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. These treatments may kill lymphoma 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 start).

Several monoclonal antibodies are now used to treat lymphoma.

Antibodies that target CD20

A number of monoclonal antibody drugs used to treat NHL target the CD20 antigen, a protein found on the surface of B lymphocytes. These include:

  • Rituximab (Rituxan)
  • Obinutuzumab (Gazyva)
  • Ofatumumab (Arzerra)
  • Ibritumomab tiuxetan (Zevalin)

Rituximab is often used along with chemotherapy, either as part of the initial treatment or as part of a second-line regimen, but it may also be used by itself.

Obinutuzumab is often used along with the chemo drug chlorambucil as a part of the initial treatment for small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). It might also be used along with the chemo drug bendamustine in treating follicular lymphoma after other treatments have been tried.

Ofatumumab is used mainly in patients with SLL/CLL that is no longer responding to other treatments such as chemotherapy or other monoclonal antibodies such as alemtuzumab (discussed below).

Ibritumomab tiuxetan is made up of a monoclonal antibody aimed at CD20 that has a radioactive molecule attached to it. The antibody brings radiation directly to the lymphoma cells.

These drugs are infused into a vein (IV), which can take up to several hours depending on the drug. They all can cause side effects during the infusion (while the drug is being given) or several hours afterward. These can be mild, such as itching, chills, fever, nausea, rashes, fatigue, and headaches.

More serious side effects can also occur during the infusion, including chest pain, heart racing, swelling of the face and tongue, cough, trouble breathing, feeling dizzy or light headed, and feeling faint. Because these kinds of reactions are common with obinutuzumab and ofatumumab, drugs to help prevent serious problems will be given before each infusion.

Ibritumomab tiuxetan causes low blood cell counts more often than the other antibodies that target CD20.

All of these drugs can cause hepatitis B infections that were dormant (inactive) to become active again, which can lead to severe liver problems or even death. For that reason, your doctor may check your blood for signs of an old hepatitis infection before starting this drug. If your blood shows signs of an old hepatitis B infection, the doctor will check your blood during treatment to see if the virus becomes active again. If it does, the drug will need to be stopped.

These drugs may also increase a person's risk of certain serious infections for many months after the drug is stopped.

Other side effects can occur depending on which drug is given. Ask your doctor what you can expect.

In rare cases of patients with very high white blood cell counts, some of these drugs may cause a condition called tumor lysis syndrome (this was discussed in detail in the chemotherapy section). This happens when the drug kills the cancer cells so quickly that the body has trouble getting rid of the breakdown products of the dead cells. It generally only occurs during the first course of treatment.

Antibodies targeting CD52

Alemtuzumab (Campath) is an antibody directed at the CD52 antigen. It is useful in some cases of small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) and also some types of peripheral T-cell lymphomas. It 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. Some lymphoma cells have the CD30 molecule on their surface. The antibody acts like a homing signal, bringing the chemo drug to the lymphoma cells, where it enters the cells and causes them to die when they try to divide into new cells.

Brentuximab can be used to treat anaplastic large cell lymphoma (ALCL) that has come back after other treatments. It is infused into a vein (IV) every 3 weeks. Common side effects include nerve damage (neuropathy), low blood counts, fatigue, fever, nausea and vomiting, infections, diarrhea, and cough.


Interferon is a hormone-like protein made by white blood cells to help the immune system fight infections. 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 agents

These drugs are thought to work against certain cancers by affecting parts of a person’s 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.

Thalidomide (Thalomid): This drug is mainly used to treat another cancer of the lymphocytes known as multiple myeloma, but it can also be used to treat some types of lymphoma.

Side effects of thalidomide include drowsiness, fatigue, severe constipation, low white blood cell counts (with an increased risk of infection), 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 taken during pregnancy, the company that makes it puts restrictions on access to it to prevent women who are or might become pregnant from being exposed to it.

Lenalidomide (Revlimid): This is a newer drug that is similar to thalidomide. It may be used to treat some types of lymphoma.

The most common side effects of lenalidomide are low platelet counts (with an increased risk of bleeding) and low white blood cell counts (with an increased risk of infection). It can also cause painful nerve damage. The risk of blood clots isn’t as high as with thalidomide, but it is still increased. Like thalidomide, access to lenalidomide is tightly controlled out of concern about possible serious birth defects.

More information on immunotherapy can be found in our document 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.

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: August 26, 2014 Last Revised: February 29, 2016

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