Waldenstrom Macroglobulinemia (Lymphoplasmacytic Lymphoma): Types of Treatment

Approved by the Cancer.Net Editorial Board, 03/2022

ON THIS PAGE: You will learn about the different types of treatments doctors use for people with Waldenstrom macroglobulinemia. Use the menu to see other pages.

This section explains the types of treatments, also known as therapies, that are the standard of care for Waldenstrom macroglobulinemia. “Standard of care” means the best treatments known. When making treatment plan decisions, you are encouraged to discuss with your doctor whether clinical trials are an option. A clinical trial is a research study that tests a new approach to treatment. Doctors learn through clinical trials whether a new treatment is safe, effective, and possibly better than the standard treatment. Clinical trials can test a new drug, a new combination of standard treatments, or new doses of standard drugs or other treatments. Clinical trials are an option for all stages of cancer. Your doctor can help you consider all your treatment options. Learn more about clinical trials in the About Clinical Trials and Latest Research sections of this guide.

How Waldenstrom macroglobulinemia is treated

In cancer care, different types of doctors often work together to create a patient’s overall treatment plan that combines different types of treatments. This is called a multidisciplinary team. Cancer care teams include a variety of other health care professionals, such as physician assistants, nurse practitioners, oncology nurses, social workers, pharmacists, counselors, dietitians, and others.

Treatment options and recommendations depend on several factors, including the type and stage of cancer, possible side effects, and the patient’s preferences and overall health. Take time to learn about all of your treatment options and be sure to ask questions about things that are unclear. Also, talk about the goals of each treatment with your doctor and what you can expect while receiving the treatment. These types of talks are called "shared decision-making." Shared decision-making is when you and your doctors work together to choose treatments that fit the goals of your care. Shared decision-making is particularly important for Waldenstrom macroglobulinemia because there are different treatment options. Learn more about making treatment decisions.

The common types of treatments used for Waldenstrom macroglobulinemia are described below. Your care plan also includes treatment for symptoms and side effects, an important part of cancer care.

Watchful waiting

Some people with Waldenstrom macroglobulinemia may not need immediate treatment if they are otherwise healthy and the disease is not causing any symptoms or problems. In these situations, patients are closely monitored, and active treatment begins if symptoms develop or the immunoglobulin M (IgM) level increases. This approach may be called watchful waiting, watch-and-wait, or active surveillance. There is very good evidence that, in some people with low-grade lymphoma, watchful waiting does not affect the chances of survival as long as the patient receives regular and careful follow-up. Sometimes, treatment can be delayed for many months or even years.

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Plasma exchange

Plasma exchange, also called plasmapheresis, is used to reduce the thickness of the blood. It is done to help relieve the symptoms of hyperviscosity in people with Waldenstrom macroglobulinemia caused by an elevated IgM level. Caring for a person's symptoms and side effects is an important part of the overall cancer treatment plan.

During this procedure, blood is taken from a vein, and plasma is removed from the body after it is separated from the red and white blood cells. Plasma is the liquid part of the blood. The blood cells are then mixed with a plasma substitute, usually an albumin solution, and returned to the patient. A plasma exchange is usually done using a blood cell separator. This treatment is generally used as a temporary treatment until a person receives treatment with medication (see below), which can provide control of IgM proteins over a longer time.

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Therapies using medication

The treatment plan may include medications to destroy cancer cells. Medication may be given through the bloodstream to reach cancer cells throughout the body. When a drug is given this way, it is called systemic therapy. Medication may also be given locally, which is when the medication is applied directly to the cancer or kept in a single part of the body.

This treatment is generally prescribed by a medical oncologist, a doctor who specializes in treating cancer with medication.

Medications are often given through an intravenous (IV) tube placed into a vein using a needle or as a pill or capsule that is swallowed (orally). If you are given oral medications, be sure to ask your health care team about how to safely store and handle them.

The types of medications used for Waldenstrom macroglobulinemia include:

  • Chemotherapy

  • Targeted therapy

Each of these types of therapies is discussed below in more detail. A person may receive 1 type of medication at a time or a combination of medications given at the same time.

The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications prescribed for you, their purpose, and their potential side effects or interactions with other medications.

It is also important to let your doctor know if you are taking any other prescription or over-the-counter medications or supplements. Herbs, supplements, and other drugs can interact with cancer medications, causing unwanted side effects or reduced effectiveness. Learn more about your prescriptions by using searchable drug databases.

