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 and destroy the cancer cells. Some monoclonal antibodies also fight cancer in other ways.

The monoclonal antibodies used to treat chronic lymphocytic leukemia (CLL) can be divided into groups based on which protein they target.

Targeting CD20

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

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

Rituximab is used mainly to treat certain kinds of non-Hodgkin lymphoma, but it has also become one of the main treatments for chronic lymphocytic leukemia (CLL). It is most 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 can be used along with the chemo drug chlorambucil as a part of the initial treatment for CLL.

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).

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 or light headed, 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 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 is caused by a virus. It can lead to headache, high blood pressure, seizures, confusion, loss of vision, and even death.

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.

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 chemotherapy treatments, but it can be used earlier in the disease. It may be especially useful in cases of CLL with a chromosome 17 deletion, which are often resistant to standard treatments, but it doesn’t seem to work as well in people whose lymph nodes are enlarged (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. 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 is 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. It may also cause low red blood cell and platelet counts.

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 master's-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Last Medical Review: January 6, 2015 Last Revised: April 11, 2016

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