Identifying CLL Patient Subsets: What Does Mutational Status Reveal About Disease Risk?

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What does mutational status mean for chronic lymphocytic leukemia (CLL) patients? Which genetic mutations are considered high risk? Renowned CLL expert Dr. Jennifer Brown, from Dana-Farber Cancer Institute, explains what genetic mutations are significant in CLL patients, which have prognostic indications, and how mutational status can influence treatment decisions and response. Patient advocate Michele Nadeem-Baker also shares why it’s important for those living with CLL to learn about genetic mutations. Watch now to learn more.

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

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Transcript

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. Brown, back to you. So, you took us through these different parts of genes, you know, 11, and 13, Trisomy. So, help us understand, again, if one of us is sitting in front of you, help us understand the choices. TP53 significant, and that’s tied in with this 17p deletion. Right? 

Dr. Brown:                  

That’s right. 

Andrew Schorr:          

So, we get it, that that’s a concern, but what about the others? Are they all the same? Are they different? As far as significance goes.  

Dr. Brown:                  

Right. Well, they’re all somewhat different. 11q deletion has historically been associated with higher risk in the setting of chemo immunotherapy, shorter time to therapy as well as relatively poor response, shorter response time. So far, we’re still evaluating the effect of 11q deletion in the setting of novel agents. But with Ibrutinib in the clinical trial, so far, it appears that the patients with 11q deletion are doing as well on ibrutinib (Imbruvica) as the patients without 11q deletion in the patients who’ve had fewer prior therapies, those who are frontline, or first or second-line. 

In patients who had more like four prior therapies, we do see a somewhat shorter response duration with 11q deletion. But so, it appears that the novel agents may mitigate the historically worse effect of 11q deletion. And so, with Trisomy 12 and 13q deletion, they can be quite variable. And what I usually tell patients is that with those two, I look a lot at another test, the IGHV mutational status when I think about how the disease is likely to behave. 

Because, trisomy 12 can be associated with relatively more aggressive behavior, but it can also be associated with slower moving behavior. And to some extent, that depends on whether or not, how it’s associated with the IGHV test. And similarly, with 13q deletion. 

So, the IGHV test, we know, divides people with CLL roughly half and half between two groups. One group, that has much slower-moving disease toward treatment, and which has historically very good responses, potentially even curative responses with chemo immunotherapy with FCR, that’s the mutated IGHV. And the other group, the unmutated, as a shorter time to treatment, and historically, not as durable responses with chemo immunotherapy. 

But again, in the setting of ibrutinib, we’re seeing that in patients who are getting ibrutinib frontline or second-line, that responses appear to be as durable with the unmutated as the mutated type. 

Andrew Schorr:          

And Michelle, I think you found out that you were unmutated in your?

Michele Nadeem-Baker:        

Correct, 11q deletion, and unmutated IGHV.

Andrew Schorr:          

But you had the FCR, but then, as Dr. Brown was just saying, you’ve had the ibrutinib, which seems to be effective, even in the unmutated.

Michele Nadeem-Baker:        

Correct, and frontline treatment for me. Frontline treatment setting, as Dr. Brown was speaking of. 

Andrew Schorr:          

A question for you, from the patient perspective, as you listen to this, and this has been discussed with you over the years, is it unnerving? I mean, look, we come to CLL, we’ve never heard of any of this. And then, you start hearing about mutated, unmutated, 11, 13 Trisomy, 17p—it’s a whole other language. Have you made peace with all this stuff? 

Michele Nadeem-Baker:        

Somewhat. Somewhat. Of course, it’d be great to hear that I’m cured, someday, that would be wonderful. I’m hoping that will happen. But I have. And it’s you really have to become educated in that. I feel like I have – you know, I drank from a fire hose in the beginning, and there continues to be all sorts of new information due to the advancing research out there. So, you have to stay on top of it. That’s one thing I would tell patients. 

But the more you learn, and as Dr. Brown can attest, I always want to know everything, and I ask a million questions—probably, my journalism background. But I find for me, anyway, it’s better to – and not everyone’s like this—but for me, it’s better to know. And the more I learn, the more at peace I can become because I understand CLL better, and how what I’m on is basically keeping it in check at this point. And for everyone out there, that’s my suggestion, is that you really do learn all these things. 

And yes, in the beginning, I just remember looking at this list from a test, and not understanding a thing, what all this meant, what was this series of numbers and letters I’ll put together; it was alphabet soup. And then, when I started learning more about it, I realized what it meant, but what it also meant for me. Not only for other patients, but there’s so many different variations of CLL. 

So, for me, in the beginning, I honestly did not know what unmutated and mutated meant. I thought unmutated—wrongly, I thought it meant a better thing because it meant it hadn’t mutated. And then, I soon learned that that was not necessarily so.

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.

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Page last updated on March 28, 2019