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ASH 2020: Dr. Adrian Wiestner Discusses the Importance of Test Before Treat™ Predictive and Prognostic Biomarker Testing in Patients with Chronic Lymphocytic Leukemia (CLL)

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

As the science of chronic lymphocytic leukemia advances, much more detailed information about specific chromosomes, genes, and proteins that contribute to the disease is being discovered through biomarker testing. Checking for specific abnormalities in chromosomes and if any genetic variants are present, is extremely important in determining what treatment options will work best.

At the American Society of Hematology’s (ASH) 2020 conference, there was research on looking at the genome of CLL and how different biomarkers might have predictive value. Dr. Brian Koffman, Chief Medical Officer and Executive Vice President of CLL Society, interviewed Dr. Adrian Wiestner, a senior investigator at the National Institutes of Health in Bethesda, Maryland. They discuss why it is important for all CLL patients to receive biomarker testing before receiving any new CLL / SLL therapies, especially chemotherapy.

More and more genetic mutations are being discovered. But many only occur in a very small subset of CLL / SLL patients, and we are not sure what the clinical implications of these new discoveries might be. However, what we do know is that all CLL / SLL patients should at a minimum know the results of these three specific biomarker tests prior to beginning their initial treatment:

  1. FISH (fluorescence in situ hybridization) test: This tests for the more common chromosomal abnormalities that are present with CLL, which include deletion of the short arm of chromosome 17 (del17p). Those with del17p should NOT receive standard chemo-immunotherapy because it will not work.
  2. IGHV (immunoglobulin heavy chain variable gene) mutation status: Patients with mutated IGHV status respond better to FCR (fludarabine, cyclophosphamide, and rituximab) chemo-immunotherapy. It is important to note that IGHV mutation status does not change over time, so testing for this status only needs to be performed once.
  3. TP53 gene mutation status: TP53 is an important tumor suppressor gene that normally puts the brakes on cancer growth. If it is missing or dysfunctional, CLL will be harder to manage.

It is important to note that FISH and TP53 testing should be performed before every subsequent change in treatment, as the status of these can change over time. However, the IGVH test only needs to be performed once because it does not change. For more information about the need for testing and retesting in CLL, please click here.

Additionally, CLL Society has a one-page reference sheet that can be printed and shared with providers regarding the importance of our TEST BEFORE TREAT™ awareness campaign.


  • Biomarker testing can help predict which patients will do well or fail certain medications.
  • One can think of chromosomes as the 23 chapters in the book that may up the instructions for life, and the gene as the specific building plans.
  • The three most important genetic biomarker tests for CLL / SLL are FISH, IGHV, and TP53 status.
  • Patients who are not getting appropriately tested, and that is still happening too often, may not be getting appropriately treated.
  • Patents should ask, “Would it be important to know my TP53, IGVH, and my del17p status?”
  • No CLL / SLL patient should receive chemotherapy if they have not first had biomarker testing.


  • There are now many incredible diagnostic tools that can help guide CLL treatment but they must be utilized.
  • Many community hematologists are not aware of the importance of knowing the status of CLL biomarkers.
  • Patients must advocate on their own behalf and request genetic testing be performed prior to treatment.
  • Increasing awareness about the importance of knowing CLL / SLL biomarker status is critical in achieving the best outcomes.

Enjoy this interview between Dr. Brian Koffman and Dr. Adrian Wiestner:

To learn what multiple CLL experts have to say about the importance of performing these important tests, visit the CLL Society Website.

Keep learning, be kind, and stay well!

Robyn Brumble, MSN, RN
Director of Scientific Affairs
CLL Society