Chronic Lymphocytic Leukemia: Your Complete Treatment Guide
Learn how to manage CLL with the latest treatment options and lifestyle strategies.
Published on July 24, 2024
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Chronic lymphocytic leukemia (CLL) is a type of blood cancer that most often affects older adults. It happens when your bone marrow, which is the spongy tissue inside your bones, makes too many lymphocytes, a type of white blood cell.
CLL is a slow-growing cancer that develops over a long period of time. Initially, doctors may not recommend any treatment if the disease is caught early, since CLL is slow-growing, often symptom-free, and its treatments can cause harmful side effects. However, when treatments are needed, they may include targeted therapy, chemotherapy, immunotherapy, stem cell transplant, radiation therapy, surgery, or leukapheresis.
There is no cure for CLL, but these treatments can help you effectively manage the disease and go into remission for a long time. The therapies you receive may depend on how advanced your cancer is, your overall health, your symptoms, and other factors.
Additionally, your doctor will likely recommend testing your cancer for certain genetic changes. The results from these tests might reveal the best treatment options for you.
Be sure to talk to your healthcare provider before starting or combining any type of treatments for CLL.
Watchful Waiting
If CLL isn’t causing symptoms or other problems, your doctor may choose not to treat you right away. Studies suggest that treating patients with early-stage CLL doesn’t improve survival. This way you won’t have to deal with the potential side effects and complications of treatments.
Instead, your doctor will carefully monitor your cancer and recommend treatment only when it progresses. This is often referred to as active surveillance or “watchful waiting.”
Targeted Therapy for Chronic Lymphocytic Leukemia
Targeted therapies work by focusing on specific proteins on cancer cells that help them grow. They can be combined with chemotherapy, immunotherapy, or other treatments. Targeted therapy is usually the first option doctors try when treatment for CLL becomes necessary. These medications are usually taken by mouth.
The following are targeted treatments used for CLL.
Targeted Therapy Drug Class
Drugs Approved for Chronic Lymphocytic Leukemia
BTK Inhibitors
acalabrutinib (Calquence)
ibrutinib (Imbruvica)
zanubrutinib (Brukinsa)
pirtobrutinib (Jaypirca)
BCL2 Inhibitors
venetoclax (Venclexta)
PI3K Inhibitors
duvelisib (Copiktra)
idelalisib (Zydelig)
Bruton’s Tyrosine Kinase (BTK) Inhibitors
These medicines work by blocking the protein BTK, which helps CLL cells grow and multiply. BTK inhibitors that can be used for initial treatment of CLL include:
- acalabrutinib (Calquence)
- ibrutinib (Imbruvica)
- zanubrutinib (Brukinsa)
Pirtobrutinib (Jaypirca) is used to treat CLL after at least two other treatments have been tried with no response.
Side effects of these medicines may include:
- Bleeding
- Chills and fever
- Cough
- Diarrhea
- Headache
- Fatigue
- Heart problems
- Infection
- Liver or kidney problems
- Nausea and vomiting
- Pain
- Skin Rash
- Tumor lysis syndrome (a life-threatening condition that can happen when cancer cells release their contents into the bloodstream)
BCL2 Inhibitors
Venetoclax (Venclexta) is a BCL2 inhibitor. It works by targeting BCL2, a protein that helps CLL cells live longer than they should. Venetoclax is given by mouth as a pill. Side effects include:
- Diarrhea
- Fatigue
- Headache
- Infection
- Low blood cell counts
- Nausea or vomiting
- Pain
- Skin rash
- Tumor lysis syndrome
PI3K Inhibitors
These drugs target phosphatidylinositol 3-kinases (PI3Ks), which are a group of proteins that affect cell growth. These are usually given after other treatments have been tried with limited response. PI3K inhibitors used for CLL include:
- duvelisib (Copiktra)
- idelalisib (Zydelig)
Duvelisib is given as a pill twice a day. It may cause cough, diarrhea, fatigue, fever, infections, joint and muscle pain, low blood cell counts, nausea, pneumonia, stomach pain, skin problems, liver damage, lung inflammation, or serious allergic reactions.
