Chronic lymphocytic leukemia (CLL) treatment often starts with chemotherapy, a monoclonal antibody, or a targeted drug. The goal of these treatments is to put you into remission, meaning you no longer have any signs of cancer in your body.

Sometimes the first drug you try doesn’t work, or your cancer comes back after the treatment. If that happens, your doctor can try new drugs or combinations of drugs. This is called second-line treatment. It may work better than the first therapy you tried.

Your doctor will help you choose your next round of treatment based on:

  • your age
  • your health
  • the stage of your cancer
  • whether you have a gene mutation or missing chromosome
  • which treatment you had before and how well it worked

You may get some of the same drugs again if they worked well for you the first time. Here’s a look at your second-line treatment options for CLL.

Chemotherapy

This treatment uses strong drugs to kill cancer cells all over your body. You’ll get chemotherapy in cycles, meaning that you’ll take the drugs for a few days and then stop for a few days to give your body time to recover. Each cycle lasts three to four weeks.

A few different chemotherapy drugs treat CLL, including:

  • bendamustine (Treanda)
  • chlorambucil (Leukeran)
  • cladribine (Leustatin)
  • cyclophosphamide (Cytoxan)
  • fludarabine (Fludara)
  • lenalidomide (Revlimid)
  • pentostatin (Nipent)

Chemotherapy kills quickly dividing cells. Cancer cells divide quickly, but so do hair cells, blood cells, and immune cells. Damage to these healthy cells can cause side effects like hair loss, mouth sores, and an increased risk of infection. Your medical team will help you manage any side effects you have.

Chemotherapy for CLL is often combined with monoclonal antibodies or targeted drugs.

Monoclonal antibodies

Antibodies are immune system proteins that help your body find and kill cancer cells. Monoclonal antibodies are synthetic antibodies that attach to proteins on the surface of cancer cells, alerting your immune system to find and destroy the cancer.

Examples of monoclonal antibodies include:

  • alemtuzumab (Campath)
  • obinutuzumab (Gazyva)
  • ofatumumab (Arzerra)
  • rituximab (Rituxan)

You may get these drugs together with chemotherapy as second-line CLL treatment.

Side effects include:

  • itching or redness at the injection site
  • chills
  • fever
  • rash
  • tiredness
  • nausea
  • headache

Because monoclonal antibodies work on your immune system, they can increase your risk of certain infections. If you've had hepatitis B in the past, there’s a chance that the virus could reactivate.

Targeted drugs

These drugs target certain proteins or other substances that help cancer cells grow. Examples of targeted drugs for CLL include:

  • duvelisib (Copiktra)
  • ibrutinib (Imbruvica)
  • idelalisib (Zydelig)
  • venetoclax (Venclexta)

You’ll get these drugs alone, or together with monoclonal antibodies.

Common side effects of targeted drugs include:

  • diarrhea
  • nausea
  • constipation
  • fever
  • tiredness
  • cough
  • shortness of breath
  • joint and muscle aches
  • rash
  • low blood cell counts

Stem cell transplant

If your cancer doesn’t respond to these treatments and you’re in good health, your doctor might recommend a stem cell transplant. A stem cell transplant allows you to get high doses of chemotherapy to kill more cancer cells.

Getting high-dose chemotherapy damages bone marrow to the point where you can’t make enough new blood-forming cells. To replace the cells damaged by treatment, you’ll get healthy stem cells from a donor. A stem cell transplant could improve your outlook.

Treating minimal residual disease

Some people still have a few cancer cells left in their blood, bone marrow, or lymph nodes after their first treatment. This condition is called minimal residual disease (MRD).

Doctors sometimes use the chemotherapy drug Campath to treat people with MRD. It’s not clear whether getting treated right away will improve your outcome. If you have MRD, discuss your options with your doctor.

Clinical trials

CLL isn’t curable. However, treatments have improved enough to keep people in remission — in some cases for a long time. If standard medications no longer work for you, consider joining a clinical trial.

Clinical trials are studies that test out new drugs or combinations of drugs. These new treatments may work better for you than the ones currently available. Ask the doctor who treats your CLL if a clinical trial might be right for you.

Takeaway

If the first treatment you get for CLL doesn’t work or stops working, your doctor will try a second-line therapy. Chemotherapy, monoclonal antibodies, and targeted therapies are all used as secondary treatments for CLL, either alone or in combinations.

You may need to try out a few different treatments to find one that works for you. If none of the treatments you’ve tried has stopped your cancer, ask your doctor if you can enroll in a clinical trial of a new CLL therapy.