Waldenstrom's macroglobulinemia and its individualized therapy options

Waldenstrom's macroglobulinaemia is a form of lymphoplasmocytic lymphoma that preferentially localizes to the bone marrow and causes a special syndrome characterized by monoclonal IgM hypersecretion. Recent results point to the fact that this disease has at least three different pathobiological forms with different clinical presentation. While mutations of MYD88 occur in 95-97% of the cases, there are CXCR4 mutations in 30-40%, ARID1A mutations in 17% and CD79B mutations in approximately 10% of afflicted individuals. CXCR pathway signaling is able to transcriptionally silence tumor suppressors induced by MYD88 activation. Patients with mutated MYD88 and CXCR4 present with higher tumor burden, slower developing and less deep response upon therapy with more frequent resistance. In this review, based on the most recent data, a treatment selection advice is provided for the therapy of symptomatic patients.