Waldenstrom macroglobulinemia

Overview

Waldenstrom macroglobulinemia (mak-roe-glob-u-lih-NEE-me-uh) is a rare cancer of white blood cells. It may be shortened to WM. It is a type of non-Hodgkin lymphoma called lymphoplasmacytic lymphoma (LPL). About 1,000 to 1,500 people are diagnosed with Waldenstrom macroglobulinemia each year in the United States. It accounts for about 1% of non-Hodgkin lymphomas.

In Waldenstrom macroglobulinemia, some white blood cells change and become cancer cells. These cells can build up in bone marrow, the soft tissue inside bones where blood cells are made. They can crowd out healthy blood cells. Cancer cells also may build up in lymph nodes, the spleen and other parts of the body.

Waldenstrom macroglobulinemia cells make a protein called immunoglobulin M (IgM). IgM can build up in the blood. Too much IgM can make blood too thick and slow blood flow. This can harm organs.

Waldenstrom macroglobulinemia can be serious, but it often worsens slowly. Some people do not need treatment right away. When treatment is needed, it can control symptoms and complications.

Waldenstrom macroglobulinemia and multiple myeloma

Waldenstrom macroglobulinemia and multiple myeloma are different blood cancers that occur in the bone marrow. Waldenstrom macroglobulinemia is a lymphoplasmacytic lymphoma affecting B cells and makes IgM. Multiple myeloma is a cancer of plasma cells.

Types

Symptomatic Waldenstrom macroglobulinemia

Symptomatic Waldenstrom macroglobulinemia causes symptoms or other health issues that call for treatment.

Smoldering Waldenstrom macroglobulinemia

Smoldering Waldenstrom macroglobulinemia also is called asymptomatic Waldenstrom macroglobulinemia. It means Waldenstrom macroglobulinemia is present but is not causing symptoms or organ damage that calls for treatment. People with smoldering Waldenstrom macroglobulinemia are watched closely instead of treated right away.

Causes

It's not clear what causes Waldenstrom macroglobulinemia. Cancer starts when cells have changes in their DNA. DNA gives cells instructions. Healthy cells grow and die in a controlled way. Cancer-related DNA changes can tell cells to grow too much and live too long. This can lead to a buildup of cancer cells.

In Waldenstrom macroglobulinemia, these changes happen in B cells. B cells, also called lymphoplasmacytic cells, are a type of white blood cell. The changed cells can build up in bone marrow and crowd out healthy blood cells. They also may build up in lymph nodes and the spleen.

Waldenstrom macroglobulinemia cells make a monoclonal protein called IgM. IgM can build up in the blood. This can make the blood too thick and slow its flow. This can affect organs and cause other issues.

Most gene changes in Waldenstrom macroglobulinemia cells happen randomly. They usually are not passed down from a parent. MYD88 is the most common gene change. CXCR4 is another common gene change. Family history can raise the risk of Waldenstrom macroglobulinemia. But there is no single inherited gene that explains most family cases.

Complications

Complications of Waldenstrom macroglobulinemia may include:

• Hyperviscosity syndrome. Some people with Waldenstrom macroglobulinemia develop hyperviscosity syndrome. This means extra IgM proteins in the blood make the blood too thick so it flows more slowly. Hyperviscosity syndrome can be life-threatening.
• Bing-Neel syndrome. Bing-Neel syndrome happens when Waldenstrom macroglobulinemia cells affect the brain or spinal cord. Symptoms of Bing-Neel syndrome include headaches, seizures, weakness, numbness, tingling or other nerve symptoms. The syndrome can happen when Waldenstrom macroglobulinemia is first found or later, even when it seems to be controlled.

Bing-Neel syndrome is rare. It affects about 1% of people with Waldenstrom macroglobulinemia. An MRI scan of the brain and spine and a test of spinal fluid can help diagnose Bing-Neel syndrome.

• Low blood cell counts. As Waldenstrom macroglobulinemia gets worse, it may cause low red blood cells, called anemia, and other low blood counts, such as low platelets. This can happen when cancer cells build up in the bone marrow and crowd out healthy blood cells.
• Larger than usual lymph nodes and spleen. Waldenstrom macroglobulinemia cells can build up in these organs and cause them to become enlarged.
• A switch to a more aggressive form of cancer. Some people with Waldenstrom macroglobulinemia can develop a more aggressive form of cancer called aggressive lymphoma.
• Secondary cancers. People with Waldenstrom macroglobulinemia are at a higher risk of developing other cancers. These may include thyroid cancer, kidney cancer and melanoma.
• Amyloidosis. Amyloidosis (am-uh-loi-DO-sis) is a rare condition that happens when a protein called amyloid builds up in organs. This amyloid buildup can affect the way organs work. Amyloidosis may affect the heart, kidneys and nervous system.

