From the Guidelines
Waldenström macroglobulinemia (WM) typically follows an indolent clinical course characterized by gradual progression over many years, with a median survival of 5-10 years, though many patients live much longer with appropriate management, as reported in the most recent guidelines 1. The disease begins with an asymptomatic phase that may last for years, during which patients have detectable IgM monoclonal protein but no symptoms. As the disease progresses, patients develop symptoms related to:
- Bone marrow infiltration (anemia, thrombocytopenia, neutropenia)
- Hyperviscosity syndrome (visual disturbances, headaches, dizziness, bleeding)
- Tissue infiltration (hepatosplenomegaly, lymphadenopathy) Treatment is not initiated until patients become symptomatic, with common indications including:
- Hemoglobin <10 g/dL
- Platelets <100,000/μL
- Symptomatic hyperviscosity
- Neuropathy
- Amyloidosis
- Bulky lymphadenopathy First-line treatment typically involves:
- BTK inhibitors like ibrutinib (420 mg daily) or zanubrutinib (160 mg twice daily)
- Chemoimmunotherapy regimens such as bendamustine plus rituximab (bendamustine 90 mg/m² days 1-2, rituximab 375 mg/m² day 1, every 28 days for 4-6 cycles), as recommended by the Mayo Clinic guidelines 1 Disease monitoring involves regular assessment of:
- IgM levels
- Complete blood counts
- Clinical symptoms The choice of initial therapy is critical, and the DRC regimen (dexamethasone, rituximab, and cyclophosphamide) is a recommended option, with an objective response rate of 83% and a 2-year progression-free survival rate of 90%, as reported in a study published in the Mayo Clinic Proceedings 1. In patients with symptomatic hyperviscosity, plasmapheresis should be promptly initiated before cytoreduction, and stem cell harvest for future use may be considered in first remission for patients 70 years or younger who are potential candidates for autologous stem cell transplantation, as recommended by the JAMA Oncology guidelines 1.
From the Research
Clinical Course of Waldenström Macroglobulinemia
The clinical course of Waldenström macroglobulinemia (WM) is characterized by:
- An indolent disease course, with many patients being candidates for careful monitoring 2
- Advanced age and nonspecific constitutional symptoms at presentation, requiring careful consideration of treatment decisions 2
- Clinical features including anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity 3, 4, 5
Diagnosis and Risk Stratification
Diagnosis of WM is confirmed by:
- Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow 3, 4, 5
- Detection of the L265P mutation in MYD88, which is found in more than 90% of patients 3, 4, 5
- Characteristics predictive of outcomes include age, hemoglobin level, platelet count, β2 microglobulin, lactate dehydrogenase (LDH), and monoclonal IgM concentrations 3, 4, 5
Management and Treatment
Management of WM involves:
- Observation until symptoms develop for patients who do not require immediate therapy 3, 4, 5
- Combination regimens, such as chemoimmunotherapy or covalent Bruton tyrosine kinase inhibitors, as recommended first-line therapy 3
- Rituximab-monotherapy being inferior to combination regimens 3, 4, 5
- Reduction of therapy toxicity being an important part of treatment selection, given WM's natural history 3, 4, 5