Waldenström macroglobulinemia: Full guide

What is Waldenström macroglobulinemia?

Waldenström macroglobulinemia (often called WM or Waldenström) is a rare, slow-growing blood cancer. It is a type of non-Hodgkin lymphoma. It starts in B cells, a kind of white blood cell that helps fight infection. The cancer cells are a mix of lymphocytes and plasma cells, so doctors sometimes call it lymphoplasmacytic lymphoma.

The cancer cells live mostly in the bone marrow. Bone marrow is the soft, spongy tissue inside your bones where blood cells are made. The cells make large amounts of one antibody protein called IgM. Too much IgM can make the blood thick. Thick blood flows slowly and can cause headaches, blurry vision, nosebleeds, or confusion. This is called hyperviscosity.

The cancer cells can also crowd out healthy blood cells. This can cause anemia (low red blood cells), which makes people feel tired and short of breath. Some people have swollen lymph nodes, a large spleen, night sweats, or weight loss. In some people, the IgM protein attacks the nerves and causes numbness or tingling in the feet and hands.

WM is most common in people in their 60s and 70s, and it is more common in men and in White Americans. It sometimes runs in families. WM usually cannot be cured, but it often grows slowly. Many people live for many years, and some never need treatment.

Types and related conditions

IgM MGUS

A common early condition where a blood test finds a small amount of IgM protein, but there are few or no cancer cells in the marrow and no symptoms. It does not need treatment. A small number of people with IgM MGUS go on to develop WM, so your care team checks your blood from time to time.

Smoldering (asymptomatic) WM

WM cells are in the bone marrow, but there are no symptoms or problems that need treatment. Most people are watched closely with regular blood tests. Some people stay in this stage for many years.

Symptomatic WM

WM that is causing problems, such as anemia, thick blood, swollen lymph nodes, nerve damage, or tiredness that affects daily life. This is when treatment usually starts.

Hyperviscosity syndrome

When high IgM makes the blood too thick. It can cause bleeding from the nose or gums, blurry vision, headaches, dizziness, or confusion. It needs fast treatment.

IgM-related nerve damage (neuropathy)

The IgM protein can attack the coating of the nerves, often a part called MAG. This causes slow, building numbness, tingling, or unsteady walking, usually starting in the feet. It can happen even when the amount of IgM is small.

Cryoglobulinemia and cold agglutinin disease

In some people, the IgM protein clumps or attacks red blood cells in the cold. This can cause painful, blue, or purple fingers and toes, skin sores, or anemia. Keeping warm helps, and treatment of the WM may be needed.

AL amyloidosis

Rarely, pieces of the abnormal protein build up in organs like the heart, kidneys, or nerves. This needs special tests and treatment.

Bing-Neel syndrome

A rare problem where WM cells spread to the brain or spinal cord. It can cause headaches, confusion, trouble walking, or vision changes. It is found with an MRI and a spinal tap.

Tests you may have

Serum protein electrophoresis (SPEP) and immunofixation

Blood tests that find the abnormal protein and show it is IgM. The amount of this protein, called the M-spike, helps your care team track the disease over time.

Quantitative IgM level

A blood test that measures the total IgM. It is checked often, because it rises and falls with the disease and treatment.

Serum viscosity

A blood test that measures how thick your blood is. It is done if your IgM is high or you have symptoms like nosebleeds, headaches, or blurry vision.

Eye exam

An eye doctor looks at the back of your eyes. Thick blood can cause swollen veins and small bleeds there. This exam helps decide how urgent treatment is.

Blood counts and chemistry

A complete blood count checks for anemia and low platelets. Other tests check your kidneys, liver, beta-2 microglobulin, albumin, and LDH. Some of these help show your risk group.

Bone marrow biopsy

A needle takes a small sample of marrow, usually from the back of the hip bone. You get numbing medicine first. The sample confirms the diagnosis and is used for gene tests.

