First-line therapy for chronic lymphocytic leukemia

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The most common treatments used as first-line therapy for chronic lymphocytic leukemia (CLL) are targeted therapy and chemoimmunotherapy.

Targeted therapy uses drugs to target specific molecules (such as proteins) on cancer cells or inside them to stop the growth and spread of cancer. Chemoimmunotherapy combines chemotherapy with monoclonal antibodies, which are a type of targeted therapy. Chemotherapy uses drugs to destroy cancer cells.

Your healthcare team will suggest treatments based on the molecular characteristics of the CLL cells. Your age and your overall health may also matter. What you want will also be important when planning your treatment.

CLL with del(17p) or TP53 mutation

First-line therapy if you have CLL that has a 17p chromosome deletion (the short arm "p" of chromosome 17 is missing) or a TP53 gene mutation (the TP53 gene has mutated, or changed) is usually targeted therapy.

The most common targeted therapy drugs that are offered are:

  • acalabrutinib (Calquence)
  • ibrutinib (Imbruvica)
  • VO – venetoclax (Venclexta) and obinutuzumab (Gazyva)

CLL without del(17p) or TP53 mutation

First-line therapy if you have CLL that doesn't have a 17p chromosome deletion or a mutation to the TP53 gene is targeted therapy or chemoimmunotherapy. Your healthcare team's recommendation will depend on whether the IGHV gene is unmutated or mutated, your age and overall health.

Unmutated IGHV

If the IGHV gene is unmutated (the IGHV gene has not changed) and you are younger than 65 years old and in good overall health, you will be offered targeted therapy for first-line therapy. The targeted therapy drug or drug combinations include:

  • acalabrutinib (Calquence)
  • ibrutinib (Imbruvica)
  • VO – venetoclax (Venclexta) and obinutuzumab (Gazyva)

These targeted therapy drugs may not be covered by all provincial or territorial health plans.

If the IGHV gene is unmutated and you are older than 65 or your overall health is poor, you will be offered targeted therapy for first-line therapy. The targeted therapy drug or drug combinations are:

  • acalabrutinib (Calquence)
  • VO – venetoclax (Venclexta) and obinutuzumab (Gazyva)

These targeted therapy drugs may not be covered by all provincial or territorial health plans.

Find out more about targeted therapy for CLL.

Mutated IGHV

If the IGHV gene is mutated and you are younger than 65 years old and in good overall health, the most common first-line therapy is FCR, which is a type of chemoimmunotherapy. This combines fludarabine (Fludara), cyclophosphamide (Procytox) and rituximab (Rituxan and biosimilars).

Another treatment option that you may be offered is VO, which is a combination of 2 targeted therapy drugs called venetoclax (Venclexta) and obinutuzumab (Gazyva).

If the IGHV gene is mutated and you are older than 65 or your overall health is poor, the first-line therapy is either targeted therapy or chemoimmunotherapy.

The most common targeted therapy drugs are:

  • VO – venetoclax and obinutuzumab
  • acalabrutinib (Calquence) (may not be covered by all provincial or territorial health plans)

The most common chemoimmunotherapy drug combinations are:

  • BR – bendamustine (Treanda, Benvyon, Esamuze) and rituximab (Rituxan and biosimilars)
  • obinutuzumab and chlorambucil (Leukeran)

Clinical trials

You may be asked if you want to join a clinical trial for CLL. Clinical trials look at new ways to prevent, find and treat cancer. Find out more about clinical trials.

If you can't have or don't want cancer treatment

You may want to consider a type of care to make you feel better without treating the cancer itself. This may be because the cancer treatments don't work anymore, they're not likely to improve your condition or they may cause side effects that are hard to cope with. There may also be other reasons why you can't have or don't want cancer treatment.

Talk to your healthcare team. They can help you choose care and treatment for advanced cancer.

Expert review and references

  • Versha Banerji, MD, FRCPC
  • Guideline Resource Unit. Chronic Lymphocytic Leukemia. Version 8 ed. Edmonton: Alberta Health Services; 2023: https://www.albertahealthservices.ca/.
  • The Canadian Agency for Drugs and Technologies in Health. CADTH Reimbursement Review Provisional Funding Algorithm Chronic Lymphocytic Leukemia. 2021: https://cadth.ca/.
  • Chronic Lymphocytic Leukemia Clinic. Practice Guideline: Disease Management Consensus Recommendations for the Management of Chronic Lymphocytic Leukemia. Winnipeg, MB: CancerCare Manitoba; 2015.
  • Hallek M, Cheson BD, Catovsky D, et al. iwCLL guideline for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. American Society of Hematology; 2018: 131(25):2745–2760.
  • 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, https://read.amazon.ca/?asin=B0777JYQQC&language=en-CA.
  • 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.

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