Non-Hodgkin Lymphoma

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Immunotherapy for Non-Hodgkin Lymphoma

Immunotherapy is the use of medicines to help your own immune system better recognize and destroy cancer cells or slow their growth. These medicines are now an important part of treatment for many types of non-Hodgkin lymphoma (NHL).

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Monoclonal antibodies

Antibodies are proteins made by your immune system to help fight infections. Human-made versions of these proteins are called monoclonal antibodies. They can be designed to attack a specific target, such as a substance on the surface of lymphocytes. Lymphocytes are the cells in which lymphoma starts.

Many monoclonal antibodies are now used to treat different types of NHL.

Antibodies that target CD20

A number of monoclonal antibodies target the CD20 antigen, a protein on the surface of B lymphocytes. These drugs are given into a vein (IV), often over several hours. They include:

This drug is often used along with chemotherapy (chemo) for some types of NHL. It may also be used by itself.

Possible side effects

  • Infusion reaction: Rituximab can cause an infusion reaction 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. Before each infusion, you will get medicines to help prevent this type of reaction.
  • Hepatitis B reactivation: This drug can cause inactive hepatitis B infections to become active again. When this happens, it can lead to severe or life-threatening liver problems. Your cancer care team may check your blood for signs of an old hepatitis B infection before you start treatment.
  • Serious infection: It can also increase your risk of certain serious infections for many months after treatment.

Other side effects can also happen. Ask your cancer care team what you can expect.

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.

Possible side effects

  • Infusion reaction: Obinutuzumab can cause an infusion reaction 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. Before each infusion, you will get medicines to help prevent this type of reaction.
  • Hepatitis B reactivation: This drug can cause inactive hepatitis B infections to become active again. When this happens, it can lead to severe or life-threatening liver problems. Your cancer care team may check your blood for signs of an old hepatitis B infection before you start treatment.
  • Serious infection: It can also increase your risk of certain serious infections for many months after treatment.

Other side effects can also happen. Ask your cancer care team what you can expect.

This form of rituximab is given as a shot under the skin. It can take 5 to 7 minutes to inject the drug. However, this is much shorter than the time it normally takes to give the drug by IV.

It is approved for use in people 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
  • Constipation

Hepatitis B re-activation: This drug can cause inactive hepatitis B infections to become active again. When this happens, it can lead to severe or life-threatening liver problems. Your cancer care team may check your blood for signs of an old hepatitis B infection before you start treatment.

Serious infection: This drug can also increase your risk of certain serious infections for many months after treatment.

Other side effects can also happen. Ask your cancer care team what you can expect.

Possible side effects of these drugs

See the information on each individual drug (above) for a list of its possible side effects.

T-cell engagers (TCEs) that target CD20

T-cell engagers (TCEs) are a newer type of monoclonal antibody known as a bispecific antibody. These antibodies are designed so they can attach to 2 different targets.

Once it is in your body, one part of the antibody attaches to the CD3 protein on T cells. T cells are a type of immune cell. Another part of the antibody attaches to a target on lymphoma cells, such as the CD20 protein. This brings the two cells together, which helps your immune system see and attack the lymphoma cells.

This drug can be used to treat follicular lymphoma that has returned or is no longer responding after treatment with at least 2 other types of drugs. It is either put into a vein (IV) or injected under the skin. It is typically given once a week for the first 3 weeks, then once every 3 weeks.

This drug can be used to treat diffuse large B-cell lymphoma (DLBCL) and other high-grade B-cell lymphomas, or follicular lymphoma, typically after other treatments have been tried. It is injected under the skin (subcutaneous). It is usually given once a week for the first 3 months, then once or twice a month.

Epcoritamab in combination with rituximab and lenalidomide (R2)

This combination is now approved to treat relapsed or refractory follicular lymphoma. It is given in the same way as epcoritamab alone.

This drug can be used to treat diffuse large B-cell lymphoma (DLBCL) or large B-cell lymphoma (LBCL) arising from follicular lymphoma, typically after 2 or more other treatments have been tried.

It is put into a vein (IV) on a step-up dosing schedule. Lower doses are given first to reduce the risk of cytokine release syndrome, then once every 3 weeks for up to 12 cycles.

Possible side effects of TCEs

These drugs can cause some of the same side effects as other antibodies that target CD20.

For example, mosunetuzumab can cause an infusion reaction. 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. Before each infusion, you will get medicines to help prevent this type of reaction.

Other side effects can include feeling tired, muscle or bone pain, rash, fever, nausea, diarrhea, and headaches.

These drugs can also cause some other, more serious side effects, including:

Nervous system problems: These drugs might affect the nervous system. This can lead to symptoms such as headaches, numbness or tingling in your hands or feet, feeling dizzy or confused, having trouble speaking or understanding things, memory loss, abnormal sleep patterns, tremors, or seizures.

