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Current and Next-Gen Treatments for Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is a type of cancer that affects the bone marrow and blood. It is also known as B-cell chronic lymphocytic leukemia because it develops from a type of white blood cell known as B-cells. This is a slowly progressing cancer that typically affects older adults. Because this cancer is slow-growing, most people with the illness do not need to begin treatment for several years after being diagnosed.

Current and Next-Gen Treatments for Chronic Lymphocytic Leukemia

However, once cancer starts to progress, there are several treatment options available that can help people achieve remission. Remission means that people can go through long periods of time without experiencing any symptoms of cancer. While there is no cure for chronic lymphocytic leukemia, there is various current and upcoming treatment. Here’s a look at some of these current and next-gen treatments for chronic lymphocytic leukemia.

What are the Current Treatments for Low-Risk Chronic Lymphocytic Leukemia?

During the early stages of chronic lymphocytic leukemia, there is usually no need for treatment.(1,2) Doctors diagnose and stage this type of cancer with the help of a staging system known as the Rai System.(3,4) Low risk chronic lymphocytic leukemia refers to people who are at stage 0 of the disease under the rai system.(5) In stage 0 of the illness, the spleen, lymph nodes, and liver are not enlarged, and the platelet and red blood cell counts are also normal or near to normal.

If you are at stage 0 and have low-risk chronic lymphocytic leukemia, your oncologist or hematologist is likely to recommend an active surveillance approach, which involves ‘wait and watch’ for symptoms that indicate the cancer is progressing.

A person with low-risk chronic lymphocytic leukemia is unlikely to need further treatment for several years. In fact, many people never need to start treatment, though they will continue to see their doctor for regular follow-ups and laboratory tests to keep an eye on the cancer.

What are the Treatments for High-Risk or Intermediate Chronic Lymphocytic Leukemia?

Intermediate-risk chronic lymphocytic leukemia describes the stages 1 to 2 of chronic lymphocytic leukemia as per the Rai system of staging. People who have stage 1 or stage 2 chronic lymphocytic leukemia have developed enlarged lymph nodes, and they may also have an enlarged liver and spleen. However, they are still close to normal platelet, and red blood cell counts.

High-risk chronic lymphocytic leukemia refers to people who have stage 3 or stage 4 of chronic lymphocytic leukemia. This means that by this stage, a person already has an enlarged liver, spleen, or lymph nodes. It is also common to have low red blood cell and platelet counts.

People with intermediate or high-risk chronic lymphocytic leukemia will be told to begin treatment right away. Here are the various treatments used at this stage.

Immunotherapy and Chemotherapy for Chronic Lymphocytic Leukemia

In the past, the conventional treatment for chronic lymphocytic leukemia used to typically involve a combination of immunotherapy agents being used with chemotherapy. These included:

  • Fludarabine and cyclophosphamide(6,7)
  • Bendamustine (brand name Treanda) with rituximab (which is an antibody immunotherapy) for people older than 65 years(8)
  • Fludarabine and cyclophosphamide in combination with rituximab in people younger than 65 years.

Chemotherapy along with other immunotherapies including ofatumumab (brand name Arzerra), alemtuzumab (brand name Campath), and obinutuzumab (brand name Gazyval). These immunotherapies are likely to be used in case the first round of treatment fails to work.(9,10,11)

Targeted Therapies for Chronic Lymphocytic Leukemia

In the past few years, a lot of new research has improved the understanding of the biology of chronic lymphocytic leukemia, which has led to several more targeted therapies. These medications are known as targeted therapies since they are directed at the particular proteins that help the cancerous cells grow.

Few examples of targeted drugs used for treating chronic lymphocytic leukemia include:

  • duvelisib (brand name Copiktra): targets a kinase protein known as PI3K, but usually used as a last resort when all other treatments have failed.(12,13)
  • ibrutinib (brand name Imbruvica): this drug targets an enzyme known as Bruton’s tyrosine kinase (BTK). This enzyme is critical for the survival of the chronic lymphocytic leukemia cells.(14,15)
  • acalabrutinib (brand name Calquence): this is also a BTK inhibitor that was recently approved in late 2019 for the treatment of chronic lymphocytic leukemia.(16)
  • venetoclax (brand name Venclexta): this drug targets a protein known as BCL2, which is often observed in chronic lymphocytic leukemia.(17,18) It is typically used in combination with the immunotherapy drug obinutuzumab (brand name Gazyva)
  • idelalisib (brand name Zydelig): it blocks the kinase protein PI3K and is typically used in cases of relapsed chronic lymphocytic leukemia.(19)