Idelalisib is also given as a pill twice a day. Side effects may include chills, cough, diarrhea, fatigue, fever, low blood cell counts, nausea, skin problems, liver damage, lung inflammation, allergic reactions, reactivation of old infections, or holes in the intestines.
Chemotherapy for Chronic Lymphocytic Leukemia
Chemotherapy uses drugs to kill cancer cells throughout the body. It may be given via an IV or a pill. It’s usually administered in cycles, with time to rest and recover between each treatment period. Chemo medicines are often used together with another chemo drug or combined with other types of treatments.
When it comes to CLL, doctors commonly recommend the following chemotherapy medicines:
Chemotherapy Drug Class
Drugs Approved for Chronic Lymphocytic Leukemia
Antimetabolites
fludarabine (Fludara)
pentostatin (Nipent)
cladribine (2-CdA, Leustatin)
Alkylating Agents
chlorambucil (Leukeran)
bendamustine (Treanda)
cyclophosphamide (Cytoxan)
Antimetabolites are drugs that interfere with DNA production, stopping cancer cell growth. Alkylating agents damage the DNA of cells, preventing them from dividing and causing them to die.
Side effects of chemotherapy may include easy bleeding or bruising, fatigue, frequent infections, hair loss, loss of appetite, mouth sores, nausea, or vomiting.
Immunotherapy for Chronic Lymphocytic Leukemia
Immunotherapy boosts your body’s own immune system to attack cancer. These are the immunotherapy treatments used for CLL.
Immunotherapy Drug Class
Drugs Approved for Chronic Lymphocytic Leukemia
Monoclonal Antibodies
rituximab (Rituxan)
obinutuzumab (Gazyva)
ofatumumab (Arzerra)
alemtuzumab (Campath)
CAR T-Cell Therapy
lisocabtagene maraleucel (Breyanzi)
Monoclonal Antibodies
Monoclonal antibodies are synthetic versions of antibodies that live in your immune system. Generally, monoclonal antibodies work by attaching to proteins on the surface of cancer cells to help your immune system identify and destroy the bad cells. They are administered as an IV and can be given with chemo or a targeted medicine.
Monoclonal antibodies for CLL that focus on a protein called CD20 include rituximab (Rituxan), obinutuzumab (Gazyva), and ofatumumab (Arzerra).
Another monoclonal antibody, alemtuzumab (Campath), targets the CD52 protein. Alemtuzumab is especially helpful for CLL patients with a genetic abnormality called a chromosome 17 deletion.
These immunotherapy drugs can cause mild side effects, such as chills, fever, nausea, rash, fatigue, injection-site reactions, constipation, or headaches. Sometimes, they can trigger more serious symptoms, such as chest pain, a racing heart, swelling of the face and tongue, coughing, trouble breathing, infection, or dizziness. Additionally, these medicines can lead to a reactivation of the hepatitis B infection if you’ve previously had one, stroke, severe infections, progressive multifocal leukoencephalopathy (a rare, serious viral infection that damages the brain), or tumor lysis syndrome.
CAR T-Cell Therapy
With chimeric antigen receptor (CAR) T-cell therapy, a patient’s immune cells, called T cells, are removed from their blood. The T cells are altered in a lab by adding special receptors to their surface. Then the newly engineered T cells are reinfused into the patient. Once in the blood, these new T cells multiply, seek out, and destroy cancer cells.
Lisocabtagene maraleucel (Breyanzi) is the first and only CAR T-cell therapy available for CLL. It received FDA approval on March 14, 2024, for the treatment of CLL that has not responded to at least two previous treatments, including a BTK inhibitor and a BCL2 inhibitor.
CAR T-cell therapy can cause serious side effects, such as allergic reactions during the infusion, serious infections, low blood cell counts, seizures, tremors, trouble speaking and understanding, loss of balance, changes in consciousness, and cytokine release syndrome (a potentially life-threatening condition that happens when your immune system overreacts).
