Chronic lymphocytic leukemia (CLL) is a slow-growing cancer of the immune system. Because it’s slow-growing, many people with CLL won’t need to start treatment for many years after their diagnosis.

Once the cancer begins to grow, there are many treatment options available that can help people achieve remission. This means people can experience long periods of time when there’s no sign of cancer in their body.

The exact treatment option that you’ll receive depends on a variety of factors. This includes whether or not your CLL is symptomatic, the stage of the CLL based on results of blood tests and a physical exam, and your age and overall health.

While there’s no cure for CLL yet, breakthroughs in the field are on the horizon.

Doctors typically stage CLL using a system called the Rai system. Low-risk CLL describes people who fall in “stage 0” under the Rai system.

In stage 0, the lymph nodes, spleen, and liver aren’t enlarged. Red blood cell and platelet counts are also near normal.

If you have low-risk CLL, your doctor (usually a hematologist or oncologist) will likely advise you to “wait and watch” for symptoms. This approach is also called active surveillance.

Someone with low-risk CLL may not need further treatment for many years. Some people will never need treatment. You’ll still need to see a doctor for regular check-ups and lab tests.

Intermediate-risk CLL describes people with stage 1 to stage 2 CLL, according to the Rai system. People with stage 1 or 2 CLL have enlarged lymph nodes and potentially an enlarged spleen and liver, but close to normal red blood cell and platelet counts.

High-risk CLL describes patients with stage 3 or stage 4 cancer. This means you may have an enlarged spleen, liver, or lymph nodes. Low red blood cell counts are also common. In the highest stage, platelet counts will be low as well.

If you have intermediate- or high-risk CLL, your doctor will likely recommend that you start treatment right away.

Chemotherapy and immunotherapy

In the past, the standard treatment for CLL included a combination of chemotherapy and immunotherapy agents, such as:

  • fludarabine and cyclophosphamide (FC)
  • FC plus an antibody immunotherapy known as rituximab (Rituxan) for people younger than 65
  • bendamustine (Treanda) plus rituximab for people older than 65
  • chemotherapy in combination with other immunotherapies, such as alemtuzumab (Campath), obinutuzumab (Gazyva), and ofatumumab (Arzerra). These options may be used if the first round of treatment doesn’t work.

Targeted therapies

Over the last few years, a better understanding of the biology of CLL has led to a number of more targeted therapies. These drugs are called targeted therapies because they’re directed at specific proteins that help CLL cells grow.

Examples of targeted drugs for CLL include:

  • ibrutinib (Imbruvica): targets the enzyme known as Bruton’s tyrosine kinase, or BTK, which is crucial for CLL cell survival
  • venetoclax (Venclexta): targets the BCL2 protein, a protein seen in CLL
  • idelalisib (Zydelig): blocks the kinase protein known as PI3K and is used for relapsed CLL
  • duvelisib (Copiktra): also targets PI3K, but is typically used only after other treatments fail
  • acalabrutinib (Calquence): another BTK inhibitor approved in late 2019 for CLL
  • venetoclax (Venclexta) in combination with obinutuzumab (Gazyva)

Blood transfusions

You may need to receive intravenous (IV) blood transfusions to increase blood cell counts.


Radiation therapy uses high-energy particles or waves to help kill cancer cells and shrink painful enlarged lymph nodes. Radiation therapy is rarely used in CLL treatment.

Stem cell and bone marrow transplants

Your doctor may recommend a stem cell transplant if your cancer doesn’t respond to other treatments. A stem cell transplant allows you to receive higher doses of chemotherapy to kill more cancer cells.

Higher doses of chemotherapy can cause damage to your bone marrow. To replace these cells, you’ll need to receive additional stem cells or bone marrow from a healthy donor.

A large number of approaches are under investigation to treat people with CLL. Some have been recently approved by the Food and Drug Administration (FDA).

Drug combinations

In May 2019, the FDA approved venetoclax (Venclexta) in combination with obinutuzumab (Gazyva) to treat people with previously untreated CLL as a chemotherapy-free option.

In August 2019, researchers published results from a Phase III clinical trial showing that a combination of rituximab and ibrutinib (Imbruvica) keeps people free of disease for longer than the current standard of care.

These combinations make it more likely people may be able to do without chemotherapy altogether in the future. Non-chemotherapy treatment regimens are essential for those who can’t tolerate harsh chemotherapy-related side effects.

CAR T-cell therapy

One of the most promising future treatment options for CLL is CAR T-cell therapy. CAR T, which stands for chimeric antigen receptor T-cell therapy, uses a person’s own immune system cells to fight cancer.

The procedure involves extracting and altering a person’s immune cells to better recognize and destroy cancer cells. The cells are then put back into the body to multiply and fight off the cancer.

CAR T-cell therapies are promising, but they do carry risks. One risk is a condition called cytokine release syndrome. This is an inflammatory response caused by the infused CAR T-cells. Some people can experience severe reactions that may lead to death if not quickly treated.

Other drugs under investigation

Some other targeted drugs currently being evaluated in clinical trials for CLL include:

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

Once clinical trials are completed, some of these drugs can be approved for treating CLL. Talk to your doctor about joining a clinical trial, especially if current treatment options aren’t working for you.

Clinical trials evaluate the efficacy of new drugs as well as combinations of already approved drugs. These new treatments may work better for you than the ones currently available. There are currently hundreds of clinical trials ongoing for CLL.

Many people who are diagnosed with CLL won’t actually need to start treatment right away. Once the disease starts to progress, you have many treatment options available. There’s also a wide range of clinical trials to choose from that are investigating new treatments and combination therapies.