Serious infections: Some people might get a serious infection while taking one of these drugs. Tell your cancer care team right away if you have a fever, cough, chest pain, shortness of breath, sore throat, rash, or pain when urinating.

Low blood cell counts: These drugs might lower your blood cell counts, which can increase your risk of infections or bleeding. Your cancer care team will check your blood cell counts regularly during your treatment.

Tumor flare: These drugs might cause your tumor to grow or cause more symptoms for a time. This is known as tumor flare. Tell your cancer care team if you notice tender or swollen lymph nodes, chest pain, cough, trouble breathing, or pain or swelling around a known tumor.

Cytokine release syndrome (CRS): This side effect can happen when T cells in your body release chemicals (cytokines) into your blood and the chemicals ramp up your immune system. It usually happens within the first day after treatment. It can be serious or even life-threatening.

Symptoms of CRS can include high fever and chills, muscle weakness, trouble breathing, low blood pressure, a very fast heartbeat, headache, nausea or vomiting, and feeling dizzy, lightheaded, or confused.

Your cancer care team will watch you closely for possible signs of CRS, especially during and after the first few treatments. You may get medicines before these treatments to help lower your risk of CRS. Be sure to contact your cancer care team right away if you have any symptoms that might be from CRS.

Antibodies that target CD19

The CD19 antigen is a protein on the surface of B lymphocytes. Tafasitamab (Monjuvi) is an antibody that targets this protein. It is used as part of treatment for NHL in certain situations.

Tafasitamab (Monjuvi) can be used along with other medicines to treat NHL that has come back or is no longer responding to other treatments.

This drug is infused into a vein (IV). It is typically given about once a week for the first few months, and then once every 2 weeks.

Possible side effects

Some people have an infusion reaction while getting this drug. This can cause symptoms like chills, flushing, headache, or shortness of breath during the infusion. You’ll likely get medicines before treatment to help lower this risk, but it’s important to tell your cancer care team right away if you have any of these symptoms.

Other side effects can include feeling tired or weak, loss of appetite, diarrhea, cough, fever, swelling in the hands or legs, and low blood cell counts with an increased risk of bleeding and serious infection.

Antibody-drug conjugates that target CD19 antibody

An antibody-drug conjugate (ADC) is a monoclonal antibody linked to a chemotherapy drug. In this case, the antibody acts like a homing device. It attaches to the CD19 protein on lymphoma cells and brings the chemo directly to them.

This ADC is used by itself to treat some types of large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL). It may be used after at least 2 other treatments have been tried, not including surgery or radiation.

It is given in a vein (IV) every 3 weeks.

Possible side effects

Common side effects include abnormal liver function tests, low blood counts, feeling tired, rash, nausea, and muscle and joint pain.

More serious side effects include infection, very low blood counts, very severe skin reactions when out in the sun, and fluid collection in the lungs, around the heart, or in the abdomen (belly).

Antibody-drug conjugates with CD30 antibody

Brentuximab vedotin (Adcetris) is an anti-CD30 antibody attached to a chemotherapy drug. The antibody brings the chemo drug to lymphoma cells that have the CD30 antigen.

It can be used to treat:

  • Some types of T-cell lymphoma, either as the first treatment (typically along with chemo) or if the lymphoma comes back after other treatments.
  • Some types of large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL), when the lymphoma has grown or comes back after other drug treatments have been tried.

Brentuximab vedotin is infused into a vein (IV), typically once every 3 weeks.

Possible side effects

Common side effects can include nerve damage (neuropathy), low blood counts, fatigue, fever, nausea and vomiting, infections, diarrhea, and cough.

Antibody-drug conjugates that target CD79b

Polatuzumab vedotin (Polivy) is an anti-CD79b antibody attached to a chemotherapy drug. The antibody brings the chemo drug to lymphoma cells that have the surface protein CD79b.

This drug can be used along with chemo and rituximab to treat diffuse large B-cell lymphoma (DLBCL).

It is infused into a vein (IV), typically every 3 weeks.

Possible side effects

Common side effects can include numbness or tingling of hands/feet (neuropathy), low blood counts, fatigue, fever, decreased appetite, diarrhea, and pneumonia.

Antibodies that target 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.

Possible side effects

The most common side effects are:

  • Fever
  • Chills
  • Nausea
  • Rashes

Risk of infection: This drug can also cause very low white blood cell counts, which increases the risk of serious infections. You will get antibiotic and anti-viral medicines to help protect against infection, but severe and even life-threatening infections can still happen.

Rare but serious side effects can include strokes, as well as tears in the blood vessels in the head and neck.

Possible side effects of these drugs

See the information on each individual drug (above) for a list of its possible side effects.

