Beginning Treatment for CLL
Treatment of CLL is started when symptoms develop that are associated with active disease. Before starting treatment, it is important to have another FISH test to see if there are any changes to the genes and/or chromosomes of the CLL cells.
Because CLL is typically a disease of older people, the doctor will also evaluate a patient’s fitness and identify other medical conditions or problems that may affect CLL treatment.
After these tests are done, CLL patients are most often placed into one of two categories based on mutation status.
Treatment Options by Mutation Status
Patients without del(17p) or TP53 Mutations
The first, or preferred, treatments prescribed to many patients in this category include acalabrutinib, zanubrutinib or venetoclax in combination with obinutuzumab. Another recommended treatment is ibrutinib. For patients with IGHV-mutated CLL under age 65 years without significant comorbidities, FCR (fludarabine, cyclophosphamide, rituximab) is an option.
Patients who are prescribed a type of treatment like acalabrutinib, zanubrutinib, or ibrutinib will take the drug until it no longer works or until side effects occur that require them to stop taking it. If one of these drugs causes severe side effects, a patient may be able to try a different one.
Patients with del(17p) or TP53 Mutations
Patients with del(17p) or TP53 mutations, whether young or older, typically do not respond well to treatment or are likely to have early relapses if the first treatment is any type of chemoimmunotherapy. Treatment with targeted therapies or monoclonal antibodies generally has better results. The treatments below are for patients with del(17p) and should be considered as a first option.
Preferred treatments:
- Acalabrutinib
- Obinutuzumab
- Venetoclax
- Zanubrutinib
Other recommended treatment:
- Ibrutinib
For certain patients who can’t take acalabrutinib, zanubrutinib, or ibrutinib and venetoclax or who need fast disease control, using obinutuzumab or high-dose methylprednisolone with either rituximab or obinutuzumab are options.
If these treatments are not appropriate or effective, a clinical trial should be considered. Allogeneic stem cell transplantation may also be a treatment option.
For information about the drugs listed on this page, visit Drug Listings.
Targeted Therapy
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®)
Monoclonal Antibody Therapies
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).
Chemotherapy
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.
Corticosteroids
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.
Chemoimmunotherapy
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 Drug Listings.
Related Links
- Chemotherapy and Other Drug Therapies
- Measuring treatment response
- Managing Side Effects
- Download or order The Leukemia & Lymphoma Society's free booklet, Chronic Lymphocytic Leukemia