Treatment Options for Waldenstrom Macroglobulinemia

How is Waldenstrom macroglobulinemia treated?

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

There are several potential treatment options for WM. Treatments are palliative, which means they’re focused on managing symptoms. Which one your healthcare team recommends can depend on several factors, such as your symptoms, age, and overall health.

Your doctor may also request certain tests to help guide your treatment, such as a bone marrow aspiration or biopsy.

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. During this time, you may still be treated for certain complications of WM, particularly thickening of the blood, called hyperviscosity.

Some people with WM are closely monitored by their healthcare team for years without needing any treatment. Studies suggest that waiting to start treatment until you show symptoms won’t affect your condition’s outlook, according to the ACS.

Targeted therapy

Targeted therapy uses drugs that focus on proteins that are either on or inside of cancer cells in order 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 protein called CD20 on cancer cells. When rituximab attaches to cancer cells, it causes their destruction.

Rituximab is often an initial part of WM treatment, even though the Food and Drug Administration (FDA) hasn’t specifically approved it for that purpose. This is a practice known as off-label use. Rituximab does have FDA approval when used along with the drug ibrutinib (Imbruvica), though.

The medication is given by infusion into a vein (IV), usually in your arm. It’s often used in combination with chemotherapy or other treatments. In fact, research published in 2019 shows that rituximab works better when you take it with chemotherapy drugs.

Other anti-CD20 drugs

If rituximab causes you severe side effects, your doctor might try another drug that targets CD20, such as ofatumumab (Arzerra) or obinutuzumab (Gazyva).

Bruton tyrosine kinase (BTK) inhibitors

There are currently three BTK inhibitor drugs used to treat WM. These drugs work by targeting a protein called BTK, which helps cancer cells grow and thrive.

These drugs are pills that you have to take once or twice each day, as directed by your doctor:

• Ibrutinib (Imbruvica). This is the first BTK inhibitor to receive FDA approval to treat WM. It may be prescribed alone or with rituximab.
• Zanubrutinib (Brukinsa). This newer drug was FDA-approved to treat WM in 2021. Clinical trials suggested that it may have less severe side effects compared to ibrutinib.
• Acalabrutinib (Calquence). This may be prescribed on its own or with other treatments. Because it is not FDA-approved to treat WM, this is an off-label use. A clinical trial examining the use of acalabrutinib for WM is currently underway.

Proteasome inhibitors

These drugs block proteins that cancer cells need to live. They can be helpful for some people with WM.

Two examples are carfilzomib (Kyprolis) and bortezomib (Velcade). Both are given by IV. However, you can also get bortezomib as a shot under the skin. Another option, ixazomib (Ninlaro) is a pill that is used alongside other treatments for WM.

mTOR inhibitors

Everolimus (Afinitor) is a pill that blocks a protein that cancer cells need to grow and divide. Your doctor may prescribe this if other treatments for WM haven’t been effective.

Chemotherapy

Chemotherapy is the use of drugs to kill rapidly dividing cells, which includes cancer cells. Unlike targeted therapy, chemotherapy has a more general effect and doesn’t seek out specific proteins on cancer cells. As such, some 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.

Immunotherapy

Immunotherapy drugs make your immune system stronger so it can better fight cancer. Doctors will sometimes prescribe immunotherapy drugs to people with WM.

You may also see these drugs referred to as immunomodulators (IMiDs). Examples include thalidomide (Thalomid) and pomalidomide (Pomalyst).

Plasmapheresis (plasma exchange)

A common complication of WM is a thickening of the blood, called hyperviscosity. This can happen due to increased levels of IgM protein in the blood and can lead to stroke and organ damage.

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

During plasmapheresis:

1. A healthcare professional places an IV line in your arm. The IV line is connected to a machine.
2. Your blood flows through the IV into the machine, where the IgM protein is removed.
3. 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 also be given a blood thinner to prevent clotting.

Other options

Stem cell transplant (bone marrow transplant)

During a stem cell transplant, diseased bone marrow is replaced with healthy blood stem cells. The goal is for these stem cells to grow into healthy bone marrow. 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. According to the ACS, the average age at diagnosis is 70 years old. In older individuals, the serious risks of a stem cell transplant can outweigh the benefits.

Blood transfusions

Some people with WM can develop a complication called anemia, which is when levels of red blood cells in the body are too low. If you develop anemia due to WM or its treatments, your doctor may recommend blood transfusions to increase red blood cell levels.

