Immunotherapy for Non-Hodgkin Lymphoma

Immunotherapy is treatment that either boosts the patient’s own immune system or uses man-made versions of the normal parts of the immune system to kill lymphoma cells or slow their growth.

Monoclonal antibodies

Antibodies are proteins made by your 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 start). 

Several monoclonal antibodies are now used to treat non-Hodgkin lymphoma (NHL). 

Antibodies that target CD20

A number of monoclonal antibodies target the CD20 antigen, a protein on the surface of B lymphocytes. These include:

  • Rituximab (Rituxan): This drug is often used along with chemotherapy for some types of NHL, but it may also be used by itself.
  • Obinutuzumab (Gazyva): This drug is often used along with chemo as a part of the treatment for small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). It might also be used along with chemo in treating follicular lymphoma after other treatments have been tried.
  • Ofatumumab (Arzerra): This drug is used mainly in patients with SLL/CLL that is no longer responding to other treatments.
  • Ibritumomab tiuxetan (Zevalin): This drug is made up of a monoclonal antibody that is attached to a radioactive molecule. The antibody brings radiation directly to the lymphoma cells.

These drugs are given into a vein (IV), often over several hours. They all can cause reactions during the infusion (while the drug is being given) or several hours afterward. These are usually mild, such as itching, chills, fever, nausea, rashes, fatigue, and headaches. More serious reactions can include chest pain, heart racing, swelling of the face and tongue, cough, trouble breathing, feeling dizzy or lightheaded, and feeling faint. Because of these kinds of reactions, drugs to help prevent them are given before each infusion. 

There is also a form of rituximab that is given as a shot under the skin. It can take 5-7 minutes to inject the drug, but this is much shorter than the time it normally takes to give the drug by vein. It is approved for use in patients with follicular lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia. Possible side effects include local skin reactions, like redness, where the drug is injected, infections, low white blood cell counts, nausea, fatigue, and constipation.

All of these drugs can cause hepatitis B infections that were inactive to become active again, which can lead to severe or life-threatening liver problems. Your doctor may check your blood for signs of an old hepatitis B infection before you start treatment. These drugs can also increase your risk of certain serious infections for many months after the drug is stopped. Other side effects can depend on which drug is given. Ask your doctor what you can expect.

Antibodies targeting CD52

Alemtuzumab (Campath) is an antibody directed at the CD52 antigen. It is useful in some cases of SLL/CLL and some types of peripheral T-cell lymphomas. This drug is infused into a vein (IV), usually 3 times a week for up to 12 weeks. The most common side effects are fever, chills, nausea, and rashes. It can also cause very low white blood cell counts, which increases the risk for serious infections. Antibiotic and antiviral medicines are given to help protect against them, but severe and even life-threatening infections can still occur. 

Antibodies that target CD30

Brentuximab vedotin (Adcetris) is an anti-CD30 antibody attached to a chemotherapy drug. The antibody acts like a homing signal, bringing the chemo drug to lymphoma cells, where it enters the cells and kills them. 

Brentuximab can be used to treat some types of lymphoma, especially if it has come back after other treatments. This drug is infused into a vein (IV), typically every 3 weeks. Common side effects can include nerve damage (neuropathy), low blood counts, fatigue, fever, nausea and vomiting, infections, diarrhea, and cough. 

Interferon

Interferon is a chemical made by white blood cells that can help boost the immune system. Some studies have suggested that giving man-made interferon can make some types of lymphomas shrink or stop growing.

Common side effects of this treatment include fatigue, fever, chills, headaches, muscle and joint aches, and mood changes. Because of the side effects, interferon is not used very often. It might be given to some patients in addition to chemotherapy.

Immunomodulating drugs 

Drugs such as thalidomide (Thalomid) and lenalidomide (Revlimid) are thought to work against certain cancers by affecting parts of the immune system, although exactly how they work isn’t clear. They are sometimes used to help treat certain types of lymphoma, usually after other treatments have been tried.

These drugs are taken daily as pills. Side effects of can include low white blood cell counts (with an increased risk of infection) and neuropathy (painful nerve damage), which can sometimes be severe and may not go away after treatment. There is also an increased risk of serious blood clots (that start in the leg and can travel to the lungs), especially with thalidomide. Thalidomide can also cause drowsiness, fatigue, and severe constipation.

Because these drugs can cause severe birth defects if taken during pregnancy, the company that makes them puts restrictions on access to them to prevent women who are or might become pregnant from being exposed to them. 

For more on immunotherapy, see Cancer Immunotherapy.

The American Cancer Society medical and editorial content team
Our team is made up of doctors and master’s-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Freedman AS, Jacobson CA, Mauch P, Aster JC. Chapter 103: Non-Hodgkin’s lymphoma. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2015.

National Cancer Institute. Physician Data Query (PDQ). Adult Non-Hodgkin Lymphoma Treatment. 2016. Accessed at www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq on May 15, 2016.

National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Non-Hodgkin’s Lymphomas. Version 3.2016. Accessed at www.nccn.org/professionals/physician_gls/pdf/nhl.pdf on May 11, 2016.

Roschewski MJ, Wilson WH. Chapter 106: Non-Hodgkin Lymphoma. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff’s Clinical Oncology. 5th ed. Philadelphia, Pa: Elsevier; 2014.

Last Medical Review: May 31, 2016 Last Revised: May 31, 2016

American Cancer Society medical information is copyrighted material. For reprint requests, please see our Content Usage Policy.