Targeted Therapy Drugs for Chronic Lymphocytic Leukemia

Targeted therapies are drugs that specifically target some of the changes inside cancer cells that help them grow. 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. When treatment is needed for CLL, a targeted drug is often part of the first line of treatment.

Bruton's tyrosine kinase (BTK) inhibitors

BTK is a protein that normally helps some CLL cells to grow and survive. Drugs that target this protein, known as BTK inhibitors, can be helpful in treating CLL.

Ibrutinib (Imbruvica)

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 daily as a pill.

Side effects 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.

Acalabrutinib (Calquence)

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.

Zanubrutinib (Brukinsa)

Zanubrutinib can be used in the initial treatment of CLL, or after other treatments have been tried. This drug is taken by mouth as pills, typically once or twice a day. 

Side effects can include low white blood cell count (with an increased risk of infection), low blood platelet count (with an increased risk of bleeding and bruising), upper respiratory infections, muscle and joint pain, feeling tired, headache, cough, skin rash, and diarrhea. More serious side effects can include bleeding (hemorrhage), serious infections, and heart rhythm problems. 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.

Pirtobrutinib (Jaypirca)

Pirtobrutinib can be used to treat CLL, typically after at least 2 other treatments (including another BTK inhibitor and a BCL-2 inhibitor) have been tried. This drug is taken by mouth as pills, typically once a day.

Common side effects can include diarrhea, bruising, feeling tired, muscle and joint pain, cough, and low blood cell counts. Less common but more serious side effects can include bleeding (hemorrhage), serious infections, and heart rhythm problems. 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 inhibitors

Phosphatidylinositol 3-kinases (PI3Ks) are a family of proteins that send signals in cells that can affect cell growth. Drugs that target these proteins, known as PI3K inhibitors, can be helpful in treating CLL.

Idelalisib (Zydelig)

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 (prophylactic) medicines to help keep this from happening. Your cancer care team will also watch you closely for signs of infection.

Duvelisib (Copiktra)

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, severe skin problems.

BCL-2 inhibitor

BCL-2 is a protein in CL cells that helps them survive longer than they should. Drugs that target this protein, known as BCL-2 inhibitors, can be helpful in treating CLL.

Venetoclax (Venclexta)

Venetoclax 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. It's more common in patients who have large numbers of leukemia cells in their body when treatment starts. (This may be called bulky disease.) When the CLL cells are killed, they break open and release their contents into the bloodstream. This can overwhelm the kidneys to the point that they can't get rid of all of these substances fast enough. This can lead to 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. To help keep this from happening, you may start at a very low dose and then slowly increase it over about 5 weeks. Your treatment team will do blood tests and also watch for signs of TLS.