Chronic Lymphocytic Leukemia

Treatment Planning

An open physician-patient relationship will be vital to successful CLL treatment. You will work closely with your doctor, who will rely on you to be an active member of the care team. This means communicating when your symptoms begin or change. Although curing the cancer is a goal, “curing CLL” may mean reaching remission with no signs or symptoms of cancer, or managing the disease like a chronic condition. You and your doctor will make shared decisions about treatments and side effect management to help you achieve your desired quality of life.

Treatment Options

Unlike most cancers, treating CLL often does not begin until symptoms or test results indicate it is necessary. This will require you to share how you are feeling so your doctor can determine when to begin treatment.

When it is time to treat, your doctor will ask for your input to develop a treatment plan and discuss possible side effects. You may discuss different approaches. Regardless of your treatment plan, you will be monitored frequently to ensure the treatment is working, and you will be expected to report symptoms and side effects. Commit to taking your treatments and going to your follow-up appointments, which are important for monitoring treatment, addressing side effects or issues, and detecting a recurrence or second cancer early.

Active surveillance is a strategy often re-commended for patients with low-risk or low-stage CLL. Sometimes referred to as watch and wait, this approach delays active treatment until you experience symptoms that affect your quality of life or have lab tests showing blood cell count changes.

Symptoms that should be shared with your doctor because they may indicate your CLL is progressing include the following:

  • Unexplained weight loss
  • Severe fatigue
  • Fevers above 100.4 °F without evidence of infection
  • Drenching night sweats
  • Spleen or lymph node enlargement
  • Shaking; chills
  • Chest pain or shortness of breath
  • Excessive bleeding or bruising; clotting issues

Receiving a cancer diagnosis and not beginning active treatment right away can be stressful. See suggestions below on how to manage the anxiety that often accompanies this treatment strategy.

Clinical trials may be the best first treatment option for your specific diagnosis, even if symptoms do not yet indicate you need treatment. Significant research is underway to find new or improved methods of treating CLL, including chimeric antigen receptor (CAR) T-cell therapy (see Clinical Trials).

Targeted therapy is systemic drug therapy that is commonly used as first-line therapy for CLL. It is used to attack certain cancer cells and avoids healthy cells, resulting in fewer side effects than with traditional chemotherapy. Some may be used alone or in combination with other therapies.

Following are the types used to treat CLL:

  • Tyrosine kinase inhibitors (TKIs) block certain substances that control how cells grow and divide. One type, called a Bruton’s tyrosine kinase (BTK) inhibitor, blocks the BTK protein, which may promote the growth of abnormal B-cells.
  • BCL-2 inhibitors block the BCL-2 protein, a protein found in leukemia cells.
  • Monoclonal antibodies are laboratory-made immune system proteins that attach to a specific target on cancer cells or other cells that may help cancer grow. The antibodies are then able to kill the cancer cells, block their growth or keep them from spreading.

Depending on whether your CLL is high-risk (contains chromosome changes) or low-risk, your doctor will determine which type is best for you. Patients typically continue taking this type of drug therapy until it stops working. It is important to know that using one type of targeted therapy does not eliminate the option of using another if that type fails or becomes less effective (refractory), or if a relapse occurs.

Corticosteroids, anti-inflammatory drugs that appear to help cause the death of cancerous white blood cells, are sometimes given along with other drug therapies.

Radiation therapy may be used to shrink an enlarged spleen or swollen lymph nodes, relieve certain symptoms or as part of the conditioning phase of a stem cell transplant.

An allogeneic stem cell transplant, which uses stem cells from a volunteer donor, may be used to treat very specific cases of CLL. The goal of transplantation is for your blood counts to return to safe levels and/or remission. For details about transplants, visit:

Chemotherapy destroys cancer cells by preventing them from growing and dividing. It may be used in some instances and combined with other therapies. It may be given in high doses before a stem cell transplant in a process known as conditioning.

Surgery may be used to remove an enlarged spleen (splenectomy).

Relapsed and Refractory CLL

Even after reaching remission, CLL may return in different ways.

Relapsed (or recurrent) CLL is cancer that has returned, usually after a period of time during which it cannot be detected. If this occurs, your doctor will begin a new cycle of diagnostic tests to confirm whether the cancer is recurrent and whether it has transformed into a more aggressive subtype, which may change your treatment plan.

Refractory CLL is cancer that does not respond to or improve with treatment. Your doctor will consider the approaches you have already tried before recommending another plan. If your doctor does not specialize in CLL, get a second opinion to ensure you learn about all your options, including clinical trials.

