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Genomic testing and clinical decision making in CLL – Course 1: The importance of testing

As the treatment of chronic lymphocytic leukemia (CLL) becomes increasingly genomics-driven, performing the appropriate genomic tests and utilizing these results in treatment selection is critical. To optimize patient outcomes, physicians must be aware of how patients’ genomic landscape impacts their response to treatments for CLL.  

Designed to support global healthcare professionals in applying genomic testing, VJAcademy’s course ‘Why is genomic testing important in CLL and what does it mean for patients?is a free-access CME accredited e-learning activity. 

Why use genomic testing?

 

“Molecular techniques have identified somatic genetic alterations, and these can be both relevant in terms of the prognosis through the clinical course of [CLL] but also can be predictive of the response both to chemotherapy and targeted agents,” explains Toby Eyre, MBChB (Hons), MRCP (UK), FRCPath (UK), MD, of the Oxford University Hospitals NHS Foundation Trust, Oxford, UK, in Module 1: Why is genomic testing important in CLL and what does it mean for patients? 

Within this module, Dr Eyre introduces the biology of CLL, its cellular origins and the genomics of its progression. He also describes how some genomic lesions can predict response to treatment: “Patients who do have a tumor protein 53​ gene (TP53) deletion or mutation are known to benefit substantially more from targeted inhibitors such as ibrutinib or venetoclax, whereas they do not derive durable benefit from immunochemotherapy.” 

Dr Eyre adds: “The immunoglobulin heavy chain variable region gene (IGHV) mutation status is also important… patients who receive immunochemotherapy have a substantially worse outcome if they have IGHV unmutated (IGHV-UM) disease, and they derive substantially more benefit from targeted inhibitors. The same is also true for chromosome 11q deletions.” 

 

 

 

Toby Eyre

Toby Eyre, MBChB (Hons), MRCP (UK), FRCPath (UK), MD
Oxford University Hospitals NHS Foundation Trust

How is genomic testing currently used in CLL?

 

 

 

Prioty Islam

Prioty Islam, MD, MSc
Memorial Sloan Kettering Cancer Center

 

In Module 2: Real-world utilization of genomics-driven treatment selection in CLL, Prioty Islam, MD, MSc, of the Memorial Sloan Kettering Cancer Center, New York City, NY, examines the current implementation rates for genomic testing in CLL, and the impact this has on treatment selection using the results of the informCLL Registry. 

The registry catalogued patient characteristics and treatment patterns since the introduction of targeted agents in CLL and revealed that “despite society guidelines regarding baseline and pre-treatment genomic testing in CLL, most patients do not receive genomic testing.” 

Not only do many patients not receive the recommended tests, but Dr Islam also reveals that at the final evaluation, the investigators were “disappointed to see that the testing rates actually decreased over time, with only 28% of all patients receiving fluorescence in situ hybridization (FISH) testing, 11% and 12% receiving TP53 mutational testing and IGHV mutational testing, respectively.”  

She also explores how genomic testing utilization is impacting treatment selection, noting that the use of targeted agents is increasing over time, especially in the relapsed/refractory patient population, but “a minority of patients continue to receive chemoimmunotherapy in high-risk disease.” 

Applying genomic testing in treatment selection

 

In Module 3: The why and the how of genomic testing in CLL – Discussion session 1, Dr Eyre and Dr Islam are joined by Matthew Davids, MD, MMSc, of the Dana-Farber Cancer Institute, Boston, MA, and Lydia Scarfò, MD, of the Università Vita-Salute San Raffaele, Milan, Italy, to discuss how they consider genomic features of CLL alongside the patients’ history to select optimal treatments. 

Lydia Scarfo

Lydia Scarfò, MD
Università Vita-Salute San Raffaele

 

“This is a pretty typical CLL patient,” comments Dr Davids on the case of a 74-year old female with TP53 aberrant and IGHV-UM disease. “This is clearly a high-risk patient, and I think for a patient like this, one of the most important messages is to not use chemoimmunotherapy again, and so really we’re looking at novel agent-based approaches.” 

Matthew Davids

Matthew Davids, MD, MMSc
Dana-Farber Cancer Institute 

 

Through the case studies, our expert panel highlights both the latest clinical data and areas in which further investigation is required, as well as how they approach counselling patients on treatment decisions. 

Want to learn more about the importance of genomic testing in treatment selection for patients with CLL? Explore our related free-access educational activities: 

 

 

Written by Hannah Balfour

This course is supported by medical educational support from Janssen Pharmaceuticals (a Johnson & Johnson Company) and AstraZeneca. The supporter has no influence over the production of the content.