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Targeted therapies are drugs that specifically focus on 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 the CLL cells have a chromosome 17 deletion (del17p) or if the CLL has come back after other treatments. This drug is a pill taken daily.

Side effects of ibrutinib can include diarrhea, nausea, constipation, fatigue, shortness of breath, swelling of the feet and hands, body aches, and rash. Low red blood cell counts (anemia), and low levels of certain white blood cells (neutropenia) and platelets (thrombocytopenia) are also common side effects. Some people treated with this drug get serious infections. Other side effects are also possible, so ask your doctor what you might 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 a capsule taken by mouth, typically twice a day. 

Side effects of acalabrutinib 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 while taking this drug, it’s important to use sun protection when outside.

Zanubrutinib (Brukinsa)

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

Side effects of zanubrutinib can include a low white blood cell count (with an increased risk of infection), low 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 is a newer type of BTK inhibitor that works in a slightly different way. It can be used to treat CLL, typically after 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 o?f pirtobrutinib 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 cancer or other cancers, so while taking this drug, it’s important to protect yourself from the sun when outside.

BCL-2 inhibitors

BCL-2 is a protein in CLL cells that helps them live 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 or obinutuzumab. It's taken as a pill, typically once a day.

Side effects of venetoclax 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 people 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. The kidneys can be overwhelmed 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, your doctor may start you on venetoclax 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.

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, typically taken twice a day.

Common side effects of idelalisib 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 when someone is takes 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, typically 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 red blood cells (anemia) and 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.