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Waldenström macroglobulinemia.

Waldenström macroglobulinemia (WM) is an indolent low-grade lymphoma characterized by bone marrow infiltration with lymphoplasmacytic cells associated with a monoclonal immunoglobulin M protein. It is considered incurable. The 5-year survival rate for patients with symptomatic WM is 87% for those with low-risk disease, 68% for those with intermediate-risk disease, and 36% for those with high-risk disease. Owing to recent advances in therapy with new targeted treatment options, relative survival has improved. Insights into mutations in MYD88 L265P and the WHIM-like CXCR4 have been shown to be significant not just in terms of their diagnostic and prognostic value, but also as potential targets for therapy. For patients with symptomatic WM, the different classes of agents used to treat WM include alkylating agents (eg, cyclophosphamide and chlorambucil), nucleoside analogues (eg, cladribine and fludarabine) and monoclonal antibodies (eg, rituximab and alemtuzumab). With an increasing number of novel treatment options available including everolimus, bendamustine, bortezomib, ibrutinib, carfilzomib, lenalidomide, and panobinostat, the optimal timing and introduction of these options in the absence of phase 3 trials remains controversial. A treatment algorithm based on Mayo Stratification for Macroglobulinemia and Risk-Adapted Therapy (mSMART) and a comparison of important clinical trials in WM is provided.

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