Treatment

Waldenstrom macroglobulinemia is not curable with current treatments. Treatment is based mainly on symptoms and complications. The goals of treatment are to ease symptoms, prevent or limit organ damage, and control the condition.

Even though the condition is not curable, many people live with it for years. Some people do not need treatment right away. When treatment is needed, it can control symptoms and complications.

Waldenstrom macroglobulinemia treatment may include watchful waiting, plasma exchange, immunotherapy, targeted therapy and chemotherapy. A bone marrow transplant, also called a stem cell transplant, may be right for some people. Your plan depends on your symptoms, test results and how fast the condition is changing. Your healthcare professional also considers your overall health and your choices.

Watch and wait

If you have smoldering Waldenstrom macroglobulinemia without symptoms or organ damage that calls for treatment, you may not need treatment right away. Instead, you might have regular blood tests to monitor your condition. Healthcare professionals sometimes call this watchful waiting. Treatment may not be needed for years. Some people with smoldering Waldenstrom macroglobulinemia never need treatment.

Watchful waiting also is called active surveillance. Follow-up often includes a review of symptoms, blood counts and IgM levels. How often you're checked depends on your risk and how quickly the condition is changing.

When treatment begins

Treatment usually starts when Waldenstrom macroglobulinemia causes symptoms or health issues. The IgM level alone usually is not a reason to start treatment. Your healthcare team looks at your symptoms and test results to decide when and what treatment is right for you.

Treatment may begin for symptoms or health issues such as:

• Anemia or other low blood counts that cause symptoms.
• Hyperviscosity syndrome.
• Enlarged lymph nodes, liver or spleen that cause symptoms.
• Moderate to severe nerve problems.
• Amyloidosis.
• Symptoms such as fever, night sweats, weight loss or severe tiredness.
• A switch to a more aggressive lymphoma.

Plasma exchange

Plasma exchange, also called plasmapheresis, removes IgM from the blood and replaces plasma with healthy plasma. It may be used if you have hyperviscosity syndrome.

Plasma exchange can lower IgM quickly and ease symptoms from thick blood. But the effect does not last. Other treatments are then used to control the cells that make IgM.

Possible side effects from plasma exchange include discomfort from IV lines and a drop in calcium that can cause tingling or muscle spasms.

Immunotherapy

Immunotherapy uses medicine to help the immune system attack cancer cells. The immune system typically finds and attacks germs and changed cells. Cancer cells can hide from the immune cells. Immunotherapy can help immune cells find and kill cancer cells.

Rituximab (Rituxan) is an immunotherapy used often for Waldenstrom macroglobulinemia. It may be combined with chemotherapy or targeted therapy. It also may be used if Waldenstrom macroglobulinemia comes back or earlier treatment does not work.

Rituximab can cause reactions during an infusion, such as chills, fever, nausea, rash, fatigue or headache.

Targeted therapy

Targeted therapy uses medicines that attack specific parts of cancer cells. Blocking these targets can cause cancer cells to die. It may be combined with immunotherapy. It also may be used if Waldenstrom macroglobulinemia doesn't respond to treatment or comes back after treatment.

Bruton tyrosine kinase (BTK) inhibitors are targeted medicines used for Waldenstrom macroglobulinemia. BTK inhibitors include ibrutinib (Imbruvica) and zanubrutinib (Brukinsa).

Pirtobrutinib (Jaypirca) is another BTK inhibitor that has shown promise in treating Waldenstrom macroglobulinemia that has come back, including after some prior BTK inhibitor treatments.

Ibrutinib can cross the blood-brain barrier, a protective layer around the brain and spinal cord, and is used to treat Bing-Neel syndrome. Zanubrutinib also is an effective treatment for Bing-Neel syndrome.

BTK inhibitors can cause diarrhea, bruising, low blood counts, bleeding, infections and heart rhythm issues. Your healthcare team can tell you whether targeted therapy is an option for you.

Chemotherapy

Chemotherapy treats cancer with strong medicines. There are many chemotherapy medicines. Most chemotherapy medicines are given through a vein. Some are taken by mouth.

Chemotherapy may be used for Waldenstrom macroglobulinemia. It often is combined with immunotherapy. It also may be used if Waldenstrom macroglobulinemia comes back or treatment doesn't work.

Chemotherapy side effects can include nausea, hair loss, mouth sores, diarrhea or constipation, and low blood counts. Some chemotherapy medicines also can damage nerves or the heart.

Bone marrow transplant

A bone marrow transplant, also called a stem cell transplant, may be an option for some people if treatment doesn't work or Waldenstrom macroglobulinemia comes back.

A bone marrow transplant puts healthy blood-forming stem cells into the body after treatment. The cells can come from your own body. This is called an autologous stem cell transplant. They also can come from a donor. This is called an allogeneic stem cell transplant.

