Targeted therapy for chronic lymphocytic leukemia

Last medical review:

Targeted therapy uses drugs to target specific molecules (such as proteins) on cancer cells or inside them. These molecules help send signals that tell cells to grow or divide. By targeting these molecules, the drugs stop the growth and spread of cancer cells and limit harm to normal cells. Targeted therapy may also be called molecular targeted therapy.

If you have targeted therapy, your healthcare team will use what they know about the cancer and about your health to plan the drugs, doses and schedules. Some targeted therapy drugs are taken for a limited time only (called time-limited treatment). Others may be taken for as long as they are effective and you're able to handle any side effects (called continuous treatment).

Targeted therapy is usually used if the chronic lymphocytic leukemia (CLL) cells have any of these molecular characteristics:

  • del(17p), which is often described as a 17p deletion or a 17p chromosome deletion (the short arm "p" of chromosome 17 is missing)
  • TP53 mutation (the TP53 gene has changed and is no longer working properly)
  • unmutated IGHV (the IGHV gene has not changed)

When choosing which targeted therapy drugs would be best for you, your healthcare team considers:

  • if you have any medical conditions, specifically heart or kidney problems
  • if you are willing and if it is safe for you to be on continuous treatment, or if time-limited treatment would be best
  • if there are any barriers to frequent blood work to monitor the cancer and the side effects of the drugs

Different types of targeted therapy are used for CLL. These include:

  • monoclonal antibodies
  • Bruton's tyrosine kinase (BTK) inhibitors
  • BCL2 inhibitors

Side effects of targeted therapy will depend mainly on the type of drug or combination of drugs, the dose, how it's given and your overall health. Tell your healthcare team if you have side effects that you think are from targeted therapy. The sooner you tell them of any problems, the sooner they can suggest ways to help you deal with them.

Monoclonal antibodies

Monoclonal antibodies have been designed in a lab to recognize and lock onto particular protein markers on the surface of some cancer cells. Then they stimulate the body's immune system to attack and destroy the cells they attach to.

Monoclonal antibodies can be used in combination with chemotherapy or other targeted therapy drugs. They may be used as first-line therapy, if the cancer returns after it was treated (called relapsed CLL) or if the cancer did not respond to treatment (called refractory CLL).

Rituximab (Rituxan and biosimilars) targets the CD20 protein on the surface of B lymphocytes. It is one of the main monoclonal antibodies used to treat CLL either as first-line therapy or a part of treatment for relapsed or refractory CLL. Rituximab is given through a needle into a vein (intravenously).

Obinutuzumab (Gazyva) targets the CD20 protein on the surface of B lymphocytes. This monoclonal antibody is often combined with a chemotherapy drug called chlorambucil (Leukeran) to treat CLL as first-line therapy for people who are older and have other health problems. It may also be combined with another targeted therapy drug called venetoclax (Venclexta). Obinutuzumab is given through a needle into a vein (intravenously).

Side effects of monoclonal antibodies

Rituximab and obinutuzumab may cause these side effects:

Bruton's tyrosine kinase (BTK) inhibitors

Bruton's tyrosine kinase (BTK) inhibitors are a type of tyrosine kinase inhibitor. Tyrosine kinases are a part of a protein that acts like a cell's on and off switch. They are enzymes that play an important role in a cell's growth and division. Tyrosine kinase inhibitors block these enzymes from sending signals that cause a cancer cell to grow.

BTK inhibitors may be used alone or in combination with chemotherapy or other targeted therapy drugs. They may be used as a first-line therapy or in relapsed or refractory CLL. BTK inhibitors are considered to be continuous treatment, meaning that you keep taking these medicines until the CLL no longer responds to them or you have to stop taking them because of the side effects. They are capsules or tablets given by mouth. You also don't need to have frequent clinic visits when taking these drugs.

Ibrutinib (Imbruvica) is a BTK inhibitor that is often used to treat CLL with a 17p chromosome deletion, a TP53 gene mutation or an unmutated IGHV gene.

Acalabrutinib (Calquence) is a BTK inhibitor that may also be used to treat CLL with a 17p chromosome deletion, a TP53 gene mutation or an unmutated IGHV gene. Acalabrutinib may not be covered by all provincial or territorial health plans.

