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Chronic lymphocytic leukemia (CLL) can often be put into remission (partial or full reduction of CLL signs or symptoms) with newer non-chemotherapy targeted treatments listed below. With the current therapy options, CLL does, however, often resurface after several years following treatment. If CLL signs and symptoms get to the point that a patient qualifies for treatment again, they can choose another line of therapy to once again achieve remission. 

About 1/3 of CLL patients will need treatment at the time of diagnosis, 1/3 may not need treatment immediately but will later on, and the remaining 1/3 may never need treatment as CLL often progresses slowly. 

Treatment for CLL begins once one of the following issues arises:

(Image source: NCCN Guidelines for CLL Patients)

If one of the above signs or symptoms is not present, CLL treatment does not start. Rather, the patient and their care team monitor the patient's health over time called the "watch and wait" or "active observation" period. Patients are encouraged to live their lives as normal and keep in contact with their medical team regarding any concerns they may have. The reason behind choosing watch and wait as opposed to beginning treatment at the time of diagnosis without signs present is because the length and health-related quality of patient life has not been found to be impacted by waiting. 

Once signs arise to a point that requires treatment, below are non-chemo CLL treatment paths patients can expect whether for first-time or follow-up therapy (as of 2023 per NCCN guidelines). Medicine names with a brief description are listed, followed by preferred CLL treatment paths. Treatment paths are separated by if the patient does or does not have a deletion of chromosome 17p in their CLL cells (del[17p])/TP53 mutation.  

To get the most accurate care for your CLL, find your CLL specialist. Need help? Take a look at HealthTree’s CLL Specialist Directory to locate an expert near you. The directory is currently for U.S.based practitioners, however, HealthTree is working on compiling a global version. If you live outside of the U.S. and need help finding a CLL specialist, please email cll@healthtree.org. Need financial support to visit a specialist (travel costs, housing costs, medicine costs)? Click here for financial options to help get the treatment you need. 

Non-Chemo Treatment Names and Descriptions 

  • Venetoclax (Venclexta): BCL-2 inhibitor targeted therapy
    • Taken in tablets by mouth for ~12 months (previously untreated CLL) or ~24 months (previously treated CLL)
    • More info about venetoclax 
  • Zanubrutinib (Brukinsa): Covalent BTK inhibitor targeted therapy 
  • Acalabrutinib (Calquence): Covalent BTK inhibitor targeted therapy 
    • Taken in tablets by mouth as needed
    • More info about acalabrutinib
  • Obinutuzumab (Gazyva): Antibody targeted therapy 
  • Rituximab (Rituxan): Antibody targeted therapy 
    • Administered by infusion 
    • More info about rituximab

Possible CLL Treatment Paths 

The following are all non-chemo treatment options. Chemotherapy is rarely used to treat CLL thanks to recent medical advances. 

PATIENT DOES NOT HAVE DEL(17P)/TP53 MUTATION

First time being treated (one of the following): 

  • Venetoclax with obinutuzumab 
  • Zanubrutinib taken by itself 
  • Acalabrutinib with or without obinutuzumab 

Second and third-line regimens:

  • If the first treatment was a BTK inhibitor
    • Use venetoclax with obinutuzumab (if your insurance allows using obinutuzumab over another medicine called rituximab when treating a second time) 
    • If the first BTKi tried was not acalabrutinib or zanubrutinib, then try one of those
  • If the first treatment was venetoclax alone
    • Use venetoclax with obinutuzumab if the cancer had been in remission
    • Acalabrutinib or zanubrutinib
  • If the first treatment was chemoimmunotherapy or immunotherapy 
    • Use venetoclax with obinutuzumab 
    • Acalabrutinib or zanubrutinib

If BTK inhibitors and venetoclax don’t work:

PATIENT HAS DEL(17P)/TP53 MUTATION

First time being treated (one of the following): 

  • Venetoclax with or without obinutuzumab
  • Zanubrutinib taken by itself 
  • Acalabrutinib with or without obinutuzumab 

Second and third-line regimens for CLL with del(17p)/TP53 mutation:

  • Venetoclax with rituximab or venetoclax alone 
  • Zanubrutinib
  • Acalabrutinib 

If BTK inhibitors and venetoclax don’t work:

Commonly Asked Questions

Why are some medicines used in a combination? 

  • Data has shown some medicines are more effective at reducing CLL cancer cells when used in combination with another type of treatment

What are 17p deletion and TP53 mutation? 

  • 17p deletion [del(17p)] means a portion of chromosome 17 is deleted. That deleted portion of chromosome 17 contains a gene called TP53. TP53 contains instructions to build protein p53. P53 is used to repair damaged DNA and start the process for cells beyond repair to die
  • Sometimes chromosome 17 is not deleted, however, the TP53 gene in chromosome 17 is mutated causing it to not work as it should. If you have del(17p)/TP53 mutation, you may need to start CLL treatment soon as this type of CLL progresses more quickly than others. 
  • Tests your doctor will complete to check for del(17p)/TP53 mutation include: 

Chronic lymphocytic leukemia (CLL) can often be put into remission (partial or full reduction of CLL signs or symptoms) with newer non-chemotherapy targeted treatments listed below. With the current therapy options, CLL does, however, often resurface after several years following treatment. If CLL signs and symptoms get to the point that a patient qualifies for treatment again, they can choose another line of therapy to once again achieve remission. 

