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 (chemo) 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 can also be used along with chemo in treating follicular lymphoma.
  • 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. Most reactions are 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 inactive hepatitis B infections 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. Rare but serious side effects can include strokes, as well as tears in the blood vessels in the head and neck.

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 T-cell lymphoma, either as the first treatment (typically along with chemo) or if the lymphoma 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. 

Antibodies that target CD79b

Polatuzumab vedotin-piiq (Polivy) is an anti-CD79b antibody (polatuzumab) attached to a chemotherapy drug (MMAE). The antibody finds the lymphoma cell and attaches to the surface protein CD79b.  Once connected, polatuzumab is drawn into the lymphoma cell where the chemo is released and destroys it.

Polatuzumab can be used with bendamustine and rituximab to treat DLBCL, if the lymphoma has come back after receiving two other treatments. This drug is infused into a vein (IV), typically every 3 weeks. Common side effects can include numbness or tingling of hands/feet (peripheral neuropathy), low blood counts, fatigue, fever, decreased appetite, diarrhea, and pneumonia.

Immune checkpoint inhibitors

Immune system cells normally have substances that act as checkpoints to keep them from attacking other healthy cells in the body. Cancer cells sometimes take advantage of these checkpoints to avoid being attacked by the immune system.

Drugs such as pembrolizumab (Keytruda) work by blocking these checkpoints, which can boost the immune response against cancer cells. Pembrolizumab can be used to treat primary mediastinal large B-cell lymphoma (PMBCL) that has not responded to or has come back after other therapies.  

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. Lenalidomide can be given with or without rituximab.

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.

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

Chimeric antigen receptor (CAR) T-cell therapy

In this treatment, immune cells called T cells are removed from the patient’s blood and altered in the lab to have specific receptors (called chimeric antigen receptors, or CARs) on their surface. These receptors can attach to proteins on the surface of lymphoma cells. The T cells are then multiplied in the lab and given back into the patient’s blood, where they can seek out the lymphoma cells and launch a precise immune attack against them.

Axicabtagene ciloleucel (Yescarta) is a type of CAR T-cell therapy approved by the FDA to treat people with diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma and diffuse large B-cell lymphoma arising from follicular lymphoma after at least two other kinds of treatment have been tried. Because this treatment can have serious side effects, it is only given in medical centers that have special training with this treatment. Potentially life-threatening side effects can include high fever, chills, flu-like symptoms, and serious neurological changes. Other severe side effects include infection, low blood cell counts, and a weakened immune system.

Tisagenlecleucel (Kymriah) is another type of CAR T-cell therapy approved to treat people with diffuse large B cell lymphoma, high grade B cell lymphoma, and diffuse large B cell lymphoma arising from follicular lymphoma after trying at least two other kinds of treatment. Potentially life-threatening side effects can include fever, headache, low blood pressure, a fast heart rate, and trouble breathing. Other severe side effects include infection, diarrhea, swelling, and nausea. This drug must also be given in centers with specialized training.  

To learn more, see CAR T-Cell Therapies.

More information about immunotherapy

To learn more about how drugs that work on the immune system are used to treat cancer, see Cancer Immunotherapy.

To learn about some of the side effects listed here and how to manage them, see Managing Cancer-related Side Effects.

The American Cancer Society medical and editorial content team

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

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Last Medical Review: August 1, 2018 Last Revised: June 20, 2019

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