Chronic Lymphocytic Leukemia

Treatment Planning

The goal of treatment for chronic lymphocytic leukemia (CLL) is to reach remission — no signs or symptoms of cancer. Currently, CLL is managed like a chronic disease. Although there is no cure for CLL at this time, research continues to uncover new and better ways of treating it, and more treatment options are available today with more expected in the coming years. Keep in mind that your treatment plan will likely change as the disease changes to ensure it continues to be managed most effectively.

When you are first diagnosed with CLL, your immediate reaction may be to start treatment right away while you feel healthy enough to do so. But unless you are experiencing certain symptoms or your blood test results deem it necessary, your doctor may recommend waiting to begin treatment to spare you from side effects that could disrupt your quality of life. Unlike other cancers that are aggressive and may need immediate treatment, research shows that treating CLL early does not improve the outcome.

Instead of beginning treatment with medication, you and your medical team will monitor your condition together during what’s called active surveillance, sometimes referred to as watchful waiting. It is often recommended for low-stage or low-risk CLL.

You may find this treatment approach unsettling because it feels as if you are not taking action. However, being a responsible patient and doing your part is taking action.

As your medical team monitors you through tests and physical exams, you will be responsible for keeping follow-up appointments and alerting your medical team immediately if you experience any symptoms that indicate the disease is progressing. Some symptoms and reasons to start treatment include the following:

  • Unexplained weight loss
  • Sever 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

Treatment Options

Clinical trials may offer access to leading-edge therapies not yet approved by the U.S. Food and Drug Administration. They may also be the best first treatment option for your specific diagnosis. Clinical trials are studies that evaluate whether a new treatment, such as a drug or vaccine, drug combination, surgical procedure, type of radiation therapy or a combination of therapies is more effective or better in some way than the current standard of care. A great deal of progress continues to be made in the ways doctors treat CLL, including trials using chimeric antigen receptor (CAR) T-cell therapy.

Targeted therapy is a personalized strategy that enables your doctor to use the results from your genetic (molecular) testing to target specific genes and proteins that are causing cancer cells to grow and multiply.

It is commonly the first treatment given for CLL. Types of targeted therapies used for CLL include the following:

  • 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.
  • BCL2 inhibitors block the BCL2 protein, which is found on some 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.

Using targeted therapy allows your medical team to control the disease while limiting damage to healthy cells, which may result in fewer side effects. Some targeted therapy drugs are oral medications given in pill form, and others are given intravenously (IV). Some may be used alone or in combination with other therapies.

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

Chemoimmunotherapy combines chemotherapy with immunotherapy. It may be used for CLL that does not have the TP53 mutation.

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

Other Treatments

An allogeneic stem cell transplant, which uses stem cells from a volunteer donor, may be used to treat CLL. The goal of transplantation is for your blood counts to return to safe levels and/or remission, which is having no signs or symptoms of cancer.  

Chemotherapy may be used in some instances and combined with other therapies. It may be given in high doses before stem cell transplantation in a process known as conditioning.

Surgery may be recommended in cases where the spleen is enlarged and needs to be removed (splenectomy).

Relapsed and Refractory CLL

Because CLL is a chronic condition, it may return in different ways. Following are descriptions of various states of CLL.

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

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 to determine if the treatment is working or if cancer has returned.

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

Refractory CLL: Cancer that does not respond or improve with treatment. Several options are available to treat refractory CLL. Your doctor will take into account the options you have already tried and your overall health before recommending another plan. This may be a good time to consider getting a second opinion, especially if your doctor doesn’t specialize in CLL. You may also consider clinical trials.

Relapsed (or recurrent) CLL: Cancer that has come back, usually after a period of time during which the cancer could not be detected. If this occurs, your doctor will begin a new cycle of diagnostic tests, which may include another biopsy and laboratory tests. Your doctor will confirm whether the cancer is recurrent and whether it has transformed into a more aggressive subtype, which will affect your new treatment plan.





  • 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.
Drug Therapies for CLL
These therapies may be used alone or in combination. Possible combination therapies are listed below.
acalabrutinib (Calquence)
bendamustine (Bendeka)
chlorambucil (Leukeran)
cyclophosphamide
dexamethasone
doxorubicin hydrochloride (Adriamycin)
duvelisib (Copiktra)
fludarabine phosphate (Fludara)
ibrutinib (Imbruvica)
idelalisib (Zydelig)
methylprednisolone
obinutuzumab (Gazyva)
ofatumumab (Arzerra)
prednisone
rituximab (Rituxan)
venetoclax (Venclexta)
Some Possible Cominations
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 10/13/21

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