Waldenstrom’s Macroglobulinemia

Waldenstrom’s macroglobulinemia (WM) is a lymphoid neoplasm resulting from the accumulation, predominantly in the marrow, of a clonal population of lymphocytes, lymphoplasmacytic cells, and plasma cells, which secrete a monoclonal immunoglobulin (Ig) M protein. WM presentation varies and can include cytopenias, as well as morbidity from the IgM paraprotein itself including peripheral neuropathy, cold agglutinemia, cryoglobulinemia, and hyperviscosity. Highly recurring mutations in MYD88 and CXCR4 are found in >90% and 30-40% of WM patients, respectively, and can impact disease presentation as well as therapy. MYD88 mutations trigger Bruton’s tyrosine kinase, a target of ibrutinib, while CXCR4 mutations contribute to drug resistance. Treatment with the monoclonal antibody rituximab alone or in combination with alkylators, proteasome inhibitors, or nucleoside analogues, as well as ibrutinib, is commonly used in the treatment of WM patients. Choice of treatment is impacted by goal of treatment, and avoidance of stem cell toxicity in younger autologous transplant-eligible WM patients.