Chronic lymphocytic leukemia (CLL) is a slow-growing blood cancer that doesn’t always need to be treated. But when it does, targeted therapies are the kinds of drugs doctors recommend most. 

They’re a type of systemic treatment, which means the medicines go throughout your body. But they’re made to work directly on the cancer cells — defective versions of blood cells called B lymphocytes, or B cells, which are a part of your immune system.

Targeted therapies can’t cure CLL, but they can keep it from getting worse or keep you symptom-free for months or even years.

What Are Therapies for Chronic Lymphocytic Leukemia (CLL)?

Several different types of drugs are used in targeted therapy. Some are pills you take every day, while others are liquid infusions you get through a vein. Some you take for a set amount of time, and others you take until they stop working for you.

Many things go into choosing a type of targeted therapy, including:

  • Characteristics of the cancer cells, like gene mutations (changes)
  • Your age, overall health, and other medical conditions
  • Your treatment history

There isn’t one particular drug or drug combination that’s been proven to work best in all cases. You should learn as much as you can about the options so you can work with your doctor to come up with a treatment plan that’s best for you. 

These are the main kinds of targeted therapy for CLL: 

At best, these drugs can bring CLL into remission. That means your blood test results are in the normal range and you don’t have symptoms. You may enjoy remission for many years, but CLL usually comes back and gets worse.

Even if one type of treatment is successful at first, it may eventually stop working. You may  have many different rounds of treatment over your lifetime, with more than one of these types of targeted therapies.

What Are Bruton Tyrosine Kinase (BTK) Inhibitors?

A Bruton tyrosine kinase (BTK) inhibitor will likely be the first type of drug your doctor recommends to treat CLL, but these can be used at any point during treatment. They’re sometimes combined with other types of drugs.

BTK is a protein that immune cells, including B cells, need to grow. It helps send signals that control how they develop, multiply, and stay alive. In CLL, these signals are always on, causing cells to grow out of control. BTK inhibitors attach to these proteins and disable them, blocking the signals. 

If you have serious side effects while you’re taking a BTK inhibitor, your doctor can switch you to a different one, or you can try a different type of treatment.

Learn more about Bruton tyrosine kinase (BTK) inhibitors for CLL.

What Are Monoclonal Antibodies and B-Cell Lymphoma 2 (BCL-2) Inhibitors?

This type of treatment causes the death of cancer cells, either working with your immune system or acting on cancer cells directly. There are two main types of drugs in this category.

Monoclonal antibodies

These drugs are lab-made proteins that seek out and attach to certain targets on the surface of cancer cells. With CLL, the targets are the CD20 and CD52 antigens.

When these drugs attach to their targets, they mark the cells as dangerous, which attracts other parts of your immune system to attack and kill them.

Most monoclonal antibodies are given by intravenous (IV) infusion. You’ll go to a hospital or clinic where the drug is delivered through a needle placed in a vein in your arm. Depending on the drug, you’ll get an infusion once a month or several times a week. Treatment usually continues for about six months.

These drugs are most often used in combination with a different type of targeted therapy. They can also be combined with chemotherapy medications. You can get one as part of your first treatment or after an earlier treatment stops working.

BCL-2 inhibitors

This type of drug kills B cells by working with your body’s natural process for getting rid of old or damaged cells. Normally these cells get a signal to self-destruct. But a protein called BCL-2, which CLL cells have a lot of, blocks this signal and keeps cells from dying. BCL-2 inhibitors attach to this protein and deactivate it.

Venetoclax is the only approved drug in this class. It may be part of your first treatment or a treatment you get after you’ve tried other things. It’s usually combined with a monoclonal antibody, but it can also be used alone. 

Venetoclax comes in pill form, which you’ll take once a day. It’s most often prescribed for a set amount of time, but some people may keep taking it until it stops working.

Learn more about monoclonal antibodies and B-cell lymphoma 2 (BCL-2) inhibitors.

What Are High-dose Steroids?

These drugs put the brakes on many parts of your immune system, including cancerous B cells. The main types of these drugs used in CLL are the steroids dexamethasone and methylprednisone, in much higher doses than you’d get if you were taking them for a different condition. 

High-dose corticosteroids are usually given in combination with a monoclonal antibody drug. They can be used for CLL that is hard to treat. They can also quickly lower the amount of cancer cells in your blood to get you healthy enough for a different type of treatment.

 

Learn more about high-dose steroids .

What Are PI3K Inhibitors?

If other types of treatments have stopped working for you, your doctor might try a targeted drug called a phosphatidylinositol 3-kinase (PI3K) inhibitor. PI3K proteins help send signals that control many different cell processes. Blocking these proteins both stops cells from multiplying and encourages them to die. 

One PI3K inhibitor, idelalisib, is used in combination with the targeted B-cell killer rituximab. Another, duvelisib, can be taken alone. These are pills you take twice a day for as long as they keep working for you or until you can’t manage the side effects.

Learn more about PI3K inhibitors .

Reasons You Might Consider a Clinical Trial for CLL infographic

Things to Consider When Choosing a Treatment

Your doctor will be your best source of advice on whether a targeted therapy is right for you and which one would be most helpful. But your preferences also matter. Here are six things to consider:

Learn More About
● Bruton tyrosine kinase (BTK) inhibitors
● Monoclonal antibodies and B-cell lymphoma 2 (BCL-2) inhibitors
● High-dose steroids
● Phosphatidylinositol 3-Kinase (PI3K) inhibitors

Show Sources

SOURCES:

American Cancer Society: “Typical Treatment of Chronic Lymphocytic Leukemia,” “How Targeted Therapies Are Used to Treat Cancer,” “Targeted Therapy Drugs for Chronic Lymphocytic Leukemia,” “Immunotherapy for Chronic Lymphocytic Leukemia (CLL).”

UpToDate: “Patient education: Chronic lymphocytic leukemia (CLL) in adults (Beyond the Basics).”

National Cancer Institute: “Targeted Therapy to Treat Cancer,” “Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version,” “Chronic Lymphocytic Leukemia Treatment (PDQ®)–Health Professional Version,” “Bcl-2 inhibitor BCL201.”

National Comprehensive Cancer Network: “NCCN Guidelines for Patients: Chronic Lymphocytic Leukemia.”

Cancers: “The Immunomodulatory Mechanisms of BTK Inhibition in CLL and Beyond.”

StatPearls: “Chronic Lymphocytic Leukemia.”

Cancer: “Chronic lymphocytic leukemia (CLL) treatment: So many choices, such great options.”

Leukemia & Lymphoma Society: “Relapsed and Refractory.”

Blood Advances: “BTK inhibitors in CLL: second-generation drugs and beyond.”

Frontiers in Immunology: “BTK Inhibitors in Chronic Lymphocytic Leukemia: Biological Activity and Immune Effects,” “Immunomodulation—a general review of the current state-of-the-art and new therapeutic strategies for targeting the immune system.”

CLL Society: “Steroids in Chronic Lymphocytic Leukemia (Part 1).”

Advances in Medical Science: “Efficacy of high-dose corticosteroid-based treatment for chronic lymphocytic leukemia patients with p53 abnormalities in the era of B-cell receptor inhibitors.”

Archives of Medical Science: “Five years of experience with rituximab plus high-dose dexamethasone for relapsed/refractory chronic lymphocytic leukemia.”

Cancer Medicine: “Chronic lymphocytic leukaemia/small lymphocytic lymphoma treatment with rituximab and high-dose methylprednisolone, revisited.”

Cancer Control: “A Long Way to Go: A Scenario for Clinical Trials of PI3K Inhibitors in Treating Cancer.”

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