Chemotherapy and Drug Therapy

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 treatments prescribed to many patients in this category include acalabrutinib, zanubrutinib, or venetoclax in combination with obinutuzumab. Other recommended treatment options for patients without del(17p) or TP53 mutations are included in the table below. 

First-Line Therapy 

Preferred Regimens  Other Recommended Regimens  Useful in Certain Circumstances (Consider for IGHV-mutated CLL in Patients <65 years without significant comorbidities) 
  • Acalabrutinib± obinutuzumab 
  • Venetoclax + obinutuzumab 
  • Zanubrutinib 
  • Ibrutinib 
  • Bendamustine + anti-CD20 monoclonal antibody therapy 
  • Chlorambucil + obinutuzumab 
  • Obinutuzumab 
  • High-dose methylprednisolone + rituximab or obinutuzumab 
  • Ibrutinib + obinutuzumab 
  • Ibrutinib + rituximab 
  • Ibrutinib + venetoclax 
  • FCR (fludarabine, cyclophosphamide, rituximab) 

Source: NCCN (National Comprehensive Cancer Network) Clinical Practice Guidelines in Oncology. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. 2023. 

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 chemo-immunotherapy. Treatment with targeted therapies or monoclonal antibodies generally has better results. The treatments in the table below are for patients with del(17p) and should be considered as a first option. 

First-Line Therapy 

Preferred Regimens  Other Recommended Regimens 
  • Acalabrutinib± obinutuzumab 
  • Venetoclax + obinutuzumab 
  • Zanubrutinib 
  • High-dose methylprednisolone + rituximab 
  • Ibrutinib 
  • Obinutuzumab 
  • Ibrutinib + venetoclax 

Source: NCCN (National Comprehensive Cancer Network) Clinical Practice Guidelines in Oncology. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. 2023. 

For information about the drugs listed on this page, visit Drug Listings.

Targeted Therapies

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®)   

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: 

  • Cladribine (Leustatin®) 
  • 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.

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