Chronic lymphocytic leukemia (CLL) treatment options depend on your diagnosis. In earlier stages, “watchful waiting” may be recommended. More advanced CLL may require a combination of therapies.
Chronic lymphocytic leukemia (CLL) is a cancer that affects your blood and bone marrow. It begins in a type of white blood cell called a B lymphocyte, which plays an important part in your immune response.
CLL is considered chronic because it typically progresses slowly, often taking years before the symptoms become noticeable or need treatment. CLL has two primary types, which have unique genetic characteristics that can affect medical management.
How CLL is treated depends on your diagnosis and individual factors such as your overall health, age, and lifestyle.
“Watch and wait” is a conservative approach to treating CLL in its early stages. As a slow-growing cancer, CLL can take years to begin to cause symptoms or affect your daily life.
Cancer drugs and therapies can be demanding on your body and often come with serious side effects. When CLL isn’t causing symptoms, doctors recommend watching and waiting rather than aggressively treating the cancer.
During conservative treatment, you’ll still have regular CLL checkups and screenings. Doctors will monitor your lymph nodes, organs, and blood counts to track CLL progression.
There’s no evidence that watching and waiting negatively affects CLL outcomes.
Targeted and other drug therapies are cornerstones of CLL treatment. Your treatment may include multiple types of cancer drugs, depending on your individual diagnosis. A doctor will consider individual factors and the genetic features of a CLL diagnosis to determine the best medication options.
Targeted therapies
Aside from observation, targeted drug therapies are the most common treatment for CLL. These therapies work by interfering with specific molecular pathways that are necessary for cancer cells to survive and spread.
Targeted drug therapies for CLL include:
- Bruton tyrosine kinase (BTK) inhibitors: These drugs inhibit the protein BTK, which helps CLL cells grow and spread. Examples include ibrutinib, acalabrutinib, zanubrutinib, and pirtobrutinib.
- BCL-2 inhibitors: These drugs block the protein BCL-2, which helps cancer cells live longer than they should. One example is venetoclax.
- Phosphatidylinositol 3-kinases (PI3K) inhibitors: These drugs interrupt the PI3K signaling pathway in cells and interrupt various processes related to cancer cell growth, spread, and survival. Examples include idelalisib and duvelisib.
Immunotherapies
Immunotherapy drugs work by changing immune cells or enhancing your immune response. They’re often separated into their own category of cancer treatments (immunotherapy), but because of their targeted nature, they also fall under the banner of targeted therapies.
The following two types of immunotherapy may be used in CLL treatment:
- Monoclonal antibodies: These drugs work by targeting specific proteins (antigens) on the surface of CLL cells. They can trigger an immune response or inhibit cell growth in other ways. Examples include rituximab, obinutuzumab, ofatumumab, and alemtuzumab.
- Chimeric antigen receptor (CAR) T-cell therapy: For this treatment, special immune cells called T cells are collected from your blood and genetically engineered to target CLL cell antigens, allowing the T cells to kill the cancer cells. An example of a CAR T-cell therapy drug is lisocabtagene maraleucel.
Chemotherapy
Chemotherapy is often given with immunotherapy at the same time. Some CLL patients may receive chemotherapy because of a particular gene mutation or some other circumstance that would keep them from being able to take a targeted therapy safely.
Standard chemotherapy usually involves drugs that are cytotoxic, meaning they kill rapidly dividing cells (both cancerous and noncancerous). Your chemotherapy treatment in CLL will likely consist of more than one chemotherapy drug.
Here are the generic names and brand names of some common chemotherapy drugs that may be used in CLL treatment:
- fludarabine (Fludara)
- cladribine (Leustatin)
- chlorambucil (Leukeran)
- cyclophosphamide (Cytoxan)
Corticosteroids
Corticosteroids are supportive medications that reduce inflammatory processes and suppress autoimmune reactions that are complications of CLL. Methylprednisolone is a common corticosteroid for CLL that’s used in combination with certain immunotherapies.
Radiation therapy is not a common treatment option for CLL. If your doctor recommends it, the most common approach will be
Radiation therapy is typically considered when:
- enlarged organs are causing discomfort and are not shrinking from standard therapies
- your bone marrow is being prepared for a stem cell transplant
Also, a single or small group of lymph nodes without any other sign of disease would likely be given radiation to treat before starting medications.
When you have CLL, your spleen can become enlarged as a result of the buildup of abnormal B lymphocytes, which continue to grow within the organ.
In very rare cases, if the enlargement can’t be successfully managed with medication or radiation, your spleen may need to be surgically removed through a procedure called a splenectomy.
Splenectomy is rarely done, and it’s not done for the CLL itself but for a complication of it called autoimmune hemolytic anemia (AIHA). The spleen will destroy platelets, so a doctor will remove the spleen to help platelet counts.
Stem cells act as the building blocks for cellular regeneration. Stem cell transplants (SCTs) use implanted stem cells to help replace bone marrow tissue that is unhealthy as a result of CLL.
There are two types of SCTs. During an allogeneic SCT, you receive stem cells from a donor. During an autologous SCT, you receive your own stem cells, which have been extracted and stored for use after high dose chemotherapy.
SCTs are considered a secondary line of treatment in CLL. They’re primarily used when there’s a high chance that the cancer will come back after treatment or when CLL is resistant to other therapies.
Novel therapies are emerging areas of innovation in the treatment of CLL. They might involve new drug formulations, unique drug combinations, or new therapeutic agents that target the life span of CLL cells.
Novel therapies currently being investigated in research include:
- New small molecule targets (CDK9, MCL1, ERK inhibitors): new molecules small enough to infiltrate cancer cells and target specific parts of CLL development and progression
- CAR T cells with new antigen targets: genetically engineered T cells that bind to new, more specific receptor sites
- Bispecific antibodies (bispecific T-cell engagers, dual-target antibodies): engineered antibodies that bind simultaneously to two different receptor sites to enhance the immune response against cancer cells
- CAR natural killer (NK) cells: a therapy that’s similar to CAR T-cell therapy but uses NK cells instead
- Other adoptive cell therapy (in vitro Th17 polarization): changing or engineering other types of immune cells (such as TH17 T-helper cells) to better recognize and attack cancer cells
If you’ve received a CLL diagnosis, you may want to consider participating in a clinical trial. CLL progression and severity can vary significantly from person to person, and clinical trials offer the opportunity to try emerging therapies under the supervision of a highly skilled medical team.
While there are typically still costs associated with clinical trials, you may gain access to personalized cancer care at a reduced cost as a study participant.
You can find current clinical trials for CLL by visiting:
Survival outcomes and treatment success vary significantly in CLL. Average survival rates are
For example, if you have early stage, low risk CLL, you may live up to 20 years with just “watch and wait” management.
CLL is
The 5-year relative survival rate is an estimate of how likely someone with a certain condition is to survive for 5 years after diagnosis as compared to someone without that condition. So, an 87% rate means that someone with CLL is 87% as likely to live for 5 years as someone without CLL.
More research is necessary to understand the survival rates, safety, and effectiveness of emerging therapies.
CLL is a type of cancer that affects your blood and bone marrow. It can affect each person differently, and treatment may range from “watch and wait” management to the use of multiple cancer drugs and medical interventions.
To help improve CLL outcomes, researchers are continually studying new therapies through clinical trials and other methods.