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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 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 WM starts).

Rituximab (Rituxan) is the most widely used monoclonal antibody for WM. It attaches to a protein called CD20 on the surface of lymphoma cells . 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 or targeted therapy (or other drugs) as a part of treatment.

This drug has to be given carefully to WM patients 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 for 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 also helps 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. Rare but serious side effects can include strokes, as well as tears in the blood vessels in the head and neck.

Immunomodulating drugs

Immunomodulating drugs (IMiDs) are thought to work against certain cancers by boosting parts of your immune system, although exactly how they work is not clear. These drugs are most often used to treat multiple myeloma, but they might also be helpful in treating WM.

Thalidomide (Thalomid) is the IMiD with the most evidence showing it can help some patients with WM. But many patients have trouble tolerating some of the side effects of this drug. These include drowsiness, fatigue (tiredness), severe constipation, and neuropathy (painful nerve damage). The neuropathy 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.

Pomalidomide (Pomalyst) is a newer IMiD that generally cause less severe side effects than thalidomide. It is used mainly to treat multiple myeloma, but studies are now looking at whether it can help treat WM as well.

Because of concerns these drugs can cause severe birth defects if taken during pregnancy, they can only be obtained through special programs run by the drug company that makes them.

Cytokines

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

Interferon is a cytokine that can be made in the lab and given to patients. 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 WM. It is most often used only in patients who continue to get sicker after treatment with other drugs.