Zanubrutinib (Brukinsa) is a BTK inhibitor that may be used to treat CLL. Zanubrutinib may not be covered by all provincial or territorial health plans.

Side effects of BTK inhibitors

Ibrutinib, acalabrutinib and zanubrutinib may cause these side effects:

BCL2 inhibitors

BCL2 is a protein on CLL cells that helps them survive. BCL2 inhibitors target that protein to stop it from working so the CLL cell dies more quickly.

Venetoclax (Venclexta) is a BCL2 inhibitor that may be used alone or in combination with rituximab or obinutuzumab to treat CLL. It can be given as a first-line therapy or for relapsed or refractory CLL. Venetoclax is a tablet given by mouth. If venetoclax is given on its own, you will have this treatment for as long as it is effective or until you experience side effects that you can't manage (called continuous treatment). If it is combined with obinutuzumab, the treatment is for 1 year (called time-limited treatment). If it is combined with rituximab, the treatment is for 2 years.

Side effects of BCL2 inhibitors

Venetoclax has an increased risk of tumour lysis syndrome. Drinking plenty of water to stay hydrated will help manage this risk. You will be closely monitored through frequent blood work and will have weekly visits to the doctor. To help prevent tumour lysis syndrome, venetoclax is given at a low dose to begin and the amount is slowly increased until you safely get the required amount. This is called ramp-up dosing.

Venetoclax may cause these side effects:

Find out more about targeted therapy

Find out more about targeted therapy. To make the decisions that are right for you, ask your healthcare team questions about targeted therapy.

Details on specific drugs change regularly. Find out more about sources of drug information and where to get details on specific drugs.

Expert review and references

  • Versha Banerji, MD, FRCPC
  • Guideline Resource Unit. Chronic Lymphocytic Leukemia. Version 8 ed. Edmonton: Alberta Health Services; 2023:
  • American Cancer Society . Treating Chronic Lymphocytic Leukemia . 2018 :
  • The Canadian Agency for Drugs and Technologies in Health. CADTH Reimbursement Review Provisional Funding Algorithm Chronic Lymphocytic Leukemia. 2021:
  • Chronic Lymphocytic Leukemia Clinic. Practice Guideline: Disease Management Consensus Recommendations for the Management of Chronic Lymphocytic Leukemia. Winnipeg, MB: CancerCare Manitoba; 2015.
  • Wierda WG, O'Brien SM. Chronic lymphocytic leukemias. DeVita VT Jr., Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology. 11th ed. Philadelphia, PA: Wolters Kluwer; 2019: Kindle version, ch 105,
  • Muhsin Chisti M. Medscape Reference: Chronic Lymphocytic Leukemia (CLL) Treatment and Management. WebMD LLC; 2020:
  • PDQ® Adult Treatment Editorial Board. Chronic Lymphocytic Leukemia Treatment (PDQ®) – Health Professional Version. Bethesda, MD: National Cancer Institute; 2021:
  • National Comprehensive Cancer Network . NCCN Clinical Practice Guidelines in Oncology: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (Version 2.2022) . 2022 .
  • Owen C, Banerji V, Johnson N, et al. Canadian evidence-based guideline for frontline treatment of chronic lymphocytic leukemia: 2022 update. Leukemia Research. 2023: 125:107016.
  • Owen C, Eisinga S, Banerji V, et al. Canadian evidence-based guideline for treatment of relapsed/refractory chronic lymphocytic leukemia. Leukemia Research. 2023: 133:107372.

Medical disclaimer

The information that the Canadian Cancer Society provides does not replace your relationship with your doctor. The information is for your general use, so be sure to talk to a qualified healthcare professional before making medical decisions or if you have questions about your health.

We do our best to make sure that the information we provide is accurate and reliable but cannot guarantee that it is error-free or complete.

The Canadian Cancer Society is not responsible for the quality of the information or services provided by other organizations and mentioned on, nor do we endorse any service, product, treatment or therapy.

1-888-939-3333 | | © 2024 Canadian Cancer Society