase enzyme complex. In vitro, in the presence of drug, substrate proteins (including Aiolos and Ikaros) are targeted for ubiquitination and subsequent degradation leading to direct cytotoxic and immunomodulatory effects. In in vitro cellular assays, pomalidomide inhibited proliferation and induced apoptosis of hematopoietic tumor cells. Additionally, pomalidomide inhibited the proliferation of lenalidomide-resistant multiple myeloma (MM) cell lines and synergized with dexamethasone in both lenalidomide-sensitive and lenalidomide-resistant cell lines to induce tumor cell apoptosis. Pomalidomide enhanced T cell- and natural killer (NK) cell-mediated immunity and inhibited production of pro-inflammatory cytokines (e.g., TNF-α and IL

Contraindications

• • the patient should be apprised of the potential risk to a fetus. 4.2 Hypersensitivity Pomalidomide Capsules are contraindicated in patients who have demonstrated severe hypersensitivity (e.g.
• • angioedema
• • anaphylaxis) to pomalidomide or any of the excipients [see Warnings and Precautions (5.7 )
• • Description (11) ].