Novel therapeutic approaches to cryoglobulinemia: Imatinib, infliximab, bortezomib, and beyond

Cryoglobulinemia is a rare disorder characterized by the development of leukocytoclastic necrotizing vasculitis. Currently, the conventional treatment of cryoglobulinemia in the absence of viral infection involves corticosteroids, immunosuppressive drugs, and plasma exchange. Patients with relapsed or refractory disease require additional therapies, but no established guidelines regarding the treatment of these patients are available. The recent molecular revolution has resulted in an armamentarium of targeted biologic agents, and several of these novel drugs have been shown to be active in patients with refractory cryoglobulinemia. This chapter reviews the clinical results and rationale of several emerging agents for cryoglobulinemia, including TNF inhibitors, the immunomodulator drugs thalidomide and lenalidomide, and the proteasome inhibitor bortezomib.