Novel treatment options for Waldenström macroglobulinemia.

Waldenström macroglobulinemia (WM), first described by Jan Waldenström in 1944, is a lymphoplasmacytic lymphoma characterized by the presence of an immunoglobulin M monoclonal gammopathy in the blood and monoclonal small lymphocytes and lymphoplasmacytoid cells in the bone marrow. WM is a rare and indolent disease but remains incurable. In this review we discuss the pathogenesis of WM and focus on novel treatment options that target pathways deregulated in this disease. Recent studies have helped us identify specific genetic mutations that are commonly seen in WM and might prove to be important therapeutic targets in the future. We discuss the role of epigenetics and the changes in the bone marrow microenvironment that are important in the pathogenesis of WM. The commonly used drugs are discussed with a focus on novel agents that are currently being used as single agents or in combination to treat WM. We finally focus on some agents that have shown preclinical efficacy and might be available in the near future.