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If you’re diagnosed with chronic lymphocytic leukemia (CLL), your first thought may be that you’ll have to have chemotherapy. This treatment is very effective for CLL since chemotherapy works quickly to attack cancer cells. But it also kills some healthy cells. That can lead to harsh side effects like hair loss, mouth sores, loss of appetite, nausea, and vomiting, and, perhaps most importantly, low blood cell counts, which raise the risk of infection.

Treatment for CLL goes far beyond chemotherapy. Newer medicines, like targeted therapy and monoclonal antibodies, have revolutionized treatment. These drugs zero in on CLL cells rather than wipe out many cells both bad and good. Since they don’t attack healthy cells, they appear to have fewer unpleasant side effects. As a result, these non-chemo drugs are often the ones doctors try first for CLL.

Here’s a look at treatments for CLL beyond chemotherapy.

Watchful Waiting

If you have early-stage CLL, without symptoms, you may be surprised to learn that many doctors now recommend that you not start treatment right away. Instead, they’ll monitor you closely. You’ll see your doctor for a physical exam about every 3 months and get regular blood tests.

After about a year, your doctor will have a better sense of how aggressive your CLL is and whether or not you need to start treatment. Research shows that people who take this approach do just as well as patients who get chemotherapy right away.

Targeted Therapy

This is often the first-line treatment -- that is, the first approach your doctor will try -- for advanced or symptomatic CLL. People who relapse might get targeted therapy, too. These medicines attack specific traits on cancer cells or processes that help the cells grow, multiply, or survive. You take them as pills once or twice a day.

Targeted drugs for CLL include:

  • Acalabrutinib(Calquence),ibrutinib (Imbruvica), and zanubrutinib (Brukinsa). These drugs, known as tyrosine kinase inhibitors (TKIs), block a substance called tyrosine kinase that causes your stem cells to make too many white blood cells.
  • Venetoclax (Venclexta). This is a drug called a BCL2 inhibitor. It blocks a protein called BCL2 found on cancer cells. This kills them off and makes them more likely to respond to other cancer treatments.
  • Duvelisib (Copiktra) and idelalisib (Zydelig). These two drugs block proteins that help cancer grow, such as P13K-delta. Doctors turn to these drugs after they have tried other CLL treatments.

These drugs may cause mild side effects such as:

  • Diarrhea
  • Nausea
  • Constipation
  • Headache
  • Fatigue
  • Shortness of breath
  • Coughing
  • Swelling of your feet and hands
  • Body aches
  • Muscle and joint pain
  • Rash
  • Anemia and certain infections, due to low blood cell counts

It’s rare, but targeted therapy for CLL can cause more serious side effects such as bleeding, severe infections, irregular heartbeat, liver damage, and lung inflammation. Idelalisib may reactivate old infections such as hepatitis.

Venetoclax can lead to tumor lysis syndrome (TLS). That’s when dead CLL cells break open and dump their contents into your bloodstream. This can cause toxins to build up in your blood, which causes problems with your kidneys, heart, and nervous system. To avoid this, your doctor may start you at a low dose and gradually increase it over a period of weeks.

Monoclonal Antibodies

These treatments attack a type of white blood cell called B lymphocytes that are abnormal in people with CLL and help cancer cells grow. As a result, cancer cells eventually die off. You get this medicine through an IV at a doctor’s office or infusion center. You might get this treatment alone or along with chemotherapy. Several kinds of monoclonal antibodies are available to treat CLL. Different ones target different cancer-promoting proteins.

They include:

Obinutuzumab (Gazyva), ofatumumab (Arzerra), andrituximab (Rituxan). These three drugs target a protein on the surface of B lymphocytes called CD20. During your infusion, you may notice mild side effects like itching, chills, fever, nausea, rashes, fatigue, and headache.

Your doctor will also give you drugs to help prevent more serious side effects like:

  • Chest pain
  • Heart racing
  • Facial and tongue swelling
  • Coughing
  • Trouble breathing
  • Dizziness and fainting

Like targeted therapy, these drugs can also reactivate past hepatitis B infections and raise the risk for other serious infections, such as a rare brain disease known as progressive multifocal leukoencephalopathy (PML).

Alemtuzumab (Campath). This targets CD52, a protein found on the surface of CLL cells. You might get this drug if you haven’t responded to past treatments or if you have a specific form of CLL that includes what’s called a “chromosome-17 deletion.” This medication has side effects like those of other monoclonal antibodies, as well as low red blood cell and platelet counts. Very rarely, it’s been linked to strokes.

Radiation for CLL Symptoms

It’s not the main treatment for CLL, but you might get radiation to help treat some of the cancer’s symptoms. Radiation can:

  • Shrink swollen organs, such as your spleen, that press on other organs and cause pain
  • Ease pain from bone damage due to leukemia cells that grow in the bone marrow

Radiation may cause side effects such as:

  • Skin redness
  • Fatigue
  • Low blood cell counts
  • GI upset, such as nausea, vomiting, and diarrhea


Surgery in Some CLL Cases

It’s rare for doctors to recommend surgery for CLL. The disease spreads through your bone marrow, so surgery can’t cure it. But sometimes, CLL enlarges your spleen so much that it presses on your other organs. An enlarged spleen also lowers your red blood cell and platelet counts. Your doctor may first recommend that you get radiation to shrink your spleen. If that doesn’t work, you may need to have it removed. This works, but it can make you more likely to get infections.

The Best CLL Treatment for You

There’s no single best treatment for CLL. These treatments haven’t been compared to one another in studies, so there’s no way to know if one is better than the others. Your doctor will decide what to give you based on your:

  • Test results
  • Age
  • Overall health
  • Other medical problems
  • Cancer stage
  • Individual genetics
  • Concerns about side effects

While some people with CLL go into complete remission -- which means they have normal blood counts and no symptoms of cancer -- most eventually relapse. In that case, you may get several treatments over the course of your life with CLL.

Show Sources

Photo Credit: SDI Productions / Getty Images


American Cancer Society: “Chemotherapy for Chronic Lymphocytic Leukemia,” “Targeted Therapy Drugs for Chronic Lymphocytic Leukemia,” “Monoclonal Antibodies for Chronic Lymphocytic Leukemia,” “Radiation Therapy for Chronic Lymphocytic Leukemia,” “Surgery for Chronic Lymphocytic Leukemia.”

UpToDate “Chronic Lymphocytic Leukemia (CLL) in Adults (Beyond the Basics),” “Overview of the Treatment of Chronic Lymphocytic Leukemia.”

National Cancer Institute: “Chronic Lymphocytic Leukemia Treatment.”