Chronic lymphocytic leukemia (CLL) treatment

These treatments are designed to target (attack) specific substances on cancer cells with less harm to normal, healthy cells. Most targeted therapies for CLL are given as pills and, in general, have milder side effects than chemotherapy.  

Targeted therapies approved for CLL include:  

• Acalabrutinib (Calquence®)
• Zanubrutinib (Brukinsa®)
• Ibrutinib (Imbruvica®)
• Idelalisib (Zydelig®)
• Duvelisib (Copiktra®)
• Venetoclax (Venclexta®)
• Pirtobrutinib (Jaypirca®) 

For information about the drugs listed on this page, visit our cancer drug listing. 

These treatments use immune-system proteins (antibodies) that are made in the lab. Monoclonal antibody therapies aim for a specific target on the surface of the CLL cells. The antibodies attach to the CLL cells so that the immune system can find and kill the CLL cells. In general, the side effects are milder than the side effects of chemotherapy.

Monoclonal antibody therapies used to treat people with CLL include: 

• Obinutuzumab (Gazyva®)
• Rituximab (Rituxan®)
• Rituximab plus hyaluronidase (Rituxan Hycela®)  

With the exception of Rituxan Hycela, which is given by injection subcutaneously (beneath the skin), the rest of these therapies are given intravenously (through an IV line). 

For information about the drugs listed on this page, visit our cancer drug listing. 

Chemotherapy drugs are designed to kill cancer cells. Some drugs are given by mouth (like a pill). Other drugs are given through an IV line. Two or more drugs are often used together. Chemotherapy drugs used to treat some people with CLL include: 

• Fludarabine (Fludara®)
• Cyclophosphamide (Cytoxan®)
• Bendamustine hydrochloride (Bendeka®)
• Chlorambucil (Leukeran®) 

Learn more about chemotherapy or for more information about the drugs listed on this page, visit our cancer drug listing.

Corticosteroids are hormones made in the body. They can also be made in the laboratory and are used to treat certain leukemias and lymphomas.  

Methylprednisolone, a corticosteroid, may be given to treat some people with CLL.  

This type of therapy combines chemotherapy with immunotherapy. Immunotherapy is a type of treatment that uses a person's immune system to help fight cancer. Examples of these are: 

• FCR: fludarabine, cyclophosphamide, and rituximab
• BR: bendamustine and rituximab 

For information about the drugs listed on this page, visit our cancer drug listing. 

The spleen is an organ on the left side of the body, near the stomach. CLL cells can collect in the spleen, causing it to become enlarged. Sometimes, the spleen becomes so large that it presses on nearby organs, causing pain. Also, an enlarged spleen may lower a person’s blood cell counts to dangerous levels. An operation to remove the spleen is called a splenectomy. Splenectomy is helpful for select patients. The operation may reduce pain and help improve blood counts.

This treatment uses X-rays or other high-energy rays to kill cancer cells. Radiation therapy is sometimes used to treat a person with CLL who has an enlarged (swollen) lymph node, spleen, or other organ that is blocking the function of a neighboring body part, such as the kidney or the throat. 

Taking part in a clinical trial may be the best treatment choice for some CLL patients. Clinical trials are underway to improve remission rates for CLL. Today's standard treatments for cancer are based on earlier clinical trials. LLS continues to invest funds in CLL research. 

Learn more about clinical trials.  

In about 2 percent to 10 percent of people with CLL, the disease transforms into something more complex. Of this small group, 95 percent may develop diffuse large-B cell lymphoma (DLBCL), and the other 5 percent may develop Hodgkin lymphoma. This is known as “Richter transformation” or “Richter’s syndrome.” This syndrome is much more common in patients with high-risk factors. These include advanced-stage CLL according to the Rai system assessment; deletion of the short arm of chromosome 17 (del[17p]), trisomy 12, TP53 or NOTCH1 mutations; and IGHV-unmutated CLL.

Richter transformation generally occurs between two to six years after a diagnosis of CLL. Patients may have significantly enlarged lymph nodes and may experience fevers and weight loss. Lymphocyte masses may also develop in parts of the body other than the lymph nodes. This transformation is less common in patients who do not receive chemoimmunotherapy for treatment of their CLL.

