Waldenstrom Macroglobulinemia

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Treating Waldenstrom Macroglobulinemia TOPICS

Biological therapy or immunotherapy for Waldenstrom macroglobulinemia

Biological therapies help the body’s immune system fight the cancer or use man-made versions of substances normally made by the immune system. These substances can kill Waldenstrom macroglobulinemia (WM) cells or slow their growth.

Monoclonal antibodies

Antibodies are proteins made by the body’s immune system to help fight infections. Man-made versions, called monoclonal antibodies, can be designed to attack a specific target, such as a substance on the surface of lymphocytes (the cells in which lymphomas like WM start).

Some monoclonal antibodies are now being used to treat lymphomas, including WM.

Rituximab (Rituxan®) is the most widely used monoclonal antibody for lymphoma, including WM. It attaches to a protein that is found on the surface of lymphoma cells called CD20. This attachment tells the lymphoma cell to die. Patients get rituximab by infusion into a vein (IV) at the doctor’s office or clinic. Rituximab can be given alone or with chemotherapy as a part of treatment.

This drug has to be given carefully in patients with WM because sometimes it can actually raise the level of IgM in the blood at first, which can lead to problems with hyperviscosity (thickened blood). Side effects during the infusion are common, and can include chills, fever, nausea, rashes, fatigue, and headaches. Unlike regular chemotherapy, rituximab does not cause low blood counts or hair loss.

Ofatumumab (Arzerra®) is another antibody that targets the CD20 antigen. It can be used in people who have trouble taking rituximab. Side effects are similar to those seen with rituximab, including an increased risk of IgM levels going up when the drug is first given.

Alemtuzumab (Campath®) is directed at a different protein on lymphoma cells called CD52. This drug is more commonly used to treat patients with chronic lymphocytic leukemia, but it has also helped some patients with WM. It is given by infusion into a vein (IV) or under the skin, usually 3 times a week. A serious side effect of alemtuzumab is a large drop in blood cell counts that can last weeks or even months. People on this drug can develop life-threatening infections that are hard to treat while their white blood cells are low.

Immunomodulating agents

These drugs are thought to work against certain cancers by affecting parts of a person’s immune system, although exactly how they work is not clear. They are most often used to treat multiple myeloma, but they might also be helpful in treating WM.

Thalidomide, the first of these drugs to be developed, caused severe birth defects when taken during pregnancy. There is concern that other related drugs could also cause birth defects. Because of this, these drugs can only be obtained through a special program run by the drug company that makes them.

Thalidomide (Thalomid®) is used to treat multiple myeloma, and can also help some WM patients. A problem with this drug is that many patients have trouble tolerating some of its side effects. These include drowsiness, fatigue (tiredness), severe constipation, and neuropathy (painful nerve damage). The neuropathy can be severe, and might not go away after the drug is stopped. There is also an increased risk of serious blood clots that start in the leg and can travel to the lungs. The best results with thalidomide in WM have been seen when it is given along with other drugs, such as rituximab or dexamethasone.

Lenalidomide (Revlimid®) is a drug similar to thalidomide. It is often used to treat multiple myeloma. In studies of patients with WM, patients have shown improvement in their IgM and beta-2 microglobulin levels, but often developed worsening anemia (low red blood cell counts). The role of this drug in treating WM is still being explored. The other most common side effects are low platelet counts and low white blood cell counts. It can also cause painful nerve damage. The risk of blood clots is not as high as that seen with thalidomide, but it is still elevated.

Pomalidomide (Pomalyst®) is also related to thalidomide and is used to treat multiple myeloma. Studies are now looking at whether it can help treat WM as well. Some common side effects include anemia (low red blood cell counts) and low white blood cell counts. It is also linked to an increased risk of blood clots. The risk of nerve damage is not as high as with the other immunomodulating drugs.


Cytokines are hormone-like proteins normally made by white blood cells to help the immune system fight infections.

Interferon is a cytokine that can be made in the lab to give to patients as a drug. Some studies have suggested that interferon can make some lymphoma tumors shrink. Side effects of this treatment include moderate to severe fatigue, fever, chills, headaches, muscle and joint aches, and mood changes.

It is still not certain whether interferon is a good option for patients with non-Hodgkin lymphoma or WM. It is most often used only in patients who continue to get sicker after treatment with other drugs.

To learn more about biologic treatments and immunotherapies for cancer, you can read our document Immunotherapy. If you are interested in learning about a specific cancer treatment drug, see the “Guide to Cancer Drugs” on our website, or call us for more specific information.

Last Medical Review: 06/19/2013
Last Revised: 06/19/2013