Immunotherapy for Chronic Lymphocytic Leukemia (CLL)

Immunotherapy is treatment that either boosts your 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 as a treatment for CLL

Monoclonal antibodies are lab-made versions of immune system proteins (antibodies). Once inside your 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 cancer cells. Some monoclonal antibodies also fight cancer in other ways.

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

The monoclonal antibodies used to treat CLL can be grouped 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). Some monoclonal antibodies that target the CD20 antigen can be used to treat CLL:

• 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 for CLL. 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 as 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 chemotherapy or other treatments, such as monoclonal antibodies like alemtuzumab (discussed below). It can be given by itself.

How these drugs are given

• Infusion into a vein (IV): These drugs are given by infusion into a vein (IV). This can take up to several hours, depending on the drug.
• Injection under the skin: There is also a form of rituximab given as a shot under the skin (although the first dose must be given IV). Injecting the drug in this way takes 5 to 7 minutes. Possible side effects include local skin reactions (like redness) where the drug is injected, infections, low white blood cell counts, nausea, fatigue, and constipation.

Side effects of these drugs

Infusion reactions: When given IV, all of these drugs can cause infusion reactions. Infusion reactions can happen either while the drug is being given or several hours afterward. These can be mild, such as itching, chills, fever, nausea, rashes, fatigue, and headaches.

More serious infusion reactions can also occur, leading to problems such as:

• Chest pain
• Racing heart
• 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.

Hepatitis B virus (HBV) reactivation: All of these drugs can cause dormant (inactive) HBV infections to become active again. This can lead to severe liver problems or even death.

For this reason, your cancer care team may check your blood for signs of an old HBV infection before starting this drug. If your blood shows signs of an old HBV infection, they will check your blood during treatment to see if the virus becomes active again. If it does, the drug will need to be stopped.

Increased risk of infections: These drugs may increase your risk of certain serious infections for many months after treatment is stopped.

For example, treatment with one of these drugs can lead to a rare brain disease known as progressive multifocal leukoencephalopathy (PML), which is caused by a virus. This rarely happens, but when it does, it can lead to headaches, high blood pressure, seizures, confusion, loss of vision, and even death.

Tumor lysis syndrome: Rarely, when people with CLL have very high white blood cell counts, these drugs (especially obinutuzumab) may cause a condition called tumor lysis syndrome. This 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. The kidneys can be overwhelmed to the point that they can't get rid of these substances fast enough. This can lead to a 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 prevent this by giving extra fluids and certain drugs, such as sodium bicarbonate, allopurinol, febuxostat, and rasburicase.

Other side effects: Other side effects can occur, depending on which drug you are given. Ask your cancer care team what you can expect.

Antibodies that target CD52

The CD52 antigen is found on the surface of CLL cells and many T lymphocytes.

Alemtuzumab is a monoclonal antibody that targets the CD52 antigen. It is mainly used if CLL is no longer responding to standard treatments, but it can also be used earlier in the disease.

Alemtuzumab may be especially useful for people who have CLL with a chromosome 17 deletion, which is often resistant to standard treatments. It 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.

Side effects of alemtuzumab

Infusion reactions: Some people might have an infusion reaction while getting this drug (or shortly afterward). This is like an allergic reaction. It can include fever, chills, flushing of the face, rash, itchy skin, dizziness, wheezing, and trouble breathing.

It’s important to tell your cancer care team right away if you have any of these symptoms while getting this drug.

Very low white blood cell counts (risk of severe infection): This drug can cause very low white blood cell counts, increasing 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 happen. Dormant infections can also become active again when you take this drug.

Other side effects: 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 as a treatment for CLL

In this treatment, immune cells called T cells are removed from  your 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 altered T cells are then multiplied in the lab and given back into your 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) is a type of CAR T-cell therapy that can be used to treat adults with CLL that is still growing or that has returned. It is typically used after treatment with 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 at medical centers with special training in this treatment.

Cytokine release syndrome (CRS): CRS happens when immune cells in your body release large amounts of chemicals into your blood. It can be life-threatening.

Symptoms 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.

Serious neurological (nervous system) problems, including:

• Confusion
• Trouble speaking
• Seizures
• Tremors
• Changes in consciousness

Other serious side effects, including:

• Severe infections
• Low blood cell counts
• A weakened immune system

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