About Waldenström’s macroglobulinaemia (WM)
Waldenström’s macroglobulinaemia is a rare, slow-growing blood cancer classified as a lymphoplasmacytic lymphoma. It arises from B-cells that mature into plasma cells, which then produce excessive amounts of IgM antibodies. These large antibodies thicken the blood, leading to hyperviscosity syndrome and impaired circulation.
WM shares features with:
- Indolent non-Hodgkin lymphoma (slow progression)
- Myeloma (plasma cell involvement), though it does not cause bone damage like myeloma
Who gets WM?
- Incidence ~2% of all blood cancers
- Age – most commonly diagnosed in people over 60
- Gender – more frequent in men
- Ethnicity – slightly more common in people of Northern European descent
Causes of Waldenström’s macroglobulinaemia (WM)
The precise cause remains unknown, but several factors are associated:
Genetic mutations
- MYD88 L265P mutation: Found in >90% of WM cases; drives abnormal cell growth
- CXCR4 mutations: Present in ~30–40%; linked to more aggressive disease and treatment resistance
Other risk factors
- Family history of B-cell disorders
- Exposure to certain environmental toxins (pesticides)
- Autoimmune conditions (less common)
Symptoms of Waldenström’s macroglobulinaemia (WM)
Symptoms develop gradually and vary by individual. They result from:
- Accumulation of abnormal lymphocytes
- Excess IgM in the blood
Common symptoms
- Fatigue, weakness, weight loss
- Anaemia: dizziness, paleness, shortness of breath
- Recurrent infections
- Easy bruising or bleeding
Organ-related symptoms
- Enlarged spleen (pain under left ribs)
- Swollen lymph nodes (neck, armpits, groin)
Hyperviscosity symptoms
- Headaches, blurred vision, confusion
- Hearing loss, sleepiness
- Neuropathy (nerve damage)
- Kidney dysfunction
Diagnosis of Waldenström’s macroglobulinaemia (WM)
Diagnosis involves multiple tests:
Blood tests
- Full Blood Count (FBC): Checks red/white cells and platelets
- Serum Protein Electrophoresis: Measures IgM levels
- Immunofixation: Identifies monoclonal IgM
Bone marrow biopsy
- Confirms presence of lymphoplasmacytic cells
- Assesses tumor burden
Genetic testing
- Detects MYD88 and CXCR4 mutations
Imaging
- CT or PET scans to evaluate lymph node and organ involvement
Types of WM
WM is generally considered a single disease entity, but it can be categorized based on:
Clinical Presentation
- Smoldering WM – no symptoms, stable IgM levels
- Symptomatic WM – active disease requiring treatment
Genetic Subtypes
- MYD88-mutated WM – most common, better response to BTK inhibitors
- CXCR4-mutated WM – may require alternative therapies
Stages of WM
Unlike other cancers, WM is not staged. Instead, disease progression is assessed based on:
- Amount abnormal cells in bone marrow and lymph nodes
- IgM levels in blood
- Organ involvement (spleen, kidneys, nervous system)
- Symptoms – especially hyperviscosity or cytopenias
Patients are categorized as:
- Asymptomatic (smoldering WM) – no treatment needed
- Symptomatic WM – requires treatment
Prognosis of Waldenström’s macroglobulinaemia (WM)
WM is incurable, but manageable. Prognosis depends on:
- Age and overall health
- Genetic mutations (MYD88 vs. CXCR4)
- Response to treatment
- Presence of complications (e.g., neuropathy, kidney damage)
- Many patients live well with WM for decades
Treatment of Waldenström’s macroglobulinaemia (WM)
Treatment is personalized and based on symptoms, IgM levels, and genetic profile.
Treatment options include:
Observation
- No treatment for asymptomatic patients; regular monitoring
Plasmapheresis
- Removes excess IgM to relieve hyperviscosity symptoms
Chemotherapy
- Common agents: bendamustine, cyclophosphamide
- Often combined with rituximab (anti-CD20 monoclonal antibody)
Targeted therapy
- BTK inhibitors:
- Zanubrutinib (preferred due to fewer side effects)
- Acalabrutinib, ibrutinib
- Proteasome inhibitors: bortezomib
- BCL-2 inhibitors: venetoclax (used in relapsed cases)
Stem cell transplant
- Option for younger patients with aggressive disease
Clinical trials
- Investigating radiopharmaceuticals, cancer vaccines, and novel immunotherapies
Monitoring of WM
Regular follow-up is essential to track disease progression and treatment response:
Monitoring Includes:
- IgM levels
- Blood counts
- Organ function tests
- Imaging (if needed)
- Neurological assessments (for neuropathy)
Frequency depends on disease activity—typically every 3–6 months.
Living with Waldenström’s macroglobulinaemia (WM)
WM is a chronic condition, and many patients live full lives with proper care.
Lifestyle tips
- Maintain a healthy diet and exercise routine
- Avoid infections (stay up to date with vaccinations)
- Manage fatigue with pacing and rest
- Seek support from WM-specific patient groups
Emotional wellbeing
- Coping with a rare cancer can be isolating—support networks and counseling help
- Stay informed and engaged in your care decisions
Caring for someone with Waldenström’s macroglobulinaemia (WM)
We have a range of information and resources that may help when you are caring for someone with Waldenström’s macroglobulinaemia (WM).
