Are Genetic Tests Recommended at Initial CLL Diagnosis?

Published on

Topics include: What Is Chronic Lymphocytic Leukemia?

Where does genetic testing fit in with chronic lymphocytic leukemia (CLL) care? Can patients acquire genetic mutations after treatment? CLL expert Dr. William Wierda, from The University of Texas MD Anderson Cancer Center,gives an expert perspective on recommended testing to evaluate prognostic factors and the optimal timing and frequency. Dr. Wierda also explains how genetic test results offer insight to the clinical characteristics of CLL and help identify high-risk disease features. Watch now to learn more.

Provided by CLL Global Research Foundation, which received support from AbbVie Inc., Gilead Sciences and TG Therapeutics.

View more programs featuring and

Produced in association with


Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Andrew Schorr:                     

Dr. Wierda, so is the question about—I guess you’d call it serial testing. So, we talked about the workup somebody might have to know what are you dealing with at the beginning, but when is it important to do any of these tests either for care or even for research down the road? 

Dr. Wierda:                 

So, I think there’s a couple of comments that I probably should make before I comment on that. And that is, these prognostic factors are not required when somebody is initially diagnosed. For some individuals, they may even heighten their anxiety that is not necessary. Not all of them always behave like we’ve been talking about. For example, if you do FISH when somebody’s initially diagnosed, and you notice that a patient has 17p deletion, not all of the 17p—patients with 17p deletion will have disease that’s aggressive. 

In fact, early on, when we were first doing FISH analysis, we noted that if in patients who are untreated, who came to our institution, about a third of them – a third of them who had a 17p deletion did not progress, and did not need treatment. And so, you can observe those patients with 17p deletion. If they don’t have an indication for treatment: they don’t have symptoms, they don’t have anemia; you monitor them, and you watch them. And you watch them closely, but a third of them won’t necessarily need treatment. 

And you do a disservice, I think, by treating them too early. And you should not treat them with chemotherapy or chemo immunotherapy, as was already mentioned. So, not all 17p deleted patients act with aggressive disease. There is some heterogeneity in terms of the clinical characteristics within the categories. And we’ve done a lot of work with prognostic factor modeling and trying to use multiple prognostic factors to get a better sense and estimate of the aggressiveness of disease. And it’s challenging, and it doesn’t give you a full picture. It gives you some idea, but it’s—you have to take it in context. 

And so, as I mentioned, you don’t need to do the testing initially, you definitely need to make a diagnosis, so CLL, which is done by flow cytometry. You don’t necessarily have to have the prognostic factors checked. We do it routinely here because I think it’s informative, and I want to know, and I know what to do with that information. And I don’t act on it unless a patient has an indication for treatment. 

The immunoglobulin V gene mutation analysis doesn’t change through the course of the disease. So, that’s something that we think of as a fixed feature. So, if a patient starts out as having an unmutated V gene, they’re going to keep that unmutated V gene through the course of their disease. Similarly, if they’re unmutated—if they’re mutated or unmutated, they stay as they were initially identified. So, you don’t need to recheck mutation status. Through the course of the disease, and particularly in patients who’ve had treatment, you can acquire gene mutations other than immunoglobulin genes. 

So, for example, you can acquire mutations in TP53, or in ATM, or any of the other various genes that we sequence. You can also acquire the larger chromosome abnormalities that we identify with FISH. So, for example, you can acquire the 17p deletion, or you can acquire an 11q deletion through the course of your disease. Typically, we don’t see acquisition of high-risk features in the absence of treatment. So, usually, patients will have the same prognostic profile when they’re initially evaluated here, at Anderson, as they have when they start on their first therapy. 

But what we do see, is the acquisition of high-risk features, particularly after treatment, and it’s more common among patients who’ve had chemo immunotherapy base treatment in terms of acquiring the high-risk features. So, patients should be retested for FISH, and a gene sequencing profile, particularly TP53, if their disease relapses and progresses, or if they develop resistance to a therapy like ibrutinib. 

The other tests that we’re doing, particularly for patients who are developing resistance to BTK-based therapies; so ibrutinib (Imbruvica) and acalabrutinib (Calquence) is mutation analysis in BTK, and PLC Gamma 2. And those two genes, we sequence, and have been associated with resistance, particularly to the BTK inhibitor-base therapy. 

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Related Programs

What Genetic Mutations Are Doctors Looking for in CLL Patients?

Which genetic mutations are important in CLL patients? Watch as CLL experts Dr. Jennifer Brown and Dr. William Wierda explain molecular testing and how some mutations affect the treatment path.


Watch and Wait: Why Isn’t My Cancer Being Treated Right Away?

Renowned CLL expert Dr. Susan Leclair helps patients understand the purpose of the watch-and-wait strategy, cancer cell behavior and signs that the condition is becoming more aggressive.


Finding the Right CLL Treatment Approach for Me

What is the right CLL treatment approach? Watch as CLL experts Dr. Jonathan Cohen and Dr. Kerry Rogers discuss CLL treatment classes and lifestyle factors to consider.


Join Our Community Register for Events Read Our Latest Blog

Page last updated on September 9, 2019