Immune checkpoint inhibitors

An important part of your immune system is its ability to keep itself from attacking healthy cells in your body. To do this, it uses “checkpoint” proteins. These proteins act like switches on immune cells that need to be turned on or off to start an immune response. Cancer cells sometimes use these checkpoints to avoid being attacked by the immune system.

Immune checkpoint inhibitors work by blocking these checkpoints. This can boost your body’s immune response against cancer cells.

Pembrolizumab (Keytruda) can be used to treat primary mediastinal large B-cell lymphoma (PMBCL) that has come back or not responded to other treatments.  

This drug is infused into a vein (IV), typically every 3 or 6 weeks.

Possible side effects

Side effects can include fatigue, cough, nausea, itching, skin rash, loss of appetite, constipation, joint pain, and diarrhea.

More serious side effects, such as infusion reactions and autoimmune reactions, happen less often. To learn more, see Immune Checkpoint Inhibitors and Their Side Effects.

Possible side effects of these drugs

See the information on each individual drug (above) for a list of its possible side effects.

Immunomodulating drugs

Immunomodulating drugs are thought to work against certain cancers by affecting parts of the immune system. Exactly how these drugs work isn’t clear.

This drug is sometimes used to help treat certain types of lymphoma, usually after other treatments have been tried. It can be given with or without rituximab, or along with tafasitamab.

It is taken daily as pills.

Possible side effects

Side effects can include low white blood cell counts with an increased risk of infection, as well as painful nerve damage (neuropathy). This nerve damage 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.

Risk of severe birth defects 

This drug can cause severe birth defects if taken during pregnancy. You may not be able to take it if there is a chance you might be pregnant or might become pregnant during treatment.

Possible side effects of these drugs

See the information on each individual drug (above) for a list of its possible side effects.

Chimeric antigen receptor (CAR) T-cell therapy

For this treatment, immune cells called T cells are removed from your blood. The cells are then altered in the lab to have receptors called chimeric antigen receptors (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 put back into your blood. They can now seek out the lymphoma cells and launch a precise immune attack against them.

Axicabtagene ciloleucel, also known as axi-cel, is a type of CAR T-cell therapy approved to treat people with:

  • Large B-cell lymphoma if the cancer has not responded to initial treatment with chemotherapy plus immunotherapy, or if it comes back within a year of this treatment. Large B-cell lymphomas are a group of fast-growing NHL subtypes, including diffuse large B-cell lymphoma.
  • Follicular lymphoma or large B-cell lymphoma after at least 2 other kinds of treatment have been tried.

After at least 2 other kinds of treatment have been tried, tisa-cel is approved to treat people with:

  • Diffuse large B-cell lymphoma
  • High-grade B-cell lymphoma
  • Diffuse large B-cell lymphoma arising from follicular lymphoma

Follicular lymphoma that hasn’t responded to or has come back after other therapies

After other kinds of treatment have been tried, liso-cel is approved to treat adults with:

  • Diffuse large B-cell lymphoma
  • Primary mediastinal large B-cell lymphoma
  • High-grade B-cell lymphoma
  • Follicular lymphoma
  • Mantle cell lymphoma
  • Marginal zone lymphoma
  • Small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL)

It is also approved as a second-line treatment for large B-cell lymphoma that has not responded to or has relapsed within 12 months of first-line chemoimmunotherapy.

Brexu-cel is approved to treat adults with mantle cell lymphoma that has come back or is no longer responding to other treatments.

Possible side effects of CAR T-cell therapy  

CAR T-cell therapy can have serious side effects. It is only given in medical centers that have special training with this treatment.

Cytokine release syndrome (CRS): CRS is a serious side effect in which immune cells in the body release large amounts of chemicals into the blood. Symptoms of this life-threatening syndrome can include fever, chills, headache, nausea and vomiting, trouble breathing, very low blood pressure, a very fast heart rate, swelling, diarrhea, feeling very tired or weak, and other problems. 

Immune effector cell-associated neurotoxicity syndrome (ICANS): ICANS is a serious nervous system side effect. Symptoms can include confusion, trouble speaking or understanding others, seizures, tremors, or changes in consciousness.

Other serious side effects can include:

  • Severe infections
  • Low blood cell counts
  • A weakened immune system

To learn more about this treatment and its possible side effects, see CAR T-Cell Therapy.

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.

side by side logos for American Cancer Society and American Society of Clinical Oncology

Developed by the American Cancer Society medical and editorial content team with medical review and contribution by the American Society of Clinical Oncology (ASCO).

National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: B-cell Lymphomas. Version 3.2026. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf on May 4, 2026.

National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Version 2.2026. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/cll.pdf on May 4, 2026.

National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: T-cell Lymphomas. Version 2.2026. Accessed at https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf on May 4, 2026.

Last Revised: October 12, 2026

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

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