Chemotherapy

Chemotherapy is the use of drugs to destroy cancer cells, usually by keeping the cancer cells from growing, dividing, and making more cells.

A chemotherapy regimen, or schedule, usually consists of a specific number of cycles given over a set period of time. A patient may receive 1 drug at a time or a combination of different drugs given at the same time. Common drugs for treating Waldenstrom macroglobulinemia that is causing symptoms or is growing or spreading include:

  • Bendamustine (Treanda), which is used to treat Waldenstrom macroglobulinemia when it is first diagnosed or when it returns

  • Cyclophosphamide (available as a generic drug)

  • Fludarabine (Fludara)

Sometimes, cladribine (Leustatin) or chlorambucil (Leukeran) may also be used.

The side effects of chemotherapy depend on the individual, the type of drug and the dose used, but they can include fatigue, risk of infection, nausea and vomiting, loss of appetite, and diarrhea. These side effects usually go away after treatment is finished.

Learn more about the basics of chemotherapy.

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Targeted therapy

Targeted therapy is a treatment that targets the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. This type of treatment blocks the growth and spread of cancer cells and limits damage to healthy cells.

Not all tumors have the same targets. To find the most effective treatment, your doctor may run tests to identify the genes, proteins, and other factors in your tumor. This helps doctors better match each patient with the most effective treatment whenever possible. In addition, research studies continue to find out more about specific molecular targets and new treatments directed at them. Learn more about the basics of targeted treatments.

Targeted therapy for Waldenstrom macroglobulinemia includes monoclonal antibodies. A monoclonal antibody is a type of targeted therapy. It is directed against a specific protein in the cancer cells, and it does not affect cells that do not have that protein. Rituximab (Rituxan) is a monoclonal antibody used to treat many different types of B-cell lymphoma.

Rituximab works by targeting a molecule on the surface of cells called CD20. When the antibody attaches to CD20, some lymphoma cells die and others appear to become more susceptible to chemotherapy. Rituximab can be used either alone or in combination with chemotherapy for people with Waldenstrom macroglobulinemia. Although it is effective by itself, there is increasing evidence that rituximab works better when combined with chemotherapy to treat many types of B-cell lymphomas.

Other anti-CD20 antibodies work in similar ways and include obinutuzumab (Gazyva), ofatumumab (Arzerra), and rituximab-abbs (Truxima).

Ibrutinib (Imbruvica) and zanubrutinib (Brukinsa) are a type of targeted therapy called a kinase inhibitor. These drugs target Bruton’s tyrosine kinase (BTK) proteins in cancerous B cells and are approved to treat Waldenstrom macroglobulinemia. Bortezomib (Velcade) is another type of targeted therapy called a proteasome inhibitor, targeting specific enzymes called proteasomes that digest proteins in the cells.

Talk with your doctor about possible side effects for each targeted therapy and how they can be managed.

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Bone marrow transplantation/stem cell transplantation

A stem cell transplantation is a medical procedure in which specialized cells, called hematopoietic stem cells, are collected from the blood circulating through the body, called peripheral blood, so they may develop into healthy bone marrow. Hematopoietic stem cells are blood-forming cells found both in the bloodstream and in the bone marrow. Sometimes, the stem cells are collected from bone marrow, so the procedure may also be called a bone marrow transplantation. You may also hear this procedure called a hematopoietic stem cell transplant.

Transplantation is only used in certain cases of Waldenstrom macroglobulinemia because most patients are older, the treatment does not work equally well for each patient, and there are serious risks with this treatment. Side effects depend on the type of transplant, your general health, and other factors. Learn more about the basics of stem cell and bone marrow transplantation.

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Physical, emotional, and social effects of cancer

Cancer and its treatment cause physical symptoms and side effects, as well as emotional, social, and financial effects. Managing all of these effects is called palliative care or supportive care. It is an important part of your care that is included along with treatments intended to slow, stop, or eliminate the cancer.

Palliative care focuses on improving how you feel during treatment by managing symptoms and supporting patients and their families with other, non-medical needs. Any person, regardless of age or type and stage of cancer, may receive this type of care. And it often works best when it is started right after a cancer diagnosis. People who receive palliative care along with treatment for the cancer often have less severe symptoms, better quality of life, and report that they are more satisfied with treatment.

