Onkológia 5/2016

Waldenström’s macroglobulinemia in 2016: in order to optimize immunochemotherapy minimizing side effects

Waldenström‘s macroglobulinemia (WM) is clonal B-cell lymphoproliferative disorder characterized by monoclonal immunoglobulin M protein and bone marrow infiltration by small lymphocytes with plasmacytic differentiation, meeting the diagnostic criteria of lymfoplasmacytic lymphoma. Although WM is incurable with current therapies, it is moderately indolent, chronic disease with overall good prognosis. Mortality of asymptomatic patients is similar to that of general population. Delaying treatment until symptoms develop can limit its potential side effects. Rituximab, monoclonal anti-CD20 antibody in combinations with other agents form the backbone of treatment. Even if there is no standard therapy for WM, there is a general preference for regimens with safer toxicity profile. Primary goal of therapy is long term disease control with maintaining patient´s quality of life. And at the same limitation of exposure of toxic and prolonged treatment. Treatment protocols with vinca alkaloids, anthracyclines and purine analogs are considered as inappropriate in front-line setting. Dexamethasone, rituximab, cyclophosphamide (DRC) and bendamustine, rituxmab (BR) are well tolerated combinations. Alternative option is bortezomib, dexamethasone, rituximab (BDR). Subcutaneous aplication of bortezomib in weekly schedule is possibly more appropriate, because of typical predisposition for neuropathic complications in WM patients. These regimens are associated with remisions of 3 to 6 years. Original treatment can be repeated in case of symptomatic relapse after more than 1 to 2 years from initial therapy. Alternative regimen is used in case of earlier relapse. Besides aforementioned front-line regimens, there are other options for relapsed WM treatment as ibrutinib, immunomodulatory drugs (thalidomide, lenalidomide), carfilzomib and everolimus. Because of association with secondary malignancies, purine analogs should be reserved for older patients and multiple relapse treatment. For selected younger patients, high-dose chemotherapy with rescue autologous stem cell transplant is an option. Ideally for treatment of early relapsed WM. International prognostic scoring system for WM helps to identify patients with high risk of relapse. Early stem cell mobilization after first remision is suitable for this group of patients.

Keywords: Waldenström‘s macroglobulinemia, immunochemotherapy, side effects, optimalization of treatment, rituximab, dexamethasone, cyclophosphamide, bendamustine, bortezomib