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Immunotherapy for Chronic Lymphocytic Leukemia

Immunotherapy is treatment that either boosts the patient’s own immune system or uses lab-made versions of the normal parts of the immune system to kill cancer cells or slow their growth. Some types of immunotherapy can be used to treat chronic lymphocytic leukemia (CLL).

Monoclonal antibodies

Monoclonal antibodies are lab-made versions of immune system proteins (antibodies). Once inside the body, they attach to a specific target (often a protein on the surface of cancer cells). These drugs can help your immune system react to and destroy the cancer cells. Some monoclonal antibodies also fight cancer in other ways.

A monoclonal antibody might be given along with a targeted drug or with chemotherapy (chemo) as part of the treatment for CLL.

The monoclonal antibodies used to treat CLL can be divided based on which protein they target.

Antibodies that target CD20

CD20 is a protein on the surface of B lymphocytes (the cells from which CLL starts). A few monoclonal antibodies used to treat CLL target the CD20 antigen. These drugs include:

  • Rituximab (Rituxan, other names)
  • Obinutuzumab (Gazyva)
  • Ofatumumab (Arzerra)

Rituximab is most often used along with chemotherapy or a targeted drug, either as part of the initial treatment or as part of a second-line treatment, but it may also be used by itself for people too sick to get chemo.

Obinutuzumab can be used along with the chemo drug chlorambucil or with a targeted drug such as ibrutinib (Imbruvica) as a part of the initial treatment for CLL. It can also be used alone for CLL that comes back after treatment or doesn't respond to other treatments.

Ofatumumab is used mainly if CLL is no longer responding to other treatments such as chemotherapy or other monoclonal antibodies such as alemtuzumab (discussed below). It can be given by itself.

Side effects

These drugs are given by infusion 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 afterwards. 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, lightheaded, or 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's given as a shot under the skin (although the first dose must be given IV). It can take 5 to 7 minutes to inject the drug, but this is much shorter than the time it normally takes to give the drug IV. 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 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. For example, rituximab has been linked to a rare brain disease known as progressive multifocal leukoencephalopathy (PML) that's caused by a virus. It can lead to headache, high blood pressure, seizures, confusion, loss of vision, and even death.

In rare cases of patients with very high white blood cell counts, some of these drugs (especially obinutuzumab) may cause a condition called tumor lysis syndrome. 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 most often happens during the first course of treatment. When the CLL cells are killed, they break open and release their contents into the bloodstream. This can overwhelm the kidneys, so they can't get rid of all of these substances fast enough. This can lead to build up of excess amounts of certain minerals in the blood and even kidney failure. The excess minerals can cause problems with the heart and nervous system. Doctors try to keep this from happening by giving the patient extra fluids and certain drugs, such as sodium bicarbonate, allopurinol, febuxostat, and rasburicase.

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

Antibodies that target CD52

Alemtuzumab (Campath) is a monoclonal antibody that targets the CD52 antigen, which is found on the surface of CLL cells and many T lymphocytes. It is used mainly if CLL is no longer responding to standard treatments, but it can also be used earlier in the disease. It may be especially useful for people who have CLL with a chromosome 17 deletion, which is often resistant to standard treatments. In this case, it may be the first treatment used, along with rituximab. Alemtuzumab doesn’t seem to work as well in people with enlarged lymph nodes (2 inches across or larger).

Alemtuzumab is given by injection into a vein (intravenous or IV), usually several times a week. In studies, it has also been given as an injection under the skin (subcutaneously), but giving it this way is not approved by the Food and Drug Administration (FDA).

Side effects

Some people might have an infusion reaction while getting this drug (or shortly afterward). This is like an allergic reaction, and can include fever, chills, flushing of the face, rash, itchy skin, feeling dizzy, wheezing, and trouble breathing. It’s important to tell your doctor or nurse right away if you have any of these symptoms while getting this drug.

This drug can cause very low white blood cell counts, which increases the risk for severe infections. Antibiotic and antiviral medicines are typically given to help protect against some of these infections, but severe and even life-threatening infections can still occur. Old, inactive (dormant) infections can also become active again while taking this drug.

This drug may also cause low red blood cell and platelet counts.

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

To learn more about monoclonal antibodies in general, see Monoclonal Antibodies and Their Side Effects.

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 CLL cells. The T cells are then multiplied in the lab and given back into the patient’s blood, where they can seek out the CLL cells and launch a precise immune attack against them.

Lisocabtagene maraleucel (Breyanzi, also known as liso-cel) can be used to treat adults with CLL that is still growing or that has returned, typically after treatment with at least 2 types of targeted drugs has already been tried.

Side effects of CAR T-cell therapy

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

  • These treatments can sometimes cause cytokine release syndrome (CRS), in which immune cells in the body release large amounts of chemicals into the blood. Symptoms of this 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.  This condition can sometimes even be life-threatening.
  • These treatments can sometimes cause serious neurological (nervous system) problems, such as confusion, trouble speaking, seizures, tremors, or changes in consciousness.
  • Other serious side effects of these treatments can include severe infections, low blood cell counts, and a weakened immune system.

To learn more about this type of treatment, see CAR T-Cell Therapies.

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 editors and translators with extensive experience in medical writing.

Boddy CS, Ma S. Frontline Therapy of CLL: Evolving Treatment Paradigm. Curr Hematol Malig Rep. 2018 Apr;13(2):69-77.

Hallek M, Cheson BD, Catovsky D, et al. Guidelines for diagnosis, indications for treatment, response assessment and supportive management of chronic lymphocytic leukemia. Blood. 2018 Mar 14. pii: blood-2017-09-806398.

National Comprehensive Cancer Network, Clinical Practice Guidelines in Oncology (NCCN Guidelines®), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 5.2018 -- March 26, 2018. Accessed at on April 16, 2018.

O'Reilly A, Murphy J, Rawe S, Garvey M. Chronic Lymphocytic Leukemia: A Review of Front-line Treatment Options, With a Focus on Elderly CLL Patients. Clin Lymphoma Myeloma Leuk. 2018;18(4):249-256.  

Last Revised: March 29, 2024

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