Palliative treatments vary widely and often include medication, nutritional changes, relaxation techniques, emotional and spiritual support, and other therapies. For instance, plasma exchange (described above) is a type of supportive care. You may also receive palliative treatments similar to those meant to get rid of the cancer, such as chemotherapy.

Before treatment begins, talk with your doctor about the goals of each treatment in the recommended treatment plan. You should also talk about the possible side effects of the specific treatment plan and palliative care options. Many patients also benefit from talking with a social worker and participating in support groups. Ask your doctor about these resources, too.

During treatment, your health care team may ask you to answer questions about your symptoms and side effects and to describe each problem. Be sure to tell the health care team if you are experiencing a problem. This helps the health care team treat any symptoms and side effects as quickly as possible. It can also help prevent more serious problems in the future.

Learn more about the importance of tracking side effects in another part of this guide. Learn more about palliative care in a separate section of this website.

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Refractory Waldenstrom macroglobulinemia

If treatment does not stop or eliminate the disease, this is called refractory Waldenstrom macroglobulinemia. If this happens, it is a good idea to talk with doctors who have experience in treating it. Doctors can have different opinions about the best standard treatment plan. Usually, your doctor may try one of the other available treatments discussed above. Clinical trials might also be an option. Learn more about getting a second opinion before starting treatment, so you are comfortable with your chosen treatment plan.

Your treatment plan may include a combination of different medications to treat the cancer. Palliative care, also called supportive care, will also be important to help relieve symptoms and side effects.

For many people, this diagnosis is very stressful and difficult. You and your family are encouraged to talk about how you are feeling with doctors, nurses, social workers, or other members of your health care team. It may also be helpful to talk with other patients, such as through a support group or other peer support program.

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Remission and the chance of recurrence

A remission is when cancer cannot be detected in the body and there are no symptoms. This may also be called having “no evidence of disease” or NED.

A remission is usually temporary, even though it can last several years for some people. This uncertainty causes many people to worry about when the cancer will come back. It is important to talk with your doctor about the possibility of the cancer returning. Understanding your risk of recurrence and the treatment options may help you feel more prepared if the cancer does return. Learn more about coping with the fear of recurrence.

If Waldenstrom macroglobulinemia comes back after the original treatment, it is called recurrent or relapsed disease. If a recurrence happens, a new cycle of testing will begin again to learn as much as possible about it. Very rarely, the recurrence may come as a different type of lymphoma, usually diffuse large B-cell lymphoma (DLBCL).

After this testing is done, you and your doctor will talk about the treatment options. Often the treatment plan will include the treatments described above, such as chemotherapy, targeted therapy, and rarely, bone marrow/stem cell transplantation. But they may be used in a different combination or given at a different pace. Your doctor may suggest clinical trials that are studying new ways to treat recurrent Waldenstrom macroglobulinemia. There are currently several new drugs and combinations of different therapies being researched in clinical trials. Whichever treatment plan you choose, palliative care or supportive care will be important for relieving symptoms and side effects.

People with recurrent cancer sometimes experience emotions such as disbelief or fear. You are encouraged to talk with your health care team about these feelings and ask about support services to help you cope. Learn more about dealing with cancer recurrence.

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If treatment does not work

Recovery from cancer is not always possible. If the cancer cannot be cured or controlled, the disease may be called advanced or terminal.

This diagnosis is stressful, and for some people, advanced cancer is difficult to discuss. However, it is important to have open and honest conversations with your health care team to express your feelings, preferences, and concerns. The health care team has special skills, experience, and knowledge to support patients and their families and is there to help. Making sure a person is physically comfortable, free from pain, and emotionally supported is extremely important.

People who have advanced cancer and who are expected to live less than 6 months may want to consider hospice care. Hospice care is designed to provide the best possible quality of life for people who are near the end of life. You and your family are encouraged to talk with the health care team about hospice care options, which include hospice care at home, a special hospice center, or other health care locations. Nursing care and special equipment can make staying at home a workable option for many families. Learn more about advanced cancer care planning.

After the death of a loved one, many people need support to help them cope with the loss. Learn more about grief and loss.

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The next section in this guide is About Clinical Trials. It offers more information about research studies that are focused on finding better ways to care for people with cancer. Use the menu to choose a different section to read in this guide.