Drug Therapies for CLL
These therapies may be used alone or in combination. Possible combination therapies are listed below.
acalabrutinib (Calquence)
bendamustine (Belrapzo, Bendeka, Treanda, Vivimusta)
chlorambucil (Leukeran)
duvelisib (Copiktra)
fludarabine phosphate (Fludara)
ibrutinib (Imbruvica)
idelalisib (Zydelig)
obinutuzumab (Gazyva)
ofatumumab (Arzerra)
rituximab (Rituxan)
rituximab and hyaluronidase human (Rituxan Hycela)
venetoclax (Venclexta)
zanubrutinib (Brukinsa)
Some Possible Combinations
acalabrutinib (Calquence) and obinutuzumab (Gazyva)
BR: bendamustine (Bendeka) and rituximab (Rituxan)
FC: fludarabine phosphate and cyclophosphamide
FCR: fludarabine phosphate, cyclophosphamide and rituximab (Rituxan) or rituximab and hyaluronidase human (Rituxan Hycela)
FR: fludarabine phosphate and rituximab (Rituxan)
ibrutinib (Imbruvica) with bendamustine (Bendeka) and rituximab (Rituxan)
ibrutinib (Imbruvica) with rituximab (Rituxan)
idelalisib (Zydelig) and rituximab (Rituxan) for patients with recurrent CLL
obinutuzumab (Gazyva) and chlorambucil (Leukeran) for older patients
ofatumumab (Arzerra) and chlorambucil (Leukeran)
ofatumumab (Arzerra) with fludarabine and cyclophosphamide
rituximab and hyaluronidase human (Rituxan Hycela) with fludarabine and cyclophosphamide
VEN+G: venetoclax (Venclexta) with obinutuzumab (Gazyva)
VEN+R: venetoclax (Venclexta) with rituximab (Rituxan)
As of 9/28/23

What to do during active surveillance

Being told to watch and wait for your CLL to progress before starting treatment can understandably cause anxiety and impatience. You may want to start treatment as soon as possible because waiting to treat may seem counter-intuitive. However, the reason for this approach is that studies looking at early treatment soon after diagnosis have historically failed to demonstrate an improvement in survival and may cause additional side effects.

Following are some things to do to be proactive during active surveillance:

  • Make sure your vaccinations are up to date.
  • Assemble a good multidisciplinary health care team that you are comfortable with.
  • Create layers of support around you, including friends, family, and in-person or online support groups. Talking to other people who are in a similar situation can be valuable.
  • Always think several steps ahead of CLL. Ask your doctor how potential relapses and refractory CLL will be managed in the future and whether you might be a good candidate for clinical trials.
  • Know your molecular profile. Doctors are increasingly relying on this information as guidance for how aggressively to treat your CLL. Know whether you have high-risk or low-risk disease.
  • Seek a second opinion.

Following are some ideas of what NOT to do while you wait:

  • Don’t panic. Research has shown that starting treatment early does not improve outcomes.
  • Don’t isolate yourself. Being alone can worsen your mental health and increase anxiety.
  • Don’t miss follow-up appointments. These will be key in determining when it is time to start treatment.
  • Don’t miss follow-up appointments. These will be key in determining when it is time to start treatment.
  • Don’t ignore symptoms. Your doctor will rely on you to communicate how you are feeling.
  • Don’t forget to make healthy eating a priority and incorporate daily physical activity.
  • Don’t stop socializing and enjoying your life.
  • Don’t stop learning about CLL, its treatments and possible clinical trials

Terms to know

Complete remission: All signs and symptoms of cancer have disappeared, but cancer may still be in the body.

Partial remission: Leukemia levels are significantly reduced, but there is still evidence of some leukemia cells.

Minimal residual disease (MRD): A term used to describe a very small number of cancer cells that remain in the body during or after treatment. Specialists use highly sensitive laboratory tests to find one cancer cell among one million normal cells. This information helps your doctor to plan further treatment and monitor you to determine whether the treatment is working or if cancer has returned.

  • Unexplained weight loss
  • Severe fatigue
  • Fevers above 100.4° F without evidence of infection
  • Drenching night sweats
  • Spleen or lymph node enlargement
  • A decreasing number of red blood cells or platelets
  • Treatment with steroids is no longer working and your body is killing your blood cells (autoimmune cytopenia)
  • Even if symptoms don’t yet indicate you need treatment, you may choose to enroll in a clinical trial.