Understanding Targeted Therapies for Chronic Lymphocytic Leukemia (CLL)
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.
Which Therapies Specifically Target 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 are designed to 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 steroidsdexamethasone 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
6 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:
Do you even need treatment?
Most of the time, CLL gets worse slowly. It may be years before it causes problems for you, and when it does, you may be able to manage well by just treating the symptoms.
Doctors usually don’t recommend starting systemic therapy for CLL unless it’s growing quickly or the symptoms and complications have become worse than the possible side effects of treatment. That’s called “watch and wait,” “observation,” or “active surveillance.”
So far, it hasn’t been shown that getting treatment early will help you live longer than waiting, but clinical trials are looking into the best time to start.
What are your goals?
It’s important to decide what you want out of treatment. Are you hoping to have no signs of disease for as long as possible (remission)? Do you want the best quality of life you can get with the least amount of medication side effects? Your doctor can help you understand what results you can expect from the different treatment options.
What’s your unique situation?
You’ll have tests to examine the cancer cells for gene changes that give your doctor an idea of how aggressive the cancer is and which treatments may work best. Your age, your overall health, and any other medical conditions you have also make a difference. If you’ve already had treatment, your doctor will consider how well that worked.
How convenient are the treatments?
Targeted therapies come in different forms and last for different amounts of time. While you can take some medications at home, you have to go to a hospital or clinic for others. Do you live close enough to a treatment center for that to be practical? Are you OK with needles?
Think about whether you’re willing to take pills every day for the rest of your life. Some people would rather have a more intense type of therapy if it means they can be finished with treatment for months or years.
What side effects will you accept?
Targeted therapy is considered an aggressive treatment and can have serious side effects. Some side effects last for a short time then get better. Others may last even after you stop treatment. Talk to your doctor about what might happen so you can decide if the possible benefits outweigh the risks.
How much will you have to pay?
Targeted therapy drugs can cost many thousands of dollars a month. Even if you have health insurance, you might still have significant out-of-pocket costs. And some drugs aren’t covered until you’ve tried one or more other treatments first. Your plan administrator can help you understand what you’ll pay.