How we manage patients with Waldenström macroglobulinaemia

Abstract

Waldenström macroglobulinaemia (WM) is a rare, indolent B-cell lymphoproliferative disorder characterized by cellular involvement in bone marrow and monoclonal IgM production. Symptoms can be related to cytopenias, tumoural involvement, or IgM-related disorders. Somatic mutations in the MYD88 gene have been described in the majority of WM cases. The mutation is responsible for a gain-of-function and induces activation of nuclear factor-κB, for DNA transcription and cell survival. It seems that MYD88 mutation is associated with better prognosis and better response to some treatment. Treatments are started when WM is symptomatic, following systematic biological and morphological assessments. Therapeutic choice depends on age, frailty and urgent efficacy need. In first line, the majority of patients are treated with monoclonal anti-CD20 antibody-based regimens combined with cytotoxic chemotherapy. Rituximab, cyclophosphamide and dexamethasone remain the most commonly used regimen with good safety. Nevertheless, increasing numbers of new drugs are becoming available or are in development. Proteasome inhibitors, such as bortezomib or carfilzmib, showed good and rapid responses. Bruton tyrosine kinase (BTK) inhibitor demonstrated excellent results and is now available for relapse/refractory disease or as first line for some patients. This review highlights the diagnostic procedures and therapeutic approaches in WM.

How Recent Advances in Biology of Waldenström’s Macroglobulinemia May Affect Therapy Strategy

“…In many cases, the diagnosis is fortuitous and there is no need for immediate therapeutic intervention. Criteria for treatment initiation are cytopenia (BM involvement, immunological destruction, or chronic inflammation), constitutional symptoms, hyperviscosity syndrome, and complications related to IgM activity (anti-myelin-associated glycoprotein (MAG) neurop-athy, cold agglutinins disease ...), or to deposits (AL amyloidosis ...) [1].…”

Bilateral Sudden Sensorineural Hearing Loss in Waldenström’s Macroglobulinemia: Case Report and Review of the Literature

“…1 It is a rare entity representing 1 to 2% of all hematological malignancies and 6% of the lymphoproliferative syndromes. 2 The incidence is estimated to be three new cases per 1 million individuals, with men affected roughly twice as often as women, and the median age of diagnosis being 70 years. 3 While the etiology remains unclear, various risk factors have been identified including the presence of monoclonal gammopathy of undetermined significance, family history, and autoimmune diseases.…”

“…3 While the etiology remains unclear, various risk factors have been identified including the presence of monoclonal gammopathy of undetermined significance, family history, and autoimmune diseases. 2,4 Clinical presentation is highly variable. Bone marrow infiltration can induce cytopenias; however, involvement of lymph nodes, spleen, or liver is less frequent than with other lymphomas.…”

Combined Immunosuppressive Therapy Induces Remission in Patients With Severe Type B Insulin Resistance: A Prospective Cohort Study

“…This treatment regimen was designed to eliminate the autoantibodies by targeting CD20 B cells with rituximab, decreasing preformed plasma cells using high-dose pulsed steroids, and nonspecific T-cell– and B-cell–directed immunosuppression with cyclophosphamide or cyclosporine. This therapeutic regimen has been proven successful in other autoimmune disorders, such as immune cytopenias associated with chronic lymphocytic leukemia (31), as well as lymphoproliferative disorders such as Waldenström macroglobulinemia (32,33), chronic lymphocytic leukemia (34), and monoclonal Ig deposit–related glomerulopathy (35).…”