Monoclonal Antibodies for Chronic Lymphocytic Leukemia

Monoclonal antibodies are man-made versions of immune system proteins (antibodies) that are designed to attach to a specific target (in this case, proteins 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.

Chemo given along with a monoclonal antibody is a standard treatment for chronic lymphocytic leukemia (CLL).

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

Targeting CD20

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

  • Rituximab (Rituxan)
  • Obinutuzumab (Gazyva)
  • Ofatumumab (Arzerra)

Rituximab has become one of the main treatments for CLL. It's 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 the targeted drug 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 5-7 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 what you can expect.

Targeting 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 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, given 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

The most common side effects are fever, chills, nausea, and rashes during the injection, but these effects seem to be less of a problem when it's given under the skin. It can also cause very low white blood cell counts, which increases the risk for severe bacterial and viral infections. Antibiotic and antiviral medicines are given to help protect against some of these infections, but severe and even life-threatening infections can still occur. As discussed above, old (dormant) infections can also become active again while taking this drug. It may cause low red blood cell and platelet counts, too. Your doctor will watch for these problems. Rare but serious side effects can include strokes, as well as tears in the blood vessels in the head and neck.

Targeting CD22 (to treat hairy cell leukemia)

CD22 is another protein found on B lymphocytes. Lumoxiti (moxetumomab pasudotox) is a type of drug known as an antibody-drug conjugate. It’s made up of an antibody that targets the CD22 antigen, linked to a toxin that can kill cancer cells. The antibody acts like a homing device, bringing the toxin directly to the leukemia cells.

This drug is used to treat hairy cell leukemia (HCL), typically after other treatments have been tried.

Side effects

Like other monoclonal antibodies, this drug can cause side effects during the infusion (while the drug is being given) or several hours afterwards. These are usually mild, such as itching chills, fever, nausea, rashes, fatigue, and headaches, but sometimes they can be more serious. You might be given medicines before each infusion to help prevent these problems.

Other side effects can include:

  • Swelling (edema) caused by excess fluid in body tissue
  • Nausea
  • Feeling tired
  • Headache
  • Fever
  • Constipation
  • Diarrhea
  • Low levels of red blood cells (anemia)
  • Changes in levels of electrolytes in the blood 

Other, more serious side effects are also possible:

Capillary leak syndrome is a condition in which fluid and proteins leak out of tiny blood vessels and into surrounding tissues. Symptoms can include:

  • Trouble breathing
  • Cough
  • Weight gain
  • Low blood pressure, which might make you feel dizzy or faint
  • Swelling in the arms, legs, or face

This condition can be life-threatening if not treated, so it’s important to call your doctor right away if you have any of these symptoms. 

Hemolytic uremic syndrome is a condition caused by the destruction of red blood cells. It can result in low levels of red blood cells, kidney damage, and damage to some other organs. Symptoms can include:

  • Peeing less often and having dark-colored urine
  • Bleeding or bruising easily
  • Belly pain
  • Vomiting
  • Fever
  • Shortness of breath
  • Feeling tired or confused

You will be told to drink a lot of fluids during treatment to help prevent this problem. This condition can be life-threatening if not treated, so it’s important to call your doctor right away if you have any of these symptoms.

You can learn more about monoclonal antibodies in Immunotherapy.

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.

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: May 20, 2019

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