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Chronic Lymphocytic Leukemia Treatment Options

Posted on June 29, 2021
Medically reviewed by
Mark Levin, M.D.
Article written by
Maureen McNulty

There are many different treatment options for chronic lymphocytic leukemia (CLL), a blood cancer that starts in the bone marrow. For older people or those with serious medical problems, the general treatment goal is to extend a person’s life and improve their quality of life. A curative approach, which aims to achieve complete remission, may be right for younger healthy people. Many people with this type of leukemia can live for a long time. CLL is a slow-growing cancer and often does not need to be treated right away.

The treatment plan that is best for you depends on factors such as:

  • Your age
  • Your CLL stage
  • What subtype of CLL you have
  • Potential side effects of treatment
  • Your overall health
  • Personal preferences

The goals of chronic lymphocytic leukemia treatment are generally to relieve symptoms, slow the growth of leukemia cells, and help you go into remission. Remission occurs when signs of CLL are reduced or eliminated. For younger and healthier people, a doctor may consider a curative approach. This strategy requires very aggressive treatments, which may be difficult to tolerate for older people or those with chronic medical problems.

Treatments for CLL

Many people who have CLL eventually need treatment. Often, treatment includes some form of systemic therapy. Systemic therapies are medications that can attack cancer cells in all areas of the body. They include chemotherapy and targeted therapy drugs. Other treatments may consist of immunotherapy, a stem cell transplant, or — less commonly — local therapies, radiation, or surgery.

Watch and Wait

Chronic leukemias can grow slowly, so some people with these conditions don’t need treatment right away. Taking a watch-and-wait approach allows people to avoid the side effects that often come with cancer treatments.

While watching and waiting, you will need to have regular doctor’s visits. Your doctor will monitor CLL signs and symptoms so that they know if and when your condition is becoming worse. At your follow-up visits, your doctor may:

  • Ask you about your symptoms
  • Check your lymph nodes to see if any are growing bigger
  • Perform blood tests to see whether your blood cell counts are changing
  • Perform an abdominal exam to check whether your spleen is growing larger
  • Recommend tests to check for damage in your bones or other organs

If you develop new symptoms, or if your CLL signs worsen, your doctor may recommend that you begin treatment.

Chemotherapy

Chemotherapy drugs kill cancer cells by stopping them from growing. Chemotherapies used to treat CLL include:

You may also receive corticosteroids, alone or with chemotherapy. Your doctor may recommend taking Decadron (dexamethasone), Deltasone (prednisone), or Medrol (methylprednisolone). Steroids can help treat cancer, lower inflammation levels, and relieve side effects caused by chemotherapy.

Targeted Therapy

CLL cells often contain gene and protein changes that are not found in normal cells. Targeted therapies can attack any cells that contain these specific changes. People with CLL often receive targeted therapy medications as part of their treatment plan.

Some targeted therapies are inhibitors. They each block a specific protein that cancer cells need in order to grow. Targeted therapies used to treat CLL include:

  • Bruton’s tyrosine kinase inhibitors, including Brukinsa (zanubrutinib), Calquence (acalabrutinib), and Imbruvica (ibrutinib)
  • Phosphoinositide 3-kinase inhibitors, including Copiktra (duvelisib) and Zydelig (idelalisib)
  • The B-cell lymphoma 2 inhibitor Venclexta (venetoclax)

Monoclonal antibodies are another type of targeted therapy. Monoclonal antibodies latch onto proteins found on the surface of cancer cells and stop them from working correctly. Monoclonal antibodies that are used to treat CLL include:

Combining Cancer Treatments

Often, your doctor will recommend that you use a combination of targeted therapy and chemotherapy drugs. Some common combinations for treating CLL include:

  • FCR, comprising fludarabine, cyclophosphamide, and rituximab
  • PCR, which includes pentostatin, cyclophosphamide, and rituximab
  • BR, a pairing of bendamustine and rituximab
  • Obinutuzumab and chlorambucil, often used for older adults

Immunotherapy

Immunotherapy medications help the immune system attack cancer cells. Some people with CLL take the immunotherapy drug Revlimid (lenalidomide). This medication helps activate the body’s T cells to kill leukemia cells.

Additionally, some cases of CLL can be treated with chimeric antigen receptor T-cell (CAR-T) therapy. During CAR-T therapy, a person’s T cells are removed and CAR proteins are added to the T cells’ surfaces. CAR proteins allow the T cell to attach to cancer cells. When the T cells are added back into the body, they can better kill the leukemia cells.

Stem Cell Transplant

Cases of CLL that don’t respond well to chemotherapy and targeted therapy drugs may be treated with allogeneic stem cell transplantation — also called a bone marrow transplant. People who choose this treatment option are first given high doses of chemotherapy. This kills many of the leukemia cells, but it also destroys normal blood cells. Then, during a stem cell transplant, a person with CLL receives healthy blood stem cells from a donor. The blood stem cells can then create new, healthy blood cells.

