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Chronic Lymphocytic Leukemia – Treatment Options

In cancer care, different types of doctors often work together to create a patient’s overall treatment plan that combines different types of treatments. This is called a multidisciplinary team. Cancer care teams include a variety of other health care professionals, such as physician assistants, oncology nurses, social workers, pharmacists, counselors, dietitians, and others.

Treatment options and recommendations depend on several factors, including the type and stage of leukemia, possible side effects, and the patient’s preferences, age, and overall health. Your care plan may also include treatment for symptoms and side effects, an important part of cancer care. Because CLL often develops slowly, many people may not need treatment right away, and some may never need treatment at all. Although the current standard treatments can be highly effective, it is uncertain whether any treatment can completely get rid of CLL, and most patients are not cured of the disease with treatment. The goal of treatment is to ease symptoms and produce a long-term remission (see below).

Descriptions of the common types of treatment used for CLL are listed below. Take time to learn about all of your treatment options and be sure to ask questions about things that are unclear. Talk with your doctor about the goals of each treatment and what you can expect while receiving the treatment.

Watch and wait/active surveillance for early-stage CLL

Patients with symptoms and/or large amounts of CLL in the blood, lymph nodes, or spleen often need treatment shortly after diagnosis. For other patients, however, immediate treatment is not needed. For these people, it is recommended that the disease be monitored carefully without active treatment. This is the standard approach for patients with early-stage disease and no symptoms. This approach might be hard to understand, which can be stressful. However, patients may find that their concerns about this approach lessen over time. Talk with your health care team if you have questions or concerns.

During this time, the patient’s blood counts are watched closely and physical examinations are performed on a regular basis. If the CLL shows signs of worsening, active treatment would then begin. Research studies have shown that no harm comes from the watch-and-wait approach, also called active surveillance or watchful waiting, when compared with immediate treatment for early-stage CLL. Some patients do not develop symptoms for years, or even decades, and will never need any treatment. Patients who have not had their blood counts change over several months or years may only need to have these checked every 3 to 6 months.

Although many patients can live comfortably with CLL without active treatment, it is beneficial to use this time to improve overall health. This includes stopping smoking and bringing all immunizations up to date. However, patients with CLL should not receive the herpes zoster (shingles) vaccine because it may cause a shingles infection in patients who have a lowered immune system.

Treatment is recommended for people with worsening blood counts who have also developed symptoms. These symptoms might include increased fatigue, night sweats, enlarged lymph nodes, or lowered red blood cell or platelet counts. People with CLL are encouraged to talk with their doctor about whether their symptoms need treatment, balancing the benefits of treatment with the risk of side effects

Therapies using medication

Systemic therapy is the use of medication to destroy cancer cells. This type of medication is given through the bloodstream to reach cancer cells throughout the body. Systemic therapies are generally prescribed by a hematologist-oncologist.

Common ways to give systemic therapies include an intravenous (IV) tube placed into a vein using a needle or in a pill or capsule that is swallowed (orally). Systemic therapies may also be given as an injection under the skin, called a subcutaneous injection.

The types of systemic therapies used for CLL include:

Each of these types of therapies are discussed below in more detail. A person may receive only 1 type of systemic therapy at a time or a combination of systemic therapies given at the same time. They can also be given as part of a treatment plan that includes surgery and/or radiation therapy.

The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications prescribed for you, their purpose, and their potential side effects or interactions with other medications.

Chemotherapy

Chemotherapy is the use of drugs to destroy cancer cells, usually by ending the cancer cells’ ability to grow and divide.

Common drugs for CLL include:

The side effects of chemotherapy depend on the individual and the dose used, but they can include fatigue, risk of infection, nausea and vomiting, hair loss, loss of appetite, and diarrhea. These side effects usually go away after treatment is finished.

Targeted therapy

Targeted therapy is a treatment that targets the leukemia’s specific genes, proteins, or the tissue environment that contributes to its growth and survival. This type of treatment blocks the growth and spread of leukemia cells while limiting damage to healthy cells.