Stem Cell Transplant for Chronic Lymphocytic Leukemia
A stem cell transplant, which is also called a bone marrow transplant, is an option for people with CLL types that are harder to treat, such as those with chromosome 17 deletions or TP53 mutations. It’s not clear yet how helpful stem cell transplants are for people with CLL. When a stem cell transplant for CLL is done, it’s usually done as part of a clinical trial.
With a stem cell transplant, chemotherapy is first used to wipe out the bad stem cells in the bone marrow that are causing CLL. Then healthy stem cells — usually from a donor — are infused into your blood. These new cells help your bone marrow make good blood cells.
This treatment can cause severe or life-threatening side effects, such as serious infections, bleeding, other issues associated with low blood cell counts, and graft-versus-host disease (when immune cells from the donor attack your body).
Radiation Therapy for Chronic Lymphocytic Leukemia
With radiation, high-energy particles or rays destroy cancer cells in the body. Radiation therapy is sometimes used for people with CLL to lessen pain due to an enlarged spleen or swollen lymph nodes.
Common side effects of radiation may include fatigue and irritated skin.
Surgery for Chronic Lymphocytic Leukemia
Surgery isn’t a common treatment for CLL. However, in rare cases doctors may perform a splenectomy, which is a procedure to remove the spleen. With CLL, your spleen can grow large and put pressure on nearby organs, which may lead to pain. A splenectomy can help lessen the symptoms of an enlarged spleen.
Leukapheresis for Chronic Lymphocytic Leukemia
Leukapheresis is a treatment for CLL patients with very high white blood cell levels. When white blood cells levels get very high, blood circulation problems can develop, leading to breathing problems and heart failure.
With this procedure, your blood is passed through a machine that filters out white blood cells and returns the rest of your blood back to your body. Your calcium levels can sometimes drop during this process, which can lead to numbness, tingling, or muscle spasms.
Clinical Trials for Chronic Lymphocytic Leukemia
Clinical trials are research studies that test the safety and effectiveness of different treatments. Many current therapies, such as targeted medicines and immunotherapy, were first studied in clinical trials before they became standard treatment options. Participating in a clinical trial may be a way to receive a novel treatment that isn’t available yet to the public.
There are several treatments and drug combinations on the horizon for CLL that are currently being investigated in these types of studies. If you think you might be interested in joining a clinical trial, ask your doctor for help finding one that may be right for you.
Lifestyle Changes
There’s no known way to prevent CLL, but some lifestyle habits can help you reduce symptoms and better manage your disease.
- Protect yourself from infection. Get up to date on your vaccinations, and wash your hands regularly to prevent infections.
- Reduce stress. Having a cancer diagnosis can be stressful. You may want to try meditation or deep breathing exercises to help lower stress levels.
- Get regular screenings. If you have CLL, you may also have an increased risk of developing other cancers, such as lung cancer, colon cancer, or skin cancer. Don’t skip screenings that could help detect these cancers early.
- Follow a healthy diet. A well-balanced diet that includes lots of vegetables, fruits, and whole grains can improve your overall health.
- Exercise. Physical activity can help cancer patients maintain their health and strength, reduce stress, and boost their mood.
Complementary and Integrative Approaches
Some complementary and integrative approaches can help people with CLL feel better and may lessen treatment side effects, such as fatigue. Popular therapies include acupuncture, massage, and yoga. Be sure to talk to your doctor before adding any type of complementary therapy to your treatment regimen.
Pain Management
If CLL causes pain, there are many therapies to help ease the discomfort. These include:
- Over-the-counter pain relievers like nonsteroidal antiinflammatory drugs (aspirin, ibuprofen [Advil], or naproxen [Aleve]) and acetaminophen (Tylenol) for moderate pain
- Opioids, such as morphine, oxycodone, or hydrocodone, for moderate to severe pain
- Antidepressants and antiepileptics for nerve and neuropathy-related pain
- Steroids for pain caused by swelling or inflammation
It’s important to speak with your doctor about which medicines to take, how to take them, how much to take, and how often you should take them before starting any pain medications. This includes over-the-counter medications you can get without a prescription because some people should not take these medicines, even if they’ve taken them before.
