Waldenström macroglobulinemia (WM) is a low-grade lymphoplasmacytic lymphoma of mature IgM+
B-lymphocytes that remains incurable despite recent practice-altering therapeutic advances and refinements in patient care. Defining features of WM include symptoms that can either be attributed to the extent and site of tissue infiltration by tumor cells or the magnitude and immunological specificity of the monoclonal serum IgM (paraprotein). Current guidelines for the therapeutic stratification of patients with newly diagnosed WM recommend BR (bendamustin-rituximab) for bulky and/or symptomatic disease. DRC (dexamethasone-rituximab-cyclophosphamide) is a good treatment option for relapsed or refractory WM. Ibrutinib – a small-drug inhibitor of Bruton tyrosine kinase, approved for WM treatment in the United States and Europe in 2015 – is particularly effective for tumors that harbor the hallmark MYD88L265P
mutation. Plasma exchange is indicated in patients with IgM-dependent hyperviscosity syndrome. The potential development of novel drugs and combination regimens generates promise that the future of patients with WM is bright.