Not all cancers have the same targets. To find the most effective treatment, your doctor may run tests to identify the genes, proteins, and other factors in your leukemia. This helps doctors better match each patient with the most effective treatment whenever possible. In addition, research studies continue to find out more about specific molecular targets and new treatments directed at them. Targeted therapy for CLL includes:

Monoclonal antibodies. A monoclonal antibody recognizes and attaches to a specific protein in the surface of leukemia cells, and it does not affect cells that do not have that protein. Monoclonal antibodies for CLL include:

Kinase inhibitors. Kinases are enzymes found in both healthy cells and cancer cells. Some cancer cells can be destroyed by drugs that block a particular kinase enzyme. Kinase inhibitors for CLL are fairly new and may only be available for patients with CLL that has returned (called recurrent CLL) or worsened (called refractory CLL) or in clinical trials.

The side effects of targeted therapy depend on the drug used. Often, a person’s first treatments with rituximab, obinutuzumab, or ofatumumab cause fevers and chills, which usually go away after the first few treatments. Treatment with venetoclax may cause kidney failure and tumor lysis syndrome (TLS), a life-threatening medical emergency that could occur after treatment. However, your doctor may prescribe certain medications to help relieve these symptoms.

Combining systemic therapies

A treatment regimen, or schedule, usually consists of a specific number of cycles given over a set period of time. Sometimes, a doctor may use a combination of drugs, but a combination of drugs is not always better than a single drug. When treatment begins, doctors may use a number of different drugs depending on the stage of the disease and the person’s age and health.

The combinations listed below may be used for CLL. Combinations that include fludarabine are generally used for younger patients:

Bone marrow transplantation/stem cell transplantation

A bone marrow transplant is a medical procedure in which bone marrow that contains leukemia is replaced by highly specialized cells, called hematopoietic stem cells, that develop into healthy bone marrow. Hematopoietic stem cells are blood-forming cells found both in the bloodstream and in the bone marrow. Today, this procedure is more commonly called a stem cell transplant, rather than bone marrow transplant, because it is the stem cells in the blood that are typically being transplanted, not the actual bone marrow tissue.

There are 2 types of stem cell transplantation depending on the source of the replacement blood stem cells: allogeneic (ALLO) and autologous (AUTO). ALLO uses donated stem cells, while AUTO used the patient’s own stem cells. ALLO is the type of transplant used for treating CLL and is typically considered for younger patients either when the standard treatments have not worked well or the patient has a high risk of the CLL returning more quickly. The goal is to destroy all of the cancer cells in the marrow, blood, and other parts of the body using high doses of chemotherapy and/or radiation therapy and then allow replacement blood stem cells to create healthy bone marrow.

Side effects depend on the type of transplant, your general health, and other factors.

Radiation therapy

Radiation therapy is the use of high-energy x-rays or other particles to destroy cancer cells. A doctor who specializes in giving radiation therapy to treat cancer is called a radiation oncologist. A radiation therapy regimen, or schedule, usually consists of a specific number of treatments given over a set period of time. Radiation therapy is not often used to treat CLL because the disease is located throughout the body. However, radiation therapy can be very helpful to shrink an enlarged spleen or swollen lymph nodes and relieve certain symptoms.

Side effects from radiation therapy may include fatigue, mild skin reactions, upset stomach, and loose bowel movements. Most side effects go away soon after treatment is finished.

Surgery

Occasionally, surgery to remove the spleen, called a splenectomy, may be recommended because the spleen can become very enlarged in a person with CLL. A surgical oncologist is a doctor who specializes in treating cancer using surgery.

Before surgery, talk with your health care team about the possible side effects from the specific surgery you will have.

Care for symptoms and side effects

Leukemia and its treatment often cause side effects. In addition to treatments intended to slow, stop, or eliminate the disease, an important part of care is relieving a person’s symptoms and side effects. This approach is called palliative or supportive care, and it includes supporting the patient with his or her physical, emotional, and social needs.

Palliative care is any treatment that focuses on reducing symptoms, improving quality of life, and supporting patients and their families. Any person, regardless of age or type and stage of cancer, may receive palliative care. It works best when palliative care is started as early as needed in the cancer treatment process. People often receive treatment for the leukemia at the same time that they receive treatment to ease side effects. In fact, people who receive both at the same time often have less severe symptoms, better quality of life, and report they are more satisfied with treatment.