Mental Health Treatment
A cancer diagnosis can take a toll on your mental health. Staying connected with family and friends can help you cope with emotional challenges. Some people also benefit from joining an online or in-person support group where they can interact with other cancer survivors. If symptoms, such as severe sadness or hopelessness, become severe, you may want to speak to a mental health professional who can offer you resources or medication options.
The Takeaway
- CLL is generally a slow-growing cancer. You may not require any treatment when you are first diagnosed.
- As your cancer progresses, chemotherapy, targeted drugs, immunotherapy, stem cell transplant, radiation, surgery, or leukapheresis may be options.
- Your health care team can help you determine the best therapy for you.
Resources We Trust
- Mayo Clinic: Chronic Lymphocytic Leukemia
- Cleveland Clinic: Exploring Novel Strategies for Chronic Lymphocytic Leukemia
- Leukemia & Lymphoma Society: Complications of CLL or CLL Treatment
- American Cancer Society: Supportive or Palliative Care for Chronic Lymphocytic Leukemia
- MD Anderson Cancer Center: 7 Pain Management Options for Cancer Patients You Might Not Know About
Meet Our Experts
Conor Steuer, MD
Medical Reviewer
Conor E. Steuer, MD, is medical oncologist specializing in the care of aerodigestive cancers, mesothelioma, and thymic malignancies and an assistant professor in the department of ...
Julie Lynn Marks
Author
Julie Marks is a freelance writer with more than 20 years of experience covering health, lifestyle, and science topics. In addition to writing for Everyday Health, her work has bee...
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Everyday Health follows strict sourcing guidelines to ensure the accuracy of its content, outlined in our editorial policy. We use only trustworthy sources, including peer-reviewed studies, board-certified medical experts, patients with lived experience, and information from top institutions.
Resources
- Chronic Lymphocytic Leukemia (CLL). Cleveland Clinic. January 31, 2023.
- Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version. National Cancer Institute. January 19, 2024.
- Chronic Lymphocytic Leukemia. Moffitt Cancer Center.
- Treatment. Leukemia & Lymphoma Society.
- Chronic Lymphocytic Leukemia. Mayo Clinic. May 3, 2024.
- Targeted Therapy Drugs for Chronic Lymphocytic Leukemia. American Cancer Society. July 1, 2024.
- Targeted Therapy for Chronic Lymphocytic Leukemia. Canadian Cancer Society. August 2023.
- Chemotherapy for Chronic Lymphocytic Leukemia (CLL). American Cancer Society. July 1, 2024.
- Arnold-Korzeniowsk K. Fludarabine (Fludara). OncoLink. June 19, 2023.
- Bach C. Chlorambucil (Leukeran). OncoLink. July 5, 2023.
- Immunotherapy for Chronic Lymphocytic Leukemia (CLL). American Cancer Society. July 1, 2024.
- FDA Approves First CAR T-Cell Therapy for Chronic Lymphocytic Leukemia. Leukemia & Lymphoma Society. March 19, 2024.
- CAR T-Cell Therapy and Its Side Effects. American Cancer Society. March 1, 2022.
- Cytokine Release Syndrome. National Cancer Institute.
- Stem Cell Transplant for Chronic Lymphocytic Leukemia. American Cancer Society. July 1, 2024.
- Stem Cell or Bone Marrow Transplant Side Effects. American Cancer Society. March 20, 2020.
- Radiation Therapy Side Effects. National Cancer Institute. January 11, 2022.
- Surgery for Chronic Lymphocytic Leukemia (CLL). American Cancer Society. July 1, 2024.
- Supportive or Palliative Care for Chronic Lymphocytic Leukemia. American Cancer Society. July 1, 2024.
- Treatment Clinical Trials for Chronic Lymphocytic Leukemia (CLL). National Cancer Institute.
- Pain Treatment. Leukemia & Lymphoma Society.