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.

Treatment considerations

As you’re presented with different treatment options for WM, there are several things to consider. Let’s explore these now.

Side effects

Each type of WM treatment has different side effects. The type of side effects that a person may experience can vary by individual and can also depend on other factors like the type of drug and dosage used.

Below, we’ll give a snapshot of the potential side effects of some of the treatment options for WM. Your healthcare team can help to give you a better idea of the types of side effects that you may experience and the strategies that you can use to help manage them.

Targeted therapy drugs

Taking rituximab can initially raise the level of IgM protein in the blood, leading to hyperviscosity. Other potential side effects can include:

• fever
• chills
• fatigue
• headaches
• nausea
• rashes

Some of the side effects of BTK inhibitors can include:

• low blood counts, which can lead to:
  • anemia
  • an increased risk of infections
  • easy bruising or bleeding
• diarrhea
• pain in the muscles and bones
• cough
• rash
• abnormal heartbeat (arrhythmia)

Proteasome inhibitors can potentially cause nerve damage, which can lead to pain and numbness in the feet and legs. This side effect typically eases once treatment is stopped. Other side effects may include:

• low blood counts
• nausea
• loss of appetite

mTOR inhibitor side effects can lead to:

• fatigue
• infections
• diarrhea
• mouth pain
• rash

Chemotherapy

In addition to cancer cells, chemotherapy can also kill other types of rapidly dividing cells in the body. These can include cells of the hair follicles, digestive tract, and bone marrow.

As a result, some of the potential side effects of chemotherapy may include:

• hair loss
• appetite loss
• nausea
• vomiting
• diarrhea
• constipation
• mouth sores
• low blood counts

Immunotherapy drugs

Immunomodulating drugs like thalidomide can cause side effects like:

• fatigue
• constipation
• nerve pain
• an increased risk of serious blood clots

The immunomodulating drugs used for WM can also lead to severe birth defects if you take them during pregnancy.

Cost of treatment

Cancer treatment can be expensive. If you need treatment for WM, don’t be afraid to talk with your doctor about the cost of your care.

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.

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

Some examples of lifestyle changes and palliative care for WM may include diet changes and relaxation techniques.

Diet changes

Cancer and its treatments may affect your appetite and cause you to lose weight. Mouth sores and nausea from chemotherapy may also make eating uncomfortable.

High calorie, high protein beverages such as milkshakes 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.

Staying hydrated

The side effects of cancer treatments can often cause dehydration. When you don’t have enough fluid in your body, you’re likely to feel more tired and weak, among other symptoms.

If you have hyperviscosity caused by WM, it’s especially important to avoid getting dehydrated.

Ways to stay hydrated include:

• drinking lots of fluids
• eating foods that have a high liquid content, like soups, fruits, and popsicles
• treating the causes of dehydration, such as fever, vomiting, and diarrhea

Getting help and support through treatment

It’s OK to feel stressed, anxious, or depressed if you or a loved one has cancer. Connecting and talking with others who are living with WM may be helpful.

Ask your doctor about support groups in your area, or visit the ACS website for a list of programs near you.

Choosing to stop treatment or choosing no treatment at all

It’s possible that treatment won’t help stop WM from growing and spreading. Additionally, WM may come back (recur) after a treatment that was initially successful. In some situations, you may not wish to receive treatment at all.

Regardless of whether you’re choosing to stop treatment or refuse treatment, it’s important to talk with your healthcare team openly and honestly about your decision. They can help give you an idea of what will happen when you don’t receive treatment.

It’s possible that they may still recommend treatments that help to address symptoms and complications like pain, hyperviscosity, and anemia. This can help you feel more comfortable.

It’s also important to discuss your decision with your loved ones. It may be a difficult conversation to have, but try your best to explain the reasons behind your decision. Remember that at the end of the day, those closest to you are there to help and support you on your journey.

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. Clinical trials aim to test new treatment regimens for cancer before they’re used on a wider scale.

Your doctor may suggest that you receive WM treatment through a clinical trial. If you’re interested in enrolling in a clinical trial, discuss this with your healthcare team.

You can also find clinical trials for WM that are supported by the National Cancer Institute here. Another central resource for finding clinical trials is ClinicalTrials.gov, run by the U.S. National Institutes of Health.

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. Treatment will be initiated if symptoms develop.

If you 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.