Haema 2013; 4(2):161-170
by Efstathios Kastritis, Evangelos Terpos, Meletios A. Dimopoulos
Therapeutic Clinic, University Medical School of Athens, Greece
Abstract
Waldenström’s macroglobulinemia (WM) is a rare B-cell malignancy characterized by the infiltration of the bone marrow by a lymphoplasmacytic clone producing IgM monoclonal immunoglobulin. An important advance in the elucidation of the biology of the disease is the recently recognized somatic mutation in the MYD88 gene (L265P), which is present in >90% of patients with symptomatic MW. The clinical signs and symptoms of the disease are related to the direct infiltration of the bone marrow or other lymphoid organs by the tumor clone and the quantity and the physicochemical and immunological properties of the monoclonal IgM. The most frequent clinical and laboratory findings of symptomatic disease include cytopenias (mostly anemia), B-symptoms, neuropathy, hyperviscosity syndrome and, less frequently, significant lymphadenopathy or splenomegaly. The most important decision in the management of patients with WM is the identification of patients with symptomatic disease. Individuals with IgM-MGUS should be monitored lifelong, while patients with asymptomatic MW should not be treated as the disease can remain stable for many years. The decision to start therapy should be based on the presence of certain signs or symptoms, such as B-symptoms, IgM-related complications, bulky lymphadenopathy or splenomegaly, cytopenias or evidence of transformation of the disease. It should be noted that serum levels of monoclonal IgM alone should not be used as a criterion to initiate treatment. The treatment strategy should be individualized. Initiation of plasmapheresis is indicated for patients with hyperviscosity syndrome. Combinations of rituximab with chemotherapy are the preferred initial regimens for most patients with WM. In patients with high levels of IgM, rituximab may be associated with a transient increase in IgM («IgM flare»), and plasmapheresis may be required for symp- tomatic hyperviscosity. Bortezomib-based regimens are effective, act rapidly and may be an option for patients with high IgM levels, but are associated with increased risk of neurotoxicty. Combinations based on nucleoside analogs are very active, but their toxicity makes them a choice for selected patients only. The combination of rituximab with bendamustine is a particularly effective therapy, with manageable toxicity and may be associated with better outcomes than regimens such as R-CHOP. Younger patients may also be candidates for ASCT, although this procedure is not recommended as first-line therapy in WM. In case of relapse, the choice of salvage therapy depends on the type of prior treatment, tolerance, quality and duration of response to first-line therapy, age of the patient, the candidacy for ASCT and, of course, patient preferences. Treatment options include combinations based on bendamustine, bortezomib, nucleoside analogs and/or newer drugs, while in younger patients ASCT may have a role as salvage therapy in chemosensitive disease.