Current and future therapeutic approach for Waldenström's macroglobulinemia.

Waldenström's macroglobulinemia is a rare B-cell malignancy defined by medullar infiltration by clonal lymphoplasmocytic cells and monoclonal IgM secretion. Treatment is reserved for symptomatic patients. The main first-line treatment strategies combine immunotherapy (principally the anti-CD20 monoclonal antibody rituximab) with chemotherapeutic agents, including alkylating agents, purine analogs and/or bortezomib. The overall response rate to these conventional treatments is between 70 and 90%, but a cure cannot be expected. For patients with relapsed or refractory disease, drugs that were not used for first-line treatment and other agents such as immunomodulators can be tried, but the response rate is generally lower and the responses are shorter lived. Recently, advances in our understanding of the biology of Waldenström's macroglobulinemia have led to the development of new drugs targeting hyperactive pathways. This review focuses on current treatment options and on new therapeutic developments.