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 the patient's immune system react and destroy the cancer cells.

Rituximab

Rituximab (Rituxan) is a monoclonal antibody that targets the CD20 antigen, which is found on the surface of B lymphocytes. It 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.

Rituximab is given by injection into a vein (IV), usually once a week. It can also be given once a month or every few months. Common side effects are usually mild but may include chills, fever, nausea, rashes, fatigue, and headaches. Rarely, more severe side effects occur during infusions (while the drug is being given), such as trouble breathing and low blood pressure. Even if these symptoms occur during the first rituximab infusion, it is very unusual for them to recur with later doses. Rituximab can cause hepatitis B infections that were dormant (inactive) to become active again, sometimes leading 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. This drug may also increase a person's risk of certain infections for many months after the drug is stopped.

In rare cases of patients with very high white blood cell counts, the drug 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.

Alemtuzumab

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 in patients with CLL that 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 if the patient has large 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. 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.

Ofatumumab

Ofatumumab (Arzerra^®) is another monoclonal antibody that targets the CD20 antigen. It is used mainly in patients with CLL that is no longer responding to other treatments such as chemotherapy or alemtuzumab.

Ofatumumab is given by injection into a vein (intravenous or IV) over several hours. The standard course is once a week for 8 weeks, followed by once a month for 4 months. Infusion reactions, including fever, chills, nausea, swelling, blood pressure changes, and rashes, are common during the infusion, so medicines are given beforehand to try to lower this risk. This drug can increase a person's risk of infections. Other side effects are less common but are potentially serious, including low platelet counts (with increased risk of bleeding) and blockage (obstruction) of the intestines.