Palliative treatments vary widely and often include medication, nutritional changes, relaxation techniques, emotional support, and other therapies. You may also receive palliative treatments similar to those meant to eliminate the CLL, such as chemotherapy or radiation therapy. Talk with your doctor about the goals of each treatment in your treatment plan.

Palliative treatments for CLL may include:

Before treatment begins, talk with your health care team about the possible side effects of the specific treatment plan and palliative care options. During and after treatment, be sure to tell your doctor or another health care team member if you are experiencing a problem so it can be addressed as quickly as possible.

Refractory CLL

If the leukemia does not respond to treatment, the disease is called refractory. If this happens, it is a good idea to talk with doctors who have experience in treating it. Doctors can have different opinions about the best standard treatment plan. Clinical trials might also be an option. Consider getting a second opinion before starting treatment, so you are comfortable with your chosen treatment plan.

If CLL becomes resistant to 1 drug, meaning that the drug no longer works, other treatments or drugs are often recommended. Palliative care will also be important to help relieve symptoms and side effects.

For most people, a diagnosis of refractory CLL is very stressful and, at times, difficult to bear. You and your family are encouraged to talk about how you feel with doctors, nurses, social workers, or other members of the health care team. It may also be helpful to talk with other patients, including through a support group.

Remission

The goal of treatment is to relieve any symptoms from CLL and to reduce the amount of remaining CLL as much as possible. A complete remission (CR) occurs when the doctor cannot find any evidence of leukemia remaining after repeated testing. A partial remission (PR) is when there is some leukemia remaining.

A PR is most common for people with CLL who receive the current standard treatments. With a PR, patients can feel quite well with normal blood counts, have no swollen lymph nodes or spleen, but still have detectable amounts of CLL in the bone marrow.

New monitoring methods, called minimal residual disease (MRD; cancer cells not destroyed by treatment) methods, are better able to find fewer abnormal lymphocytes, as well as tell the difference between the abnormal and healthy lymphocytes. MRD methods are now being used more often to determine depth of remission in patients with CLL.

The goal of newer, more intensive treatments or targeted therapies is to destroy more cancer cells in the hope of lengthening a person’s life. In the future, the definition of a CR in CLL is likely to change with advances in technology. For example, some sensitive tests can find very small levels of the abnormal DNA changes specific to CLL. When these sensitive tests can no longer find any CLL, it is called a molecular remission.

The chance of recurrence

A remission may be temporary or permanent. This uncertainty causes many people to worry that the cancer will come back. Recurrent CLL is CLL that has come back after treatment. While many remissions last for a long time, it is important to talk with your doctor about the possibility of the disease returning. Understanding your risk of recurrence and the treatment options may help you feel more prepared if the leukemia does return.

If there is a recurrence, a new cycle of testing will begin again to learn as much as possible about the recurrence. After this testing is done, you and your doctor will talk about the treatment options. Often the treatment plan will include the treatments described above such as chemotherapy and targeted therapy, but they may be used in a different combination or given at a different pace. Your doctor may suggest clinical trials that are studying new ways to treat this type of recurrent leukemia. Whichever treatment plan you choose, palliative care will be important for relieving symptoms and side effects.

Finding a CLL recurrence does not mean that treatment is needed right away. In fact, the watch-and-wait approach (see above) is usually recommended, with active treatment beginning only if the disease causes symptoms again.

People with recurrent leukemia often experience emotions such as disbelief or fear. You are encouraged to talk with the health care team about these feelings and ask about support services to help you cope.

If treatment does not work

Recovery from leukemia is not always possible. If the cancer cannot be cured or controlled, the disease may be called advanced or terminal.

This diagnosis is stressful, and for many people, advanced cancer may be difficult to discuss. However, it is important to have open and honest conversations with your health care team to express your feelings, preferences, and concerns. The health care team is there to help, and many team members have special skills, experience, and knowledge to support patients and their families. Making sure a person is physically comfortable and free from pain is extremely important.

People who have advanced disease and who are expected to live less than 6 months may want to consider hospice care. Hospice care is designed to provide the best possible quality of life for people who are near the end of life. You and your family are encouraged to talk with the health care team about hospice care options, which include hospice care at home, a special hospice center, or other health care locations. Nursing care and special equipment can make staying at home a workable option for many families.

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