CT scan

A scan of the chest, belly, and pelvis looks for swollen lymph nodes or a large spleen. A PET scan is used only in some cases.

Nerve tests

If you have numbness or tingling, you may have a blood test for anti-MAG antibodies and a nerve study (EMG) to check how your nerves work.

Other blood tests

Depending on your symptoms, tests may check for cryoglobulins, cold agglutinins, hepatitis B and C, or amyloidosis. Hepatitis B testing is done before rituximab.

Risk groups and when to treat

WM is not staged like many other cancers, by tumor size or spread. Instead, doctors ask two questions. First, does the WM need treatment now? Second, what is the risk group?

Treatment is usually started only when WM causes problems. Having a high IgM level by itself, without symptoms, is usually not a reason to start treatment. Many people stay on watch and wait for years.

Doctors use a scoring system called the IPSSWM, or a newer version called the revised IPSSWM. It uses your age and blood tests like beta-2 microglobulin, albumin, and LDH. The score helps your care team understand how the disease may act. It does not decide your whole future.

Signs that treatment is needed

Anemia or low platelets from WM, thick blood (hyperviscosity), large or painful lymph nodes or spleen, fevers, night sweats, weight loss, nerve damage from IgM, cryoglobulinemia, cold agglutinin disease, or amyloidosis.

Watch and wait

If none of these problems are present, you have regular visits and blood tests instead of treatment. Starting treatment early has not been shown to help people live longer.

Low-risk group

Fewer of the risk factors in the scoring system. These people tend to do very well for a long time.

Intermediate-risk group

Some of the risk factors. This is a common group.

High-risk group

More risk factors, such as older age, high beta-2 microglobulin, high LDH, or low albumin. The WM may need closer follow-up.

Gene tests and lab markers

Gene tests on your bone marrow sample can confirm the diagnosis and help guide treatment. The most important ones look at two genes called MYD88 and CXCR4.

These results can help your care team choose between medicine types and predict how fast and how well a medicine may work. Ask your care team which changes your WM has.

MYD88 L265P

A gene change found in more than 9 out of 10 people with WM. It helps confirm the diagnosis. WM with this change usually responds well to BTK inhibitor pills.

MYD88 wild-type (no MYD88 change)

A small group of people do not have the MYD88 change. Their WM may respond less well to some BTK inhibitors, and doctors may choose a different treatment, such as an antibody and chemotherapy combination.

CXCR4 mutations

Gene changes found in about 3 out of 10 people with WM. With these changes, BTK inhibitors still work, but responses may be slower and less deep. Your care team may consider this when choosing treatment.

TP53 changes

A less common gene change that can mean the WM may be harder to control. It may affect which treatment is chosen.

IgM level

The main protein marker followed over time. It usually drops with treatment. Rituximab can cause a short-term rise called an IgM flare.

Hemoglobin

The red blood cell level. A rise in hemoglobin is one of the best signs that treatment is helping.

Anti-MAG antibodies

A blood test that helps explain nerve damage caused by IgM.

Main treatments

Watch and wait

If WM is not causing problems, the safest plan is usually close follow-up with regular visits and blood tests. Treatment starts when it is needed.

Plasmapheresis (plasma exchange)

For thick blood, a machine filters IgM out of your blood. It works quickly to ease symptoms, but it does not treat the cancer cells, so other treatment follows. It may also be done before rituximab if IgM is very high.

BTK inhibitor pills

These pills block a signal WM cells need to grow. Examples are zanubrutinib, ibrutinib, and acalabrutinib. They are taken every day, usually for as long as they keep working. Zanubrutinib is often chosen because it causes fewer heart rhythm problems than ibrutinib. Pirtobrutinib, a newer type of BTK inhibitor, may be used if the WM grows on another one.

Bendamustine with rituximab (BR)

A chemotherapy drug (bendamustine) given with an antibody (rituximab) by IV for about 6 months. It is a fixed-length treatment, so you get a break from treatment afterward. It often controls WM for many years.