Chemotherapy usually is given before the transplant. The high-dose treatment used with a stem cell transplant can cause serious, sometimes life-threatening side effects.

Monitoring after treatment

After treatment, you'll likely have regular follow-up visits to check for signs that Waldenstrom macroglobulinemia has come back. This is called a relapse. Blood tests can help check for relapse.

Follow-up may include a complete blood count, an IgM test and serum protein electrophoresis. You may have kidney and liver tests. Your healthcare team also checks for new or returning symptoms. The schedule depends on your condition and the treatment you had.

Preparing for an appointment

Make an appointment with a healthcare professional if you have any symptoms that worry you. If your healthcare team thinks that you may have Waldenstrom macroglobulinemia, you'll likely see a doctor who treats blood and bone marrow conditions, called a hematologist.

Here's some information to help you get ready for your appointment.

What you can do

Ask if you need to do anything before the appointment. For example, you may need to change what you eat or drink before a test.

Bring a person you trust, such as a family member or friend, if you can. It can be hard to remember everything you hear during an appointment. Another person may help you remember key details.

Before your appointment, make a list of:

• Symptoms you're having, even if some don't seem related to the reason for your visit.
• Major stresses, recent life changes and other important personal information.
• All medicines, vitamins, herbs and other supplements you're taking, and the doses.
• Questions to ask your healthcare professional.

Basic questions may include:

• Do I have Waldenstrom macroglobulinemia?
• What is my risk group?
• Will I need more tests?
• What are the treatment options?
• How does each treatment affect my survival?
• What are the potential side effects of each treatment?
• How will each treatment affect my daily life?
• Which treatment option is the right choice for me, and why?
• Should I see a specialist?
• Are there any brochures or other printed material that I can take? What websites do you suggest?
• What will decide whether I should plan for a follow-up visit?

Feel free to ask other questions during your appointment.

What to expect from your doctor

Your healthcare professional may ask you questions, such as:

• When did your symptoms begin?
• Do your symptoms happen all the time or do they come and go?
• How do your symptoms affect your daily life?
• What, if anything, seems to make symptoms better?
• What, if anything, seems to make symptoms worse?
• Have you had fevers, night sweats or weight loss?
• Have you noticed any lumps, swelling or pain anywhere in your body?
• Do you have other medical conditions?
• Has anyone in your family had lymphoma?
• What are your biggest worries about your diagnosis or treatment?

Be ready to answer questions so that you have time to talk about what's most important to you.

Survival rates

Survival rates show how many people in a group are alive after a set number of years. For example, a five-year survival rate is the percentage of people alive five years after diagnosis. Survival statistics describe groups. They cannot tell exactly how long one person will live.

Survival statistics

The estimated five-year overall survival rates based on the MSS-WM for a test group were:

• Low risk: about 93%.
• Low-intermediate risk: about 90%.
• Intermediate risk: about 75%.
• High risk: about 57%.

The estimated 10-year overall survival rates in the same group were:

• Low risk: about 91%.
• Low-intermediate risk: about 80%.
• Intermediate risk: about 64%.
• High risk: about 35%.

Severe Waldenstrom macroglobulinemia or its complications can be life-threatening. The exact cause of death varies from person to person. In people older than 65, the most common cause of death is not cancer related.

Outlook

For active or symptomatic Waldenstrom macroglobulinemia, the Modified Staging System for Waldenstrom Macroglobulinemia (MSS-WM) uses age and two blood tests, albumin and lactate dehydrogenase (LDH), to estimate risk group and outlook. People in lower risk groups usually live longer than people in higher risk groups.

MSS-WM groups help healthcare professionals talk about outlook. A risk group cannot predict exactly how long you will live. Survival with Waldenstrom macroglobulinemia has improved over time, but each person's outlook is different.

Life expectancy with Waldenstrom macroglobulinemia varies widely. One recent review found a median survival of more than 10 years for people diagnosed before age 70. Median survival was about seven years for people ages 70 to 79 and about four years for people age 80 or older. Median survival is the length of time at which half of the people in a group are still living.

These numbers describe groups, not what will happen to one person. Age has a strong effect on survival.

Some people with Waldenstrom macroglobulinemia live for many years after diagnosis. Long-term survival depends on age, how the condition is affecting you, complications and how well the cancer responds to treatment.

Group statistics cannot predict whether one person will live 20 years or longer. Some people do live for many years after diagnosis, but individual outlook varies.

Survival statistics take years to collect. The latest numbers include people who were treated more than five years ago. Some of them did not have access to today's newer treatments. But survival rates are improving.

What you can do

Ask your healthcare team what the survival numbers mean for you. Keep follow-up visits and report new or changing symptoms so your healthcare team can watch your condition and decide when treatment may be needed.