Waldenstrom’s Macroglobulinemia: Treatment Options

Approved by the Cancer.Net Editorial Board, 04/2016

ON THIS PAGE: You will learn about the different ways doctors use to treat people with this type of cancer. To see other pages, use the menu.

This section tells you the treatments that are the standard of care for this type of cancer. “Standard of care” means the best treatments known. When making treatment plan decisions, patients are also encouraged to consider clinical trials as an option. A clinical trial is a research study that tests a new approach to treatment. Doctors want to learn if it 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. Your doctor can help you consider all your treatment options. To learn more about clinical trials, see the Clinical Trials and Latest Research sections.

Treatment overview

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 also include a variety of other health care professionals, including physician assistants, oncology nurses, social workers, pharmacists, counselors, dietitians, and others.

Descriptions of the most common treatment options for Waldenstrom’s macroglobulinemia are listed below. 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. Your care plan may also include treatment for symptoms and side effects, an important part of cancer care. 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. Treatment for Waldenstrom’s is to treat the disease and/or to relieve the symptoms for as many years as possible. Be sure to talk with your health care team to understand the goals of each treatment. Learn more about making treatment decisions.

Watchful waiting

Some patients with Waldenstrom’s 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 IgM level increases. This is called watchful waiting, watch-and-wait, or active surveillance. There is very good evidence that, in some patients 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.

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’s macroglobulinemia from the elevated IgM level. During this procedure, blood is taken from a vein, and plasma—the liquid part of the blood—is removed from the body after it is separated from the red and white blood cells. The blood cells are then mixed with a plasma substitute, usually an albumin solution, and returned to the patient. This procedure is usually done using a blood cell separator.


Chemotherapy is the use of drugs to destroy cancer cells, usually by stopping the cancer cells’ ability to grow and divide. Chemotherapy is given by a medical oncologist or hematologist, doctors who specialize in treating this type of cancer with medication.

Systemic chemotherapy gets into the bloodstream to reach cancer cells throughout the body. Common ways to give chemotherapy include an intravenous (IV) tube placed into a vein using a needle or in a pill or capsule that is swallowed.

A chemotherapy regimen (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 combinations of different drugs at the same time. Common drugs for Waldenstrom’s macroglobulinemia include chlorambucil (Leukeran), cladribine (Leustatin), cyclophosphamide (Neosar), and fludarabine (Fludara). Bendamustine (Treanda) is a chemotherapy treatment that can be used to treat Waldenstrom’s macroglobulinemia when it is first diagnosed or when it returns.

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, hair loss, loss of appetite, and diarrhea. These side effects usually go away once treatment is finished.

Learn more about the basics of chemotherapy and preparing for treatment. 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. Learn more about your prescriptions by using searchable drug databases.

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 while limiting damage to healthy cells.

Recent studies show that 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, many research studies are taking place now to find out more about specific molecular targets and new treatments directed at them. Learn more about the basics of targeted treatments.

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 cell-surface molecule called CD20. When the antibody attaches to this antigen, 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’s macroglobulinemia. Although it is quite effective by itself, there is increasing evidence that, for people with most types of B-cell non-Hodgkin lymphoma, rituximab works better when combined with chemotherapy.

Another targeted therapy, called ibrutinib (Imbruvica), works to target BTK proteins in cancerous B-cells. Ibrutinib was approved in January 2015 by the Food and Drug Administration (FDA) as a treatment for Waldenstrom’s macroglobulinemia, after earlier approvals for 2 other types of blood-related cancers. And, Bortezomib (Velcade) is a 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.

Stem cell transplantation/bone marrow transplantation

A stem cell transplant is a medical procedure in which bone marrow that contains cancer is replaced by highly specialized cells, called hematopoietic stem cells, that develop into healthy bone marrow. Hematopoietic stem cells are found both in the bloodstream and in the bone marrow. Today, this procedure is more commonly called a stem cell transplant, rather than bone marrow transplant, because it is the stem cells in the blood that are typically being transplanted, not the actual bone marrow tissue.

Transplantation is not used often for people with Waldenstrom’s macroglobulinemia because most patients are older, the treatment does not work equally well for each patient, and there are serious risks with this treatment. Learn more about the basics of bone marrow and stem cell transplantation.

Getting care for symptoms and side effects

Cancer and its treatment often cause side effects. In addition to treatment to slow, stop, or eliminate the cancer, an important part of cancer care is relieving a person’s symptoms and side effects. This approach is called palliative or supportive care, and it includes supporting the patient with his or her physical, emotional, and social needs.

Palliative care is any treatment that focuses on reducing symptoms, improving quality of life, and supporting patients and their families. Any person, regardless of age or type and stage of cancer, may receive palliative care. It works best when palliative care is started as early as needed in the cancer treatment process. People often receive treatment for the cancer and treatment to ease side effects at the same time. In fact, patients who receive both often have less severe symptoms, better quality of life, and report they are more satisfied with treatment.

Palliative treatments vary widely and often include medication, nutritional changes, relaxation techniques, emotional support and other therapies. You may also receive palliative treatments similar to those meant to eliminate the cancer, such as chemotherapy, surgery, or radiation therapy. Talk with your doctor about the goals of each treatment in the treatment plan.

Before treatment begins, talk with your health care team about the possible side effects of your specific treatment plan and palliative care options. And during and after treatment, be sure to tell your doctor or another health care team member if you are experiencing a problem so it can be addressed as quickly as possible. Learn more about palliative care.   

Refractory Waldenstrom’s macroglobulinemia

If treatment does not stop or eliminate the disease, this is called refractory Waldenstrom’s 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. Also, clinical trials might be an option. Learn more about getting a second opinion before starting treatment, so you are comfortable with your treatment plan chosen.

Your treatment plan may include a combination of different chemotherapy drugs. Palliative care will also be important to help relieve symptoms and side effects.

For most patients, this diagnosis is very stressful and, at times, difficult to bear. Patients and their families are encouraged to talk about the way they are feeling with doctors, nurses, social workers, or other members of the health care team. It may also be helpful to talk with other patients, including through a support group.

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 may be temporary or permanent. This uncertainty causes many people to worry that the cancer will come back. While many remissions are permanent, 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’s macroglobulinemia returns after the original treatment, it is called recurrent disease. When this occurs, a set of tests will begin again to learn as much as possible about the recurrence. After testing is done, you and your doctor will talk about your treatment options. Often the treatment plan will include the treatments described above, such as chemotherapy, targeted therapy, and bone marrow/stem cell transplantation, but they may be used in a different combination or given at a different pace. Your doctor may also suggest clinical trials that are studying new ways to treat this type of recurrent cancer. Whichever treatment plan you choose, palliative care will be important for relieving symptoms and side effects.

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

If treatment fails

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

Patients who have advanced cancer and who are expected to live less than 6 months may want to consider a type of palliative care called 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 think about where you would be most comfortable: at home, in the hospital, or in a hospice environment. Nursing care and special equipment can make staying at home a workable alternative 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.

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. Or, use the menu to choose another section to continue reading this guide.