Treating Waldenström's macroglobulinemia

Defining your patient's treatment plan

Find out what your next steps should be in planning your patient’s treatment

Defining your patient's treatment plan

The history of WM: from first definition to current advances and expectations for the future

From the first description in 1944 by the Swedish hematologist Jan Waldenström, to the evolutions in management and treatment, with a look to possible future developments.

CP-299792, approved on 11/05/2022

Indications for treatment initiation in patients with WM[1]


These clinical symptoms are indications treatment should be initiated in your patient:

  • Recurrent fever, night sweats, weight loss, fatigue
  • Hyperviscosity
  • Lympthadenopathy: either symptomatic or bulky (maximum diameter of at least 5 cm)
  • Symptomatic hepatomegaly and/or splenomegaly
  • Symptomatic organomegaly and/or organ or tissue infiltration
  • Peripheral neuropathy due to WM

If your patient displays the following laboratory findings, treatment should be initiated:

  • Symptomatic cryoglobulinaemia
  • Symptomatic cold agglutinin anaemia
  • Autoimmune haemolytic anaemia and/or thrombocytopaenia
  • Nephropathy related to WM
  • Amyloidosis related to WM
  • Hb ≤10 g/dL
  • Platelets <100x109/L
  • IgM levels >60 g/L

The ESMO guidelines for the management of WM outline clinical and laboratory indications for treatment initation.[1]

To treat or not to treat?

Patients with low Hb levels, high lymphoplasmacytic cell infiltration, IgM flare and high ß2-microglobulin levels may be at higher risk for development of symptomatic WM.[2][3]

However, patients may be asymptomatic for 5–10 years and can be managed with a ‘watch and wait’ approach, without treatment and should be followed up every 3-6 months.[1][2][3]

No data exist to support early initiation of therapy over a watch and wait strategy, nor is the level of monoclonal IgM alone an indication to start treatment.[1]

Hyperviscosity is a clinical emergency. Plasmapheresis should be used immediately in patients with symptomatic hyperviscosity, in addition to appropriate systemic therapy for WM.[1]

Additional tests

Additional work-up is often based on symptomatic presentation and laboratory findings that can indicate the need for treatment initiation.[4]

Clinically-indicated diagnostic work-up[4]

Symptom / clinical presentation
Symptom / clinical presentation

Hyperviscosity syndrome - headaches, visual
disturbances, confusion, epistaxis


• Cryoglobulins
• Cold agglutinine titre
• Serum viscosity

Symptom / clinical presentation
Anaemia with haemolysis
• Coombs testing
• Cold agglutinine titre
Symptom / clinical presentation
Raynaud-like symptoms, acrocyanosis, ulcerations
of the extremities

• Cryoglobulins

Symptom / clinical presentation

• Screening for acquired von Willebrand disease

Symptom / clinical presentation

• Myelin-associated glycoprotein (anti-MAGs)
• Specialist neurologocal evaluation

Symptom / clinical presentation
• Fat aspirate stained with Congo red
• Cardiac and renal biomarkers

Types of WM treatment

For asymptomatic patients with acceptable IgM blood levels, no treatment is required. These patients will be monitored and seen by their clinic every 3–6 months for review.[5]

This course of action may seem confusing at first, but as there is no evidence that treating early in asymptomatic patients is beneficial, ‘watch and wait’ is applied in order to maintain the patient’s quality of life.[5]

Treatment will begin if the patient:[5]

  • Develops WM-related symptoms
  • Has elevated levels of IgM protein in the blood or they experience hyperviscosity
  • Experiences changes in blood count (e.g. anaemia)
  • Develops other complications (e.g. progressive neuropathy, cryoglobulinaemia or cold agglutinin disease)

Treatment may be required to treat WM symptoms and side effects of WM treatment, which include:[6]

  • Plasmapheresis, when a patient has high levels of IgM resulting in hyperviscosity
  • Blood transfusions or platelet transfusions to combat low blood or low platelet counts
  • Immunoglobulin replacement therapy, for patients with low antibody levels
  • Antibiotics or antiviral drugs, to prevent infections

There are a range of different treatment options for WM patients[5][^6]:

  • Chemotherapy, given orally, intravenously or subcutaneously
  • Steroids, often used in conjunction with chemotherapy
  • Monoclonal antibody therapy
  • Biological therapies
  • Stem cell transplantation
  • CAR T-cell therapy

Treatment selection should then be directed by the overall health of your patient, tumour burden, and clinical presentation.[1] Guideline therapy recommendations should be considered in conjunction with local practices and available treatment options.

Follow-up after WM treatment

Patients are monitored every 3–6 months after finishing treatment, possibly requiring further tests to assess their disease state. If they relapse from WM remission, depending on the response to their first-line treatment, this could be repeated, or they can be put in a second-line of treatment.[6]

Learn about the steps involved in diagnosing your patients’ WM
Find out more about discussing WM with your patients

Download this information on treating Waldenström’s macroglobulinemia

CAR T-cell=chimeric antigen receptor T-cell; ESMO=European Society for Medical Oncology; IgM=immunoglobulin M; Hb=haemoglobin; WM=Waldenström’s macroglobulinemia.

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CP-343204 - September 2022