About 1/3 of CLL patients will need treatment at the time of diagnosis, 1/3 may not need treatment immediately but will later on, and the remaining 1/3 may never need treatment as CLL often progresses slowly. 

Treatment for CLL begins once one of the following issues arises:

(Image source: NCCN Guidelines for CLL Patients)

If one of the above signs or symptoms is not present, CLL treatment does not start. Rather, the patient and their care team monitor the patient's health over time called the "watch and wait" or "active observation" period. Patients are encouraged to live their lives as normal and keep in contact with their medical team regarding any concerns they may have. The reason behind choosing watch and wait as opposed to beginning treatment at the time of diagnosis without signs present is because the length and health-related quality of patient life has not been found to be impacted by waiting. 

Once signs arise to a point that requires treatment, below are non-chemo CLL treatment paths patients can expect whether for first-time or follow-up therapy (as of 2023 per NCCN guidelines). Medicine names with a brief description are listed, followed by preferred CLL treatment paths. Treatment paths are separated by if the patient does or does not have a deletion of chromosome 17p in their CLL cells (del[17p])/TP53 mutation.  

To get the most accurate care for your CLL, find your CLL specialist. Need help? Take a look at HealthTree’s CLL Specialist Directory to locate an expert near you. The directory is currently for U.S.based practitioners, however, HealthTree is working on compiling a global version. If you live outside of the U.S. and need help finding a CLL specialist, please email cll@healthtree.org. Need financial support to visit a specialist (travel costs, housing costs, medicine costs)? Click here for financial options to help get the treatment you need. 

Non-Chemo Treatment Names and Descriptions 

  • Venetoclax (Venclexta): BCL-2 inhibitor targeted therapy
    • Taken in tablets by mouth for ~12 months (previously untreated CLL) or ~24 months (previously treated CLL)
    • More info about venetoclax 
  • Zanubrutinib (Brukinsa): Covalent BTK inhibitor targeted therapy 
  • Acalabrutinib (Calquence): Covalent BTK inhibitor targeted therapy 
    • Taken in tablets by mouth as needed
    • More info about acalabrutinib
  • Obinutuzumab (Gazyva): Antibody targeted therapy 
  • Rituximab (Rituxan): Antibody targeted therapy 
    • Administered by infusion 
    • More info about rituximab

Possible CLL Treatment Paths 

The following are all non-chemo treatment options. Chemotherapy is rarely used to treat CLL thanks to recent medical advances. 

PATIENT DOES NOT HAVE DEL(17P)/TP53 MUTATION

First time being treated (one of the following): 

  • Venetoclax with obinutuzumab 
  • Zanubrutinib taken by itself 
  • Acalabrutinib with or without obinutuzumab 

Second and third-line regimens:

  • If the first treatment was a BTK inhibitor
    • Use venetoclax with obinutuzumab (if your insurance allows using obinutuzumab over another medicine called rituximab when treating a second time) 
    • If the first BTKi tried was not acalabrutinib or zanubrutinib, then try one of those
  • If the first treatment was venetoclax alone
    • Use venetoclax with obinutuzumab if the cancer had been in remission
    • Acalabrutinib or zanubrutinib
  • If the first treatment was chemoimmunotherapy or immunotherapy 
    • Use venetoclax with obinutuzumab 
    • Acalabrutinib or zanubrutinib

If BTK inhibitors and venetoclax don’t work:

PATIENT HAS DEL(17P)/TP53 MUTATION

First time being treated (one of the following): 

  • Venetoclax with or without obinutuzumab
  • Zanubrutinib taken by itself 
  • Acalabrutinib with or without obinutuzumab 

Second and third-line regimens for CLL with del(17p)/TP53 mutation:

  • Venetoclax with rituximab or venetoclax alone 
  • Zanubrutinib
  • Acalabrutinib 

If BTK inhibitors and venetoclax don’t work:

Commonly Asked Questions

Why are some medicines used in a combination? 

  • Data has shown some medicines are more effective at reducing CLL cancer cells when used in combination with another type of treatment

What are 17p deletion and TP53 mutation? 

  • 17p deletion [del(17p)] means a portion of chromosome 17 is deleted. That deleted portion of chromosome 17 contains a gene called TP53. TP53 contains instructions to build protein p53. P53 is used to repair damaged DNA and start the process for cells beyond repair to die
  • Sometimes chromosome 17 is not deleted, however, the TP53 gene in chromosome 17 is mutated causing it to not work as it should. If you have del(17p)/TP53 mutation, you may need to start CLL treatment soon as this type of CLL progresses more quickly than others. 
  • Tests your doctor will complete to check for del(17p)/TP53 mutation include: 

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