Other antibody combinations

Rituximab can be combined with cyclophosphamide and dexamethasone (DRC), or with bortezomib and dexamethasone (BDR). Rituximab alone may be used for milder disease or nerve damage. If IgM is very high, rituximab may be held at first, because it can make IgM rise for a short time.

Choosing a first treatment

There is no single best choice for everyone. Your care team weighs your gene results, other health problems, and whether you prefer daily pills that are taken long term or a treatment with a set end date.

Treatment if WM comes back

WM often comes back after some years. Options include repeating a treatment that worked well before, switching to a BTK inhibitor or a different antibody combination, or other drugs such as bortezomib or venetoclax.

Stem cell transplant

Rarely used, but it may be an option for some younger people whose WM keeps coming back after several treatments.

Clinical trials

Studies are testing newer drugs, such as BCL2 inhibitors, BTK degraders, and immune treatments. Ask your care team whether a trial fits you.

Common side effects and what helps

Heart rhythm problems

BTK inhibitors, especially ibrutinib, can cause an irregular heartbeat called atrial fibrillation. They can also raise blood pressure. Your care team will check your pulse and blood pressure often. Call if you feel your heart racing or fluttering.

Bleeding and bruising

BTK inhibitors make bruising and bleeding easier. Tell your care team before any surgery or dental work, because the pill may need to be paused. Ask before taking blood thinners, aspirin, or fish oil.

Diarrhea, joint aches, and muscle cramps

These are common with BTK inhibitors and often get better over time. Drink fluids, and tell your care team if they bother you. Dose changes can help.

Infections

WM and its treatments weaken the immune system. You may take medicines to prevent shingles or pneumonia. Stay up to date on flu, COVID, and pneumonia vaccines. Live vaccines are usually avoided.

Low blood counts

Chemotherapy can lower white cells, red cells, and platelets. Your care team checks your counts and may adjust the dose or timing.

Infusion reactions and IgM flare

Rituximab can cause chills, fever, or itching during the first infusions. Medicines before the infusion help. Rituximab can also make IgM rise for a short time, so your care team will watch for thick blood.

Rash and tiredness from bendamustine

Bendamustine can cause rash, nausea, and tiredness. Nausea medicine and rest help. It also lowers some immune cells for a long time, so preventing infections is important.

Numbness or tingling (neuropathy)

Nerve problems can come from the IgM protein or from bortezomib. Report new or worse numbness early. Your care team can change the dose or schedule before it gets worse. Balance exercises and safe shoes help prevent falls.

Hepatitis B coming back

Rituximab can wake up a past hepatitis B infection. You will be tested first, and some people take an antiviral medicine to prevent it.

Living with Waldenström macroglobulinemia

For most people, WM is a long-term condition managed over many years, a bit like other chronic illnesses. There are often long stretches with no treatment at all. Many people keep working, traveling, and doing the things they enjoy.

Learn the signs of thick blood: nosebleeds, bleeding gums, blurry vision, headaches, dizziness, or confusion. Call your care team right away if they happen. Tell any hospital or doctor that you have WM, especially before a blood transfusion, because a transfusion can make thick blood worse. Keep warm in cold weather if your IgM reacts to cold. Protect your feet and use good lighting at home if you have numbness, to lower the risk of falls.

If you take a BTK inhibitor, keep a list of all your medicines and supplements. Some drugs, herbs, and grapefruit can change how these pills work. Tell every doctor and dentist you take one, and ask before stopping it for a procedure.

Feelings of worry while waiting for treatment are normal. Some people call watch and wait "watch and worry." Talking with your care team, a counselor, or other people with WM can help. The International Waldenström's Macroglobulinemia Foundation (IWMF) and Blood Cancer United (formerly the Leukemia and Lymphoma Society) offer free support and education.