Patients with Richter transformation whose CLL has transformed into DLBCL are treated with regimens designed for DLBCL. Allogeneic stem cell transplantation can also be considered following a response to initial therapy. 

Standard Hodgkin lymphoma therapy is used for patients with Richter transformation whose CLL has transformed to Hodgkin lymphoma. With aggressive therapy, these patients tend to do better and may be cured of this condition (although not the underlying CLL). 

Some treatment responses have been reported in recent studies with the use of CAR T-cell therapy for CLL patients with Richter transformation. Treatment in a clinical trial should be considered for these patients. If remission is achieved, these patients should consider an allogeneic stem cell transplant, which is the only curative option. 

Autoimmune cytopenias are conditions in which the immune system attacks the blood cells. Autoimmune cytopenias occur in 4 percent to 10 percent of patients with CLL. The most frequent autoimmune cytopenias in CLL patients are:

• Autoimmune hemolytic anemia (AIHA)
• Immune-mediated thrombocytopenia (also known as “immune thrombocytopenic purpura” or ITP)
• Pure red blood cell aplasia (PRCA) 

AIHA is the most common form of autoimmune cytopenia. Patients who have AIHA produce antibodies that work against their own cells. These “autoantibodies” are usually directed against the patient’s red blood cells and cause them to be removed rapidly from the blood. The loss of these red blood cells can worsen the effects of already low red blood cell counts.

Bone marrow tests may be helpful to confirm the presence of these conditions. The drugs prednisone, rituximab, and cyclosporine are sometimes used to treat AIHA and ITP. The drugs romiplostim (Nplate®) and eltrombopag (Promacta®) are both approved by the FDA for the treatment of ITP that is resistant to other treatments. Splenectomy may be considered for treatment of AIHA and ITP in patients who do not respond to drug therapy.

For information about the drugs listed on this page, visit our cancer drug listing. 

Tumor flare is a drug-related, painful enlargement of the lymph nodes that may be accompanied by elevated lymphocyte counts, an enlarged spleen, low-grade fever, and/or rash and bone pain. 

These reactions are commonly seen in CLL patients treated with lenalidomide (Revlimid®). Use of steroid medications to control inflammation and antihistamines to manage the rash are recommended. 

Tumor lysis syndrome (TLS) is a potentially life-threatening condition that occurs when large amounts of tumor cells are killed at the same time by the cancer therapy, releasing their content into the bloodstream. Patients with very enlarged, “bulky” lymph nodes are considered at high risk for developing TLS, which is best managed if anticipated and TSL therapy is given before treatment for CLL begins. 

Treatment for TLS includes increased hydration, monitoring, and treatment of electrolyte imbalances and abnormal uric acid levels, and therapy with the drug rasburicase (Elitek®), as needed. When starting venetoclax (Venclexta®), it is important to monitor for TLS.

Learn more about TLS.  

People with CLL have a higher risk than people in the general population of developing a second cancer. This may be due to abnormalities in immune function associated with the disease and to the use of chemotherapeutic agents, which can induce potentially long-lasting remissions but are also associated with prolonged immunosuppression. 

The second cancers that are seen most frequently in CLL patients are acute myeloid leukemia, myelodysplastic syndromes, melanoma, gastrointestinal cancer, breast cancer, lung cancer, non-melanoma skin cancer, prostate cancer, kidney cancer, bladder cancer, and head and neck cancers. 

Both treated and untreated people with CLL can develop acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). These complications are more common after treatment with fludarabine and cyclophosphamide (FC) or fludarabine, cyclophosphamide, and rituximab (FCR). 

Although all CLL patients should be counseled about their increased risk for developing a second cancer, studies indicate there are some factors that may help predict the development of other cancers in CLL patients.  

These include:  

• Older age (older than 60 years)
• Males 

It is important to follow up with your oncologist regularly because of the increased risk of second cancers associated with CLL. An annual comprehensive skin examination is also strongly recommended.