Waldenström Macroglobulinaemia — IgM, Hyperviscosity and Targeted Therapy

Diagnosis and complications

Diagnosis requires bone marrow assessment with lymphoplasmacytic infiltration and an IgM monoclonal protein. MYD88 L265P and CXCR4 testing support diagnosis and treatment selection. Hyperviscosity, cryoglobulinaemia, cold agglutinin disease and neuropathy are important complications to assess at baseline and during follow-up.

• Bone marrow aspirate and biopsy
• Serum protein electrophoresis and immunofixation
• MYD88 and CXCR4 mutation testing
• Serum viscosity when symptoms suggest hyperviscosity
• Cryoglobulin and cold agglutinin assessment where indicated

When and how to treat

Asymptomatic patients are observed. Treatment is considered for cytopenias, bulky or symptomatic disease, hyperviscosity or neuropathy. Options include rituximab-based therapy, BTK inhibitors, proteasome inhibitor combinations and chemoimmunotherapy. Plasmapheresis is used for symptomatic hyperviscosity. Response is monitored with IgM levels and clinical measures.

• Observation for asymptomatic disease
• Rituximab-based or BTK inhibitor therapy
• Plasmapheresis for symptomatic hyperviscosity
• Avoid unnecessary transfusions that may raise viscosity
• Long-term monitoring for transformation

Guidelines referenced:

• NCCN Guidelines — Waldenström Macroglobulinaemia
• IWWM consensus recommendations
• WHO Classification of Haematopoietic and Lymphoid Tissues