Other Treatments for Chronic Lymphocytic Leukemia

  • Radiation Therapy: Radiation therapy is a type of cancer treatment that uses high-energy waves or particles to kill the cancerous cells in the body and shrink the enlarged lymph nodes. Radiation therapy is often used in the advanced stages of many types of cancer, but it is not a very popular treatment option in chronic lymphocytic leukemia.(20)
  • Blood transfusions: If your red blood cell counts go down, you might need to receive intravenous blood transfusions to increase the blood cell counts.(21)
  • Bone marrow and stem cell transplants: If your cancer fails to respond to any of these treatments, your doctor may recommend a stem cell transplant. A stem cell transplant will allow you to receive higher doses of chemotherapy for killing more of the cancer cells. However, since higher doses of chemotherapy may cause damage to your bone marrow, you will likely receive additional bone marrow or stem cells from a healthy donor to replace the damaged cells.

Next-Gen Treatments for Chronic Lymphocytic Leukemia

There are several breakthrough treatments currently under investigation for treating chronic lymphocytic leukemia. Some of these have been recently approved by the US Food and Drug Administration (FDA). These include:

  1. CAR T-cell Therapy

    One of the most exciting future treatments for chronic lymphocytic leukemia is CAR T-cell therapy, which stands for Chimeric Antigen Receptor T-cell Therapy. This unique therapy uses cells from the person’s own immune system to fight against cancer. The procedure involves taking out and changing the immune cells so that they are able to better recognize and destroy the cancer cells. The altered immune cells are then put back into the body and allowed to multiply and fight against the cancer.(21,22)

    While CAR T-cell therapies hold a lot of promise, they are not without risks. One of the biggest risks is a condition known as cytokine release syndrome, which is an inflammatory response of the body brought on by the infusion of the modified CAR T-cells. Some people may even experience such severe reactions that it may ultimately result in death if not treated immediately.

  2. Drug Combinations

    The US Food and Drug Administration approved the use of the drug venetoclax (brand name Venclexta) combined with obinutuzumab (brand name Gazyva) in late 2019. This drug combination is used to treat previously untreated chronic lymphocytic leukemia and is a chemotherapy-free option.

    In August 2019, a Phase III clinical trial found that a combination of ibrutinib (brand name Imbruvica) and rituximab can help keep people free of the disease for a more extended period of time as compared to the standard of care in use currently.(23)

    Such types of drug combinations increase the odds of more people being able to make do without needing chemotherapy in the future. Such non-chemotherapy treatments are especially essential for people who are unable to tolerate some of the harsher side effects of chemotherapy.

  3. Other Drugs Being Evaluated For Treating Chronic Lymphocytic Leukemia

    Some of the other targeted therapy drugs that are presently being investigated in clinical trials for treating chronic lymphocytic leukemia include:

    • cirmtuzumab (UC-961)
    • nivolumab (Opdivo)
    • tirabrutinib (ONO-4059 or GS-4059)
    • zanubrutinib (BGB-3111)
    • ublituximab (TG-1101)
    • entospletinib (GS-9973)
    • pembrolizumab (Keytruda)
    • umbralisib (TGR-1202)

    Upon the completion of the clinical trials, we can expect some of these drugs to be approved for the treatment of chronic lymphatic leukemia. If you are interested in joining a clinical trial, and if your present treatment is not working for you, you can always discuss the possibility with your doctor. Clinical trials are used for evaluating the efficiency and safety of new drugs, and they also look at combinations of already approved medications. However, there is no guarantee that these novel treatments will work better than your current treatment. These drugs are, after all, still under trial. There are hundreds of ongoing clinical trials that are focused on the treatment of chronic lymphatic leukemia.


Most people who are diagnosed with chronic lymphatic leukemia do not need to begin their treatment right away. It is only when the disease starts to advance, and you start experiencing the symptoms that your doctor will recommend starting treatment. There are many treatment options available for chronic lymphatic leukemia, and a wide range of next-generation therapies and drugs are under development. You can discuss the possibility of joining a clinical trial with your doctor if your current treatment is not working.


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  12. Vangapandu, H.V., Jain, N. and Gandhi, V., 2017. Duvelisib: a phosphoinositide-3 kinase δ/γ inhibitor for chronic lymphocytic leukemia. Expert opinion on investigational drugs, 26(5), pp.625-632.
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Sheetal DeCaria, M.D.
Sheetal DeCaria, M.D.
Written, Edited or Reviewed By: Sheetal DeCaria, M.D. This article does not provide medical advice. See disclaimer
Last Modified On:August 3, 2022

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