Targeted Therapy for Chronic Lymphocytic Leukemia

Targeted therapies are newer 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 attack one or more specific targets on or in chronic lymphocytic leukemia (CLL) cells. They've changed the way CLL is treated because these drugs can often control CLL, so people don't need to start chemo right away.

Kinase inhibitors

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.

Ibrutinib (Imbruvica®)

This targeted drug blocks the activity of a protein called a kinase that tells the CLL cells to divide and helps them survive. This drug has 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.

PI3K inhibitors

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

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 (prophylaxis) anti-infectives 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.

Venetoclax (Venclexta®)

Venetoclax targets BCL-2, a protein in CLL cells that helps them survive longer than they should. This drug is typically used after at least one other treatment has been tried. 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 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.

For more information, see Targeted Therapy.

The American Cancer Society medical and editorial content team
Our team is made up of doctors and master's-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

American Society of Clinical Oncology. Leukemia - Chronic Lymphocytic - CLL: Treatment Options. 06/2016. Accessed at www.cancer.net/cancer-types/leukemia-chronic-lymphocytic-cll/treatment-options on April 17, 2018.

Boddy CS, Ma S. Frontline Therapy of CLL: Evolving Treatment Paradigm. Curr Hematol Malig Rep. 2018;13(2):69-77.

National Comprehensive Cancer Network, Clinical Practice Guidelines in Oncology (NCCN Guidelines®), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 5.2018 -- March 26, 2018. Accessed at www.nccn.org/professionals/physician_gls/pdf/cll.pdf on April 17, 2018.

O'Reilly A, Murphy J, Rawe S, Garvey M. Chronic Lymphocytic Leukemia: A Review of Front-line Treatment Options, With a Focus on Elderly CLL Patients. Clin Lymphoma Myeloma Leuk. 2018;18(4):249-256.  

Last Medical Review: May 10, 2018 Last Revised: June 11, 2018

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