Bendamustine and chlorambucil are the most common chemotherapy drugs used to treat chronic lymphocyte leukemia. They’re usually given with monoclonal antibodies.

Chronic lymphocytic leukemia (CLL) is a slowly progressing type of leukemia. It affects stem cells that will eventually become white blood cells called lymphocytes.

Clinicians often use a wait-and-watch approach for people who receive a diagnosis of CLL — that is, monitoring disease progression before treatment. This is because some forms of CLL may not worsen or require treatment for years. In addition, research has shown that preemptive chemotherapy (chemo) treatment doesn’t improve overall survival rate.

When chemo is used to treat CLL, chemo drugs are typically used in combination with monoclonal antibodies.

This article reviews the chemo drugs that are used to treat CLL, and how they work.

Fludarabine (Fludara) is a type of chemo drug called an antimetabolite. It works by mimicking a building block of DNA. Because cancer cells need to copy their DNA before dividing, the action of fludarabine eventually leads to cell death.

Like many chemo drugs, fludarabine is given intravenously (via an IV). This type of administration allows a drug to enter your bloodstream directly.

According to the American Cancer Society, fludarabine is often one of the first chemo drugs used for CLL. It’s typically given as a part of a combination drug treatment called FCR, which includes:

  • fludarabine
  • cyclophosphamide, another chemo drug
  • rituximab (Rituxan), a monoclonal antibody

A 2021 review notes that FCR has been the standard of care for more than a decade for people with CLL who are younger and in otherwise good health.

Long-term follow-up data from a clinical trial found that people who had FCR continued to have improved survival compared with those who had fludarabine and cyclophosphamide alone. FCR was particularly beneficial in people whose CLL had certain genetic mutations.

Bendamustine (Treanda) is a type of chemo drug called an alkylating agent. These types of chemo drugs work by damaging a cell’s DNA. When DNA becomes too damaged, the cell cannot function properly and dies instead.

Bendamustine is given intravenously. If bendamustine is a part of your CLL treatment plan, it’s typically used in combination with rituximab. This type of cancer treatment is called BR.

Long-term follow-up data from a clinical trial found that, compared with FCR, people over the age of 65 who were in otherwise good health and had received BR had improved outcomes. FCR was still a superior treatment in those younger than 65 years.

Chlorambucil (Leukeran) is an alkylating agent that’s taken by mouth. It may be used for people with CLL who are older and have other conditions that are affecting their overall health.

In the past, chlorambucil was given as a single agent. However, it’s now typically used in combination with monoclonal antibodies like rituximab or obinutuzumab (Gazyva).

An older clinical trial found that chlorambucil with either of these two drugs is superior to chlorambucil alone in older people with CLL who were in poorer health.

However, a 2021 review notes that treatments focusing more on monoclonal antibodies and targeted therapy drugs have largely replaced chlorambucil in this group.

Targeted therapy drugs used to treat CLL

Targeted therapy drugs may also be used as part of the standard care for CLL. These drugs target specific proteins on or in CLL cells, inhibiting their ability to survive.

Targeted therapy drugs for CLL include:

  • Tyrosine kinase inhibitors: These drugs, such as ibrutinib and acalabrutinib, block proteins that cause cancer cell growth, leading to cancer cell death.
  • PI3K inhibitors: By blocking the PI3k proteins, these drugs, such as idelalisib and duvelisib, interrupt signals that allow cancer cells to survive and proliferate.
  • BCL-2 inhibitors: Inhibitors like venetoclax block BCL-2 proteins, helping to lower the survival time of cancer cells.
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In addition to the chemo drugs that we’ve discussed above, there are a couple others that may also be used in the treatment of CLL. Let’s look at these now.


Pentostatin (Nipent) is an antimetabolite chemo drug that’s given intravenously. When pentostatin is used for CLL, it’s used in a combination called PCR, which includes pentostatin, cyclophosphamide, and rituximab.


Cyclophosphamide is an alkylating agent. As mentioned earlier, it’s included along with other chemo drugs and rituximab in the FCR and PCR treatment regimens.

Chemotherapy side effects

Chemo drugs target cells that are growing and dividing quickly. While this largely includes cancer cells, other healthy and rapidly dividing cells in the body can be affected as well.

As such, chemo has a variety of potential side effects. These can vary based on the specific chemo drug. However, some of the most common side effects of chemo are:

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Chemo is given in cycles. A cycle is a period of treatment followed by a period with no treatment that gives your body time to recover from the chemo. A single cycle of chemo typically lasts 3 to 4 weeks.

The exact number of cycles depends on factors like the type of drugs used, the characteristics of your CLL, and your age and overall health. Generally speaking, four to eight cycles are used, meaning you receive chemo for several months.

Questions to ask your doctor

If your doctor recommends chemo for your CLL, it’s important to get all of the facts. Some examples of questions to ask include:

  • What chemo drugs are being recommended?
  • Will my chemo be given in combination with other drugs? If so, which ones?
  • Why have you recommended this type of treatment as opposed to others?
  • How many cycles of chemo are planned? How long is a cycle?
  • Where will I go to receive my chemo and how long will it take?
  • What types of side effects can I expect?
  • What steps can I take to prepare for and manage side effects when they occur?
  • Are there any long-term side effects associated with this chemo?
  • What are the next steps if chemo isn’t effective?
  • Are there any alternatives to chemo? If so, how will they affect my outlook?
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Chemotherapy is one of the treatment types you may receive if you have a diagnosis of CLL. It’s often given in combination with monoclonal antibodies like rituximab.

Two of the common combination drug treatments for CLL that include chemo are FCR and BR. It’s also possible that other drug combinations may be used, depending on your individual situation.

Like all cancer treatments, chemo comes with a variety of side effects. Your care team can help to give you a better idea of what types of side effects to expect with your chemo and the steps that you can take to help manage them.