Immunotherapy with monoclonal antibodies: Antibodies are normally produced by the immune system to help fight infections. Monoclonal antibodies that have been 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) infusions at the oncologist's office or clinic. Side effects are most common during the infusion, 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 WM. Rituximab can be given alone or together 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 (CLL), but it has also helped some patients with Waldenstrom macroglobulinemia. 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 has been given to WM patients in a few small studies with some improvement. Many patients could not tolerate the higher doses of thalidomide that are required when it is used alone. The best results with thalidomide in WM have been when it was given at a low dose along with the antibiotic clarithromycin (Biaxin) and the corticosteroid dexamethasone. Side effects of thalidomide include drowsiness, fatigue, severe constipation, and neuropathy (nerve damage causing pain). 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 taken during pregnancy, this drug can only be obtained through a special program run by the drug company that makes it.

Lenalidomide (Revlimid) is a newer drug that is similar to thalidomide. It works well in multiple myeloma but has not yet been studied in WM. 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 what is 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 tumors of some lymphomas 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 Waldenstrom macroglobulinemia. It is usually used only in patients who continue to get sicker after treatment with standard chemotherapy drugs.