Biological therapies use naturally occurring substances produced by the immune system. These substances may kill lymphoma cells, slow their growth, or may activate the patient's immune system to more effectively fight the lymphoma.

Immunotherapy with monoclonal antibodies

Antibodies are normally produced by the immune system to help fight infections. Monoclonal antibodies designed to attack lymphoma cells are made in the laboratory.

Rituximab (Rituxan) is the most widely used monoclonal antibody for lymphoma. Rituximab specifically recognizes and attaches to a protein that is found on the surface of lymphoma cells called CD20. This attachment tells the lymphoma cell to die. Patients receive rituximab by infusion into a vein (IV) at the oncologist's office or clinic. Side effects during the infusion are very common, and include chills, fever, nausea, rashes, fatigue, and headaches. Unlike regular chemotherapy, rituximab does not cause low blood counts or hair loss. This treatment is one of the standard treatments for lymphoma and Waldenstrom macroglobulinemia (WM). Rituximab can be given alone or with regular chemotherapy as a part of treatment.

Alemtuzumab (Campath): Another monoclonal antibody, called 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. A serious side effect of alemtuzumab is a large drop in the blood counts that can last weeks. People on this drug can develop life-threatening infections that are hard to treat while their white blood cells are low.

Immunomodulating agents

The drug thalidomide 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 the side effects that occur when higher doses of thalidomide are used (such as when it is used alone). Side effects of thalidomide include drowsiness, fatigue, severe constipation, and neuropathy (painful nerve damage). The neuropathy can be severe, and may 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. Because thalidomide causes severe birth defects if it is taken during pregnancy, it can only be obtained through a special program run by the drug company that makes it. The best results with thalidomide in WM occurred when it was given along with other drugs, such as rituximab or dexamethasone.

Lenalidomide (Revlimid) is a newer drug similar to thalidomide. It is often used to treat multiple myeloma. In studies of patients with WM, the patients showed improvement in their IgM and beta-2-microglobulin levels, but developed worsening anemia. The role of this drug in treating WM is still being explored. The most common side effects of lenalidomide are thrombocytopenia (low platelets) and low white blood cell counts. The risk of blood clots is not as high as that seen with thalidomide, but it is still elevated. Like thalidomide, access to lenalidomide is also tightly controlled out of concern about possible serious birth defects.

Interferon is a hormone-like protein naturally produced by white blood cells to help the immune system fight infections. Some studies have suggested that interferon can cause some lymphoma tumors to 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 the best treatment for some patients who have non-Hodgkin lymphoma or WM. It is usually used only in patients who continue to get sicker after treatment with standard chemotherapy drugs.

Last Medical Review: 08/04/2009
Last Revised: 08/04/2009