Lymphoplasmacytic lymphoma is an indolent B-cell, non-Hodgkin lymphoma (NHL), the majority of which are characterized by production of a monoclonal immunoglobulin M (IgM) protein and are known as Waldenström macroglobulinemia. Identification of highly recurrent activating somatic mutation in MYD88 has improved our understanding of the pathogenesis of Waldenström macroglobulinemia and has therapeutic implications. Here, we review novel therapeutic agents in Waldenström macroglobulinemia/lymphoplasmacytic lymphoma, which have emerged in the past decade and discuss their comparative efficacy and safety, with emphasis on a Bruton's tyrosine kinase (BTK) inhibitor, which has been recently approved by the US FDA, specifically for Waldenström macroglobulinemia/lymphoplasmacytic lymphoma. Future research should focus on identifying targeted agents against activating mutations and long-term data for currently available novel agents should be critically evaluated, both in treatment-naïve and in relapsed/refractory settings.
Keywords: BTK inhibitors; HDAC inhibitors; MYD88L265P; PI3K/AKT/PKC inhibitors; Waldenström macroglobulinemia; bendamustine; immunomodulators; mTOR inhibitors; proteasome inhibitors.