Waldenström macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma that mainly affects elderly patients. Complications of the disease are usually attributable to tumor load or the presence of monoclonal immunoglobulin M (IgM). With limited approved treatment options by the US Food and Drug Administration (FDA), the demand for new therapies is high.

In a review published in Blood, Meletios A Dimopoulos, MD, and Efstathios Kastritis, MD, of the department of clinical therapeutics at the University of Athens in Greece, summarized current literature surrounding the treatment of WM.1 They also reviewed several example cases using clinical data from their institution.

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Diagnostic Workup and Indication for Therapy

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If the presence of IgM is confirmed by immunofixation electrophoresis, and a bone marrow biopsy reveals infiltration with clonal lymphoplasmacytic cells, a diagnosis of WM is established. Indolent cases are defined as those with less than 10% clonal infiltrate, but there is no established threshold for the amount of clonal cell infiltrate required for diagnosis. Although variation in clonal morphology is high, established cell morphology and immunophenotypic criteria aid in differential diagnosis among other conditions that exhibit a similar phenotype.1

During the initial workup, ruling out other causes of presenting symptoms is important. At initial presentation, the most common symptoms are anemia and cytopenias (42%), B symptoms (25%), and hyperviscosity (17%). As a result, additional laboratory parameters should be measured, including iron studies, serum albumin, lactate dehydrogenase, and beta-2 microglobulin. The measurement of monoclonal IgM levels is also necessary, as hyperviscosity syndrome, a key marker of symptomatic disease, is related to elevated IgM levels; however, this relationship is not linear.1

Another common complication of the disease is peripheral neuropathy, which in many cases is the sole indication for treatment in asymptomatic patients. WM-associated neuropathy is often slowly progressing, sensory, and symmetrical in nature. Hence, rapidly progressing peripheral neuropathy may indicate an unrelated cause.

Because of a prolonged asymptomatic period, often exceeding 5 to 10 years, it is crucial to ensure patients have an indication for therapy. Though some clinical and laboratory indications have been proposed, clinical judgment is often necessary. Monoclonal IgM levels alone are insufficient to determine an indication for therapy. Currently, there are no data to help guide clinical decision making on whether to delay or commence therapy in asymptomatic patients. In these cases, enrollment into a clinical trial may be a suitable option.