Treatment Options for Waldenstrom Macroglobulinemia


Waldenstrom macroglobulinemia (WM) is a rare, slow-growing type of non-Hodgkin’s lymphoma (blood cancer). People with this cancer have high levels of white blood cells and an abnormal protein called monoclonal immunoglobulin M (IgM) in their bone marrow.

There’s no cure for WM, but many different treatments are available to help manage symptoms and prevent complications.

Different types of doctors may provide care for you during your treatment journey with WM. Your healthcare team may include doctors who specialize in treating cancer (oncologists) and doctors who treat blood and bone marrow disorders (hematologists), among others.

Watchful waiting

If blood tests show signs of WM, but you don’t have any symptoms, you may not need treatment. Instead, your doctor may suggest regular visits and blood tests. This is called watchful waiting, or monitoring.

Watchful waiting for WM includes doctor’s visits and blood tests about every 1 to 2 months.

Some people with this type of blood cancer are closely monitored by doctors for years without needing any treatment. Studies suggest that waiting to start treatment until you show symptoms won’t affect your outlook, according to the American Cancer Society.

Targeted therapy

Targeted therapy uses drugs that focus on proteins or other substances of cancer cells to stop them from growing. Unlike chemotherapy, it spares healthy cells. Common types of targeted therapy for WM include:

Rituximab (Rituxan). This drug targets a substance of cancer cells called CD20. It kills cancer cells and makes remaining ones more likely to be destroyed by chemotherapy.

Rituximab is often the first drug used to treat WM, even though the Food and Drug Administration (FDA) hasn’t specifically approved it for that purpose. This practice is known as “off-label” use. It does have FDA approval when used in combination with the drug ibrutinib (Imbruvica).

The medication is given by infusion into a vein (IV), usually in your arm. Your doctor may prescribe it alone or with chemotherapy drugs. Research shows that rituximab works better when you take it with chemotherapy drugs. Taking it by itself (monotherapy) can cause IgM levels to rise, making your blood thick.

Side effects include fever, headaches, upset stomach, rashes, and fatigue.

Other anti-CD20 drugs. If rituximab causes you severe side effects, your doctor might try another drug that targets CD20, such as:

  • ofatumumab (Arzerra)
  • obinutuzumab (Gazyva)
  • rituximab-abbs (Truxima)

Bruton tyrosine kinase (BTK) inhibitors. Ibrutinib (Imbruvica) is specifically approved by the FDA to treat WM. It targets a protein called Bruton’s tyrosine kinase (BTK), which helps cancer cells grow. Ibrutinib is a pill you take once a day. Your doctor may prescribe it alone or with rituximab.

Zanubrutinib (Brukinsa) is a newer BTK inhibitor. It’s also FDA-approved to treat WM. Clinical trials suggested that it may have less severe side effects compared to ibrutinib.

Side effects of these drugs include low red and white blood cell counts, changes in heartbeat (arrhythmia), diarrhea, constipation, upset stomach, and infection.

Proteasome inhibitors. These drugs block proteins that cancer cells need to live. They’re used to treat multiple myeloma, but they can help some people with WM, too.

Two examples are carfilzomib (Kyprolis) and bortezomib (Velcade). Both are given by infusion through a vein. However, bortezomib also can be given as a shot under the skin.

Side effects include low blood counts, nausea, and pain and numbness in the feet and legs due to nerve damage.

mTOR inhibitors. Everolimus (Afinitor) is a pill that blocks a protein cells need to grow and divide. Your doctor may prescribe this if other targeted medications for WM don’t work.

Side effects include infections, rash, diarrhea, mouth pain, and fatigue.


Chemotherapy is the use of drugs to kill cancer cells. Unlike targeted treatment, chemotherapy doesn’t seek out specific substances on cancer cells. So healthy cells are often killed during chemotherapy, too.

Chemotherapy drugs that have been used to treat WM include:

  • bendamustine (Treanda)
  • cladribine (Leustatin)
  • cyclophosphamide (Cytoxan)
  • doxorubicin (Adriamycin)
  • fludarabine (Fludara)
  • vincristine (Oncovin)

Your doctor may give you a combination of chemotherapy drugs, or prescribe them with a targeted treatment such as rituximab.

If you’re getting a bone marrow (stem cell) transplant, you may receive high- dose chemotherapy first.

