Immunotherapy for Castleman Disease

Immunotherapy is treatment that either boosts the patient’s own immune system or uses man-made versions of the normal parts of the immune system.

Monoclonal antibodies

Antibodies are proteins made by the body’s immune system to help fight infections. Man-made versions, called monoclonal antibodies, can be designed to attack a specific target, such as a substance on the surface of lymphocytes, the cells in which Castleman disease (CD) starts. Sometimes they are given along with chemotherapy.

Siltuximab (Sylvant): This monoclonal antibody is used to treat some patients with multicentric CD. These patients often have high levels of a protein called IL-6. Siltuximab binds to IL-6, which keeps the protein from acting on lymphocytes. This drug doesn’t seem to bind to IL-6 that is made from viruses, so it isn’t meant for patients who are infected with either HIV or HHV-8. (IL-6, HIV, and HHV-8 were discussed in What Causes Castleman Disease?)

This drug is given as an infusion into a vein (IV), usually every 3 weeks.

Side effects tend to be mild and can include rash, itching, swelling, and weight gain. Some patients can also have side effects during the infusion, such as flushing (skin redness with a feeling of warmth), chest pain, back pain, nausea, and rapid heartbeat.

Rituximab (Rituxan): This monoclonal antibody is used widely for lymphoma. It can also be helpful in treating CD. Rituximab attaches to a protein called CD20 that is found on the surface of some lymphocytes. This attachment causes the cell to die.

Side effects of rituximab are most common during the infusion, and can include chills, fever, nausea, rashes, fatigue, and headaches. Rarely, more severe side effects occur during the infusion, such as trouble breathing and low blood pressure. Unlike regular chemotherapy, rituximab does not cause low blood counts or hair loss.

This drug can also increase a person’s risk of certain infections. In people who have ever been infected with the hepatitis B virus, this drug can sometimes cause the infection to become active again. Your doctor may check your blood for signs of a prior hepatitis infection before starting this drug to see if it is safe.

Tocilizumab (Actemra): This monoclonal antibody is used to treat some kinds of arthritis that can affect the immune system. Tocilizumab works by blocking certain messenger proteins, known as cytokines, that send signals between some cells of the immune system. Tocilizumab is sometimes used in unicentric and multicentric CD after other treatments have stopped working.

Side effects of tocilizumab include runny or stuffy nose, sinus pain, sore throat, headache, dizziness, itching, mild stomach cramps, or urinary tract infection (UTI). This drug also increases the risk for developing serious infections. Your doctor will monitor you closely during treatment.

Rituximab and tocilizumab are drugs that are given through infusion into a vein (IV) at the doctor’s office or clinic.

Other antibodies: Newer antibodies that attack other targets are also being studied for use against CD. These are discussed in What’s New in Research of Castleman Disease?

Immunomodulating drugs (IMiDs)

Drugs such as thalidomide (Thalomid) and lenalidomide (Revlimid) are used to treat certain cancers of immune cells such as multiple myeloma and some types of lymphoma, but they have also helped some patients with CD.

These drugs are thought to work by affecting parts of a person’s immune system. It’s not exactly clear how they do this, but it seems to be at least in part by working against interleukin-6 (IL-6).

The drugs can cause side effects such as drowsiness, fatigue, constipation, low blood cell counts, and neuropathy (painful nerve damage). There is also an increased risk of serious blood clots (that start in the leg and can travel to the lungs). These tend to be more likely with thalidomide.

Because of concerns these drugs can cause severe birth defects if taken during pregnancy, they can only be obtained through special programs run by the drug company that makes them.

Interferon-alfa

Interferon-alfa is a hormone-like protein made by white blood cells in the body to help the immune system fight infections. Some patients with CD have improved with man-made interferon treatment.

Interferon is given by an injection, either daily or several times a week. This may be into a vein (IV), under the skin (SubQ), or into a muscle (IM). It may be given in a doctor’s office, or you or a family member can be taught how to give the medicine under the skin.

Side effects of this treatment can include fatigue, fever, chills, headaches, muscle and joint aches, and mood changes. Because of its side effects, interferon is not used very often. It may be given to some patients in addition to chemotherapy.