As the science of chronic lymphocytic leukemia has advanced, we have learned much more detailed information about its biology and the specific chromosomes, genes, and proteins that contribute to the disease. Checking for specific abnormalities in chromosomes and genetic variants can help doctors evaluate a patient’s prognosis and predict what treatments might work best.
At the International Workshop on CLL (iwCLL) 2019, our own Dr. Brian Koffman interviewed Dr. Nicole Lamanna, an Associate Clinical Professor of Medicine at Columbia University Medical Center. They discussed the role of biomarker testing in CLL and the importance of testing before treatment.
Takeaways:
- Biomarker tests can help predict which patients will do well on or fail certain medications.
- The three most important biomarker tests for CLL are:
- FISH (fluorescence in situ hybridization) tests for common chromosomal abnormalities. These include deletion of the short arm of chromosome 17 (del[17p]), which causes resistance to standard chemo-immunotherapy.
- IGHV (immunoglobulin heavy chain variable gene) mutation status. Patients with a “mutated” IGHV respond better to fludarabine, cyclophosphamide, and rituximab (FCR) chemo-immunotherapy. IGHV mutation status almost never changes over time, so it should only be performed once.
- Genetic testing for mutations in the TP53 gene, which is located on the short arm of chromosome 17. TP53 is an important tumor suppressor gene that normally puts the brakes on cancer growth. If it is missing or dysfunctional the CLL will be harder to manage.
- These tests should be done before beginning initial treatment at a minimum. FISH and TP53 tests should be performed before every subsequent treatment.
- Community practices may have in-house testing capabilities or they may need to send the blood work to an outside lab for testing.
- Doctors can order these tests as part of a gene panel or individually; it depends on the practice.
- FISH testing can be done by most physicians in the community. Mutational testing, such as for TP53, is becoming more standard in community practices. Molecular testing is more advanced and may need to be sent to a specialized lab.
- Reimbursement by insurance for these tests is usually not an issue.
Conclusions:
Biomarker testing provides key information that allows doctors and patients to make informed decisions about which therapies offer the best chance of success. It is critical to get these tests done before starting treatment. In the past, genetic testing may not have made sense because our understanding of the biology of CLL was limited. Now we know a lot more about the specific genetic variants that influence the progression of CLL and the specific proteins that can be targeted with therapies. So it makes a lot more sense to order these specific tests.
For more information about biomarker testing, please check out our Test Before Treat™ webpage.
Please enjoy this interview with Dr. Lamanna from September 2019 at iwCLL in Edinburgh, Scotland.
Take care of yourself first.
Ann Liu, PhD