Radiation Therapy

Radiation therapy uses high-energy beams such as X-rays to kill cancer cells. Radiation therapy is sometimes used to treat CLL symptoms, such as enlarged lymph nodes.

Surgery

Surgery is not a common treatment option for people with CLL. However, some people with CLL develop an enlarged spleen. A splenectomy (surgery to remove the spleen) is sometimes needed in these cases.

Clinical Trials

Some people with CLL may be able to join clinical trials. These studies help test new treatments or new combinations of therapies. Clinical trials help researchers learn whether new treatments are safe and effective. If you participate in a trial, you may be able to access new medications that you wouldn’t otherwise be able to. If you are interested in learning more, talk to your doctor about how to participate.

CLL Subtypes and Treatment Options

There are a few different subtypes of CLL. Each subtype may be treated with slightly different therapies.

B-Cell CLL

Hairy cell leukemia (HCL) is related to CLL. The conditions are similar in that they develop from B cells — white blood cells that fight infection. HCL can often be treated with a watch-and-wait approach. When HCL causes signs and symptoms, doctors often recommend the chemotherapy drugs cladribine or pentostatin. If these drugs do not work or if a person’s HCL returns, rituximab may be an option. Some people with HCL may also receive the immunotherapy drug Intron A (interferon alpha-2b).

People with certain subtypes of B-cell CLL may also be able to use other monoclonal antibodies. Lumoxiti (moxetumomab pasudotox-tdfk) is approved by the FDA to treat HCL. This medication — which blocks a protein called CD22 — may also be helpful for treating B-cell prolymphocytic leukemia (PLL). People with PLL may also be treated with a monoclonal antibody called Campath (alemtuzumab) that targets the protein CD52.

T-Cell CLL

Rarely, CLL may develop from T cells, a different type of white blood cell in the immune system. Doctors may recommend additional treatments for some subtypes of T-cell CLL. Large granular lymphocytic leukemia may be treated with growth factors such as Zarxio (filgrastim). Adult T-cell leukemia/lymphoma treatments may include antiviral drugs like Retrovir (zidovudine).

Deciding on a Treatment Plan

How do you know which treatment is a good fit for you? If you have higher-risk CLL, more aggressive treatments might be a good idea. Doctors measure CLL risk using a system called the CLL International Prognostic Index (CLL-IPI). This system takes into account prognostic factors that increase or decrease your chances of having a worse outlook. The prognostic factors include:

  • Mutations or deletions in the TP53 gene
  • No mutations in the IGHV gene
  • Higher CLL stage
  • Older age
  • The presence of deletion 17p

These factors represent characteristics that are linked with having a poor prognosis (outlook). A person’s CLL-IPI score is based on these prognostic factors. Each factor gets a certain number of points, and the points are added up into a single score. Your score tells you which risk group you are in. Experts have assigned treatment recommendations to each risk group:

  • Low risk — No treatment is necessary.
  • Intermediate risk — No treatment is needed unless the person has severe symptoms.
  • High risk — Treatment is needed unless the person doesn’t have symptoms.
  • Very high risk — Standard treatments may not be effective, and the person should try new therapies or enroll in a clinical trial.

Your doctor may use CLL-IPI when recommending a treatment plan and estimating your outlook.

Shared Decision-Making

Your health care team can make recommendations about treatments, but the decision is ultimately up to you. The process of discussing options with your doctor and deciding as a team is known as “shared decision-making.” A shared decision-making approach can increase your satisfaction with your treatment and make you more likely to stick with it.

To engage in shared decision-making, ask your doctor questions about what to expect with different potential therapies. Ask questions about the benefits of particular drugs — as well as what side effects you may experience. Talk to your doctor about your goals and what you want your life to look like while living with cancer. If you’d like a different perspective, you can seek a second opinion from a different doctor.

Talk With Others Who Understand

MyLeukemiaTeam is a social network for people living with leukemia and their loved ones. On MyLeukemiaTeam, people come together to ask questions, give advice, and share their stories with other people who understand life with leukemia.

Have you been diagnosed with chronic lymphocytic leukemia? Deciding on the right leukemia treatment can be confusing. Ask for others’ experiences with different treatment options in the comments below, or join in the conversation at MyLeukemiaTeam.

All updates must be accompanied by text or a picture.
Mark Levin, M.D. is a hematology and oncology specialist with over 37 years of experience in internal medicine. Review provided by VeriMed Healthcare Network. Learn more about him here.
Maureen McNulty studied molecular genetics and English at Ohio State University. Learn more about her here.

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