Chemotherapy can cause a dangerous drop in white blood cell levels, which may lead to bleeding, bruising, and raise your risk of infection. Other common side effects of chemotherapy include:

  • hair loss
  • fatigue
  • mouth sores
  • nausea
  • vomiting


Immunotherapy drugs make your immune system stronger so it can better fight off cancer. They’re often used to treat multiple myeloma, but doctors sometimes prescribe them to people with WM, too. Immunotherapy drugs are also called immunomodulators (IMiDs). Examples include:

  • thalidomide (Thalomid)
  • pomalidomide (Pomalyst)

Severe birth defects can occur if you take these drugs during pregnancy.

Other options

Blood filtering (plasma exchange, or plasmapheresis). A common complication of WM is thickening of the blood (hyperviscosity), which can lead to stroke and organ damage.

If you have symptoms of this complication, you’ll need treatment to filter your blood and reverse symptoms. This blood-filtering treatment is called plasma exchange, or plasmapheresis.

During plasmapheresis, a healthcare provider places an IV line in a vein in your arm and connects it to a machine. Your blood flows through the IV into the machine, where the IgM protein is removed. The healthy blood flows back from the machine into your body through another IV line.

Plasmapheresis takes a few hours. You can lie down or recline in a chair. You may be given a blood thinner to prevent clotting.

Stem cell transplant (bone marrow transplant). During a stem cell transplant, diseased bone marrow is replaced with healthy blood stem cells. Stem cells help healthy bone marrow grow. High-dose chemotherapy is usually given first to clear out the existing bone marrow.

If you’re a younger adult with WM and other treatments haven’t worked, your doctor might suggest a stem cell transplant. However, stem cell transplantation isn’t a common treatment for WM. Most people with this rare blood cancer are over age 60, and the serious risks of transplant outweigh the benefits.

Spleen removal (splenectomy). If your blood cancer is causing a painful, swollen spleen and medication hasn’t helped, your doctor may suggest removing it. However, this isn’t a common treatment for WM.

Cost of treatment

Cancer treatment can be expensive. If you need treatment for WM, don’t be afraid to talk to your doctor about the cost of your care. Talking about cost is an important part of high-quality cancer care, according to the American Society of Clinical Oncology (ASCO).

Your doctor may be able to offer cost-saving tips or recommend ways to get financial aid. If you have health insurance, it’s always a good idea to check with your insurer before treatment to determine what’s covered. It may be challenging to understand what’s covered by your health insurance.

If you can’t afford treatment, consider contacting the drug manufacturer. Some companies offer assistance programs to help cut costs.

Lifestyle tips

If you’re receiving treatment for WM, your doctor may also recommend lifestyle changes to help you feel better and improve your quality of life. Sometimes this is called palliative care. Palliative care is any treatment that helps:

  • ease your symptoms and treatment side effects
  • improve your quality of life
  • support you and your family during your cancer journey

Lifestyle changes and palliative care for WM may include:

  • Diet changes. Cancer and it’s treatments may affect your appetite and cause you to lose weight. Mouth sores and nausea from chemotherapy may make eating uncomfortable. High-calorie, high-protein beverages such as milk shakes and canned liquid supplements can provide important nutrients and restore energy. If you’re unable to eat big meals, try eating small protein-rich snacks throughout the day, such as yogurt, cereal, or cheese and crackers. Avoid crunchy and acidic foods that can irritate a sore mouth.
  • Relaxation techniques. Relaxing activities and exercises such as yoga and tai chi can help soothe stress and manage cancer pain. Even taking a few deep breaths to quiet your mind can reduce tension, improve sleep, and make some treatments work better.
  • Emotional support. It’s normal to feel stressed, anxious, or depressed if you or a loved one has cancer. Connecting with and talking to others who are living with WM may be helpful. Ask your doctor about support groups in your area, or visit the American Cancer Society website for a list of programs near you.

Are we close to a cure?

There’s no cure for WM, but researchers are actively studying new ways to treat it. Several new drugs and drug combinations are currently in clinical trials.

If you have signs and symptoms of WM and approved treatments have not worked for you, ask your doctor if a clinical trial is an option. Clinical trials allow you to get access to newer treatments.

The takeaway

If a blood test shows you have signs of WM, but you don’t have symptoms, you won’t need medications or other treatments. Your doctor will likely suggest regular checkups and blood tests.

If you have do have symptoms of WM, starting treatment right away can make you feel better, prevent complications, and help you live longer. Chemotherapy is usually given with targeted drug treatments.

Most people with this rare blood cancer will have the disease come back after the first treatment. However, you and your doctor have many options to choose from if this occurs.

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