Background: 3.2-3.5% of persons over age 50 have a monoclonal gammopathy. Monoclonal gammopathies have many causes, including cancer. 10-20% of monoclonal gammopathies are of isotype IgM. A systematic approach to the differential diagnosis of IgM gammopathies is essential because of the different therapeutic implications of the various underlying conditions.
Methods: This review is based on pertinent publications retrieved by a selective search in PubMed and current guidelines from Germany and abroad.
Results: The diagnosis of a monoclonal IgM gammopathy is established by serum electrophoresis in combination with immune fixation. Further evaluation enables the identification of the underlying condition: the differential diagnosis includes IgM-MGUS (monoclonal gammopathy of unclear significance), Waldenström's disease, and IgM myeloma. The therapeutic implications of the under - lying condition vary from watchful waiting in IgM-MGUS to combined rituximab and antineoplastic chemotherapy (off-label first-line use of rituximab) in symptomatic Waldenström's macroglobulinemia. Ibrutinib has been approved for the treatment of patients with recurrences, or of those for whom first-line treatment with rituximab and chemotherapy is not suitable. The current treatment options do not result in cure. In symptomatic Waldenström's disease, the goal of treatment is to keep the disease under control for as long as possible without impairing the patient's quality of life.
Conclusion: Evidence-based treatment decisions in Waldenström's macroglobulinemia now rely mainly on small-scale, single-armed trials. Patients with this disease should be treated in the setting of a clinical trial if possible. Trials aimed at improving the quality of treatment for other IgM-associated diseases, such as IgM neuropathies and cold agglutinin disease, would also be desirable.