Chronic Lymphocytic Leukemia

• 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).
• 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.

Targeted therapies are drugs that specifically target the changes inside cells that cause them to become cancer. Unlike standard chemotherapy drugs, which work by attacking rapidly growing cells in general (including cancer cells), these drugs target one or more specific proteins on or in chronic lymphocytic leukemia (CLL) cells.

These drugs block kinases, which are proteins in cells that normally relay signals (such as telling the cell to grow). Many different types of kinases exist, and there are two that are targeted by specific drugs used to treat CLL: Bruton's tyrosine kinase (BTK) and PI3K.

Bruton's tyrosine kinase (BTK) inhibitors

BTK is a protein that normally helps some CLL cells to grow and survive.

This targeted drug blocks the activity of BTK in CLL cells. Ibrutinib can be used in the initial treatment of CLL. It has also been shown to help when CLL is hard to treat, for instance, if there are chromosome 17 deletions or if CLL has come back after other treatments. This drug is taken as a pill.

Side effects tend to be mild, but can include diarrhea, nausea, constipation, fatigue, shortness of breath, swelling of the feet and hands, body aches, and rash. Low blood counts, including low red blood cell counts (anemia), low levels of certain white blood cells (neutropenia), and platelet counts (thrombocytopenia), are also common side effects. Some people treated with this drug get infections which can be serious. There are other side effects, too, so ask your doctor what you can expect.

This targeted drug also blocks the activity of BTK. Acalabrutinib can be used in the initial treatment of CLL, or after other treatments have been tried. It might be used alone or along with other drugs. This drug is taken by mouth as capsules, typically twice a day.

Side effects can include headache, diarrhea, bruising, fatigue, muscle and joint pain, cough, rash, and low blood counts, including low red blood cell counts (anemia), low levels of certain white blood cells (neutropenia), and platelet counts (thrombocytopenia). More serious side effects can include bleeding (hemorrhage), serious infections, and irregular heartbeat (atrial fibrillation). Some people taking this drug have developed skin or other cancers, so it’s important to use sun protection when outside while taking this drug.

PI3K is a protein that sends signals in cells and controls cell growth.

Idelalisib blocks a kinase protein called PI3K-delta. It's been shown to help treat CLL after other treatments have been tried. It's a pill taken twice a day. Common side effects include diarrhea, fever, fatigue, nausea, cough, pneumonia, belly pain, chills, and rash. Low blood counts, including low red blood cell counts (anemia), low levels of certain white blood cells (neutropenia), and platelet counts (thrombocytopenia), are also common. Less often, more serious side effects can occur, such as liver damage, severe diarrhea, lung inflammation (pneumonitis), serious allergic reactions, severe skin problems, and holes (perforations) in the intestines. Old (dormant) infections (like hepatitis) may become active again while talking this drug. You may be given preventive (prophylaxis) anti-infectives to help keep this from happening. Your cancer care team will also watch you closely for signs of infection.

Duvelisib blocks two kinase proteins called PI3K-delta and PI3K-gamma. It's been shown to help treat CLL after other treatments have been tried. It's a pill taken twice a day. Common side effects include diarrhea, fever, fatigue, nausea, cough, pneumonia, belly pain, joint/muscle pain and rash. Low blood counts, including low red blood cell counts (anemia) and low levels of certain white blood cells (neutropenia) are also common. Less often, more serious side effects can occur, such as liver damage, severe diarrhea, lung inflammation (pneumonitis), serious allergic reactions, and severe skin problems.

Venetoclax targets BCL-2, a protein in CLL cells that helps them survive longer than they should. This drug can be used alone or along with a monoclonal antibody, such as rituximab. It's taken as a pill once a day.

Side effects can include low levels of certain white blood cells (neutropenia), low red blood cell counts (anemia), diarrhea, nausea, respiratory infections (such as colds), low platelet counts (thrombocytopenia), and feeling tired. Less common but more serious side effects can include pneumonia and other serious infections. Tumor lysis syndrome (TLS) is another possible side effect of this drug.