Skip to Navigation Skip to Search Skip to Content
Search All Centers

Getting the Right Genetic Testing at the Right Time

Read Transcript Download/Print Transcript

Published on February 2, 2017

What genetic tests should CLL patients have and how often?  Patient Power founder, Andrew Schorr, hosts a roundtable discussion with leading experts, Dr. Jeff Sharman, Dr. George Follows and Dr. Philip Thompson. Learn more about the importance of genetic testing, the types currently available and appropriate timing for testing.

Supported through grants from AbbVie and Genentech.

Featuring

Sponsors

Patient Empowerment Network

You might also like

Transcript | Getting the Right Genetic Testing at the Right Time

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.

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:

Let’s talk about this for a second. We talked about testing, and we talked about these drugs that deal with this more aggressive CLL, this so-called 17p deletion. But yet, I understand that labs vary in how they assess whether you have 17p or how much. And in the communities sometimes, the doctors are not so attuned to it; it varies. They have a lot of different cancers to treat. So, Jeff, do you have any guidance for patients on how their CLL can be analyzed correctly? And maybe if they didn’t do well on a treatment earlier and now they need to be retreated, should they be tested again and their 17p be looked at so that they get the benefit of a drug that may be focused on that? 

Dr. Sharman:       

We talked about IGHV mutation analysis.

Once that’s been tested, that should be stable for the entire duration of somebody’s disease. That’s not a variable that changes. In contrast, and in sharp contrast, FISH evolves. So what you are when you’re first treated is not necessarily what you are at relapse or subsequent relapse. 

Andrew Schorr:

The genetic aberrations.

Dr. Sharman:       

The genetics change. So CLL, I like to think of a patient’s course—over the course of CLL as survival of the fittest. When you treat somebody with chemotherapy, you might eradicate 99.99 percent of the disease, but that .01 percent may be what survives. And it wouldn't, therefore, surprise us that things such as 17p, which are actually quite infrequent in the front-line setting, constituting about 5 to 7 percent of patients, enriches with subsequent lines of therapy. So that when patients are on their third-, fourth-line therapy, that frequency is muchhigher; say around 30, 35 40 percent.

Furthermore, there is a gene on the short arm of chromosome 17, so the chromosome, the long arm is the Q, the short arm is the P: and there’s a gene that lives on 17p called TP53. That can be mutated, and that’s not tested by FISH, either. This is where these next-generation things—and having a TP53 mutation is every bit as bad as having FISH. All that’s to say you cannot know your FISH unless it’s retested. I think that we have data from community settings to say that about half of patients are getting FISH before their first-line therapy, and which each successive line that decreases such that when patients are on third-line therapy, FISH is done in about a third of patients.

So it’s not being done frequently enough, and here’s why it’s dangerous. Treating somebody with 17p with chemotherapy is harmful.

Dr. Thompson:

Agreed.

Dr. Sharman:       

I will go so far as to say that amongst the alternative therapies, you are making a wrong choice, and we don’t say that that often in cancer. We like to say that’s okay. No, this is a wrong choice to treat 17p with chemotherapy, because you’re taking a disease that is genetically unstable and potentially destabilizing it further with therapy that rarely yields benefit for much time at all. You’re getting all the side effects with little of the benefit. Treating 17p with chemotherapy is wrong.

Andrew Schorr:

Let me see if I’ve got this right. Let’s say I had been treated with FCR or Brett, like that. And now my disease comes back. So I’ve been through the chemo approach one time.

You’re saying that before, they’d just say well, you didn’t have long remission, but let’s just do it again. That would be wrong. I should have an analysis to see has this survival of the fittest, the 17p and p53 and all of that grown up where maybe there’s some other direction we should go. Is that correct?

Dr. Sharman:       

I think to treat 17p with chemotherapy is wrong. And those patients should go on either ibrutinib (Imbruvica) or idelalisib (Zydelig), rituximab (Rituxan) or venetoclax (Venclexta). Those are all agents available in that setting, and you may pick one regimen over another, depending upon side effects or treatment availability or so forth.

Andrew Schorr:

So, George, are we saying then that the patient and the doctor should work together to make sure they have a clear picture of their situation at the outset. 

And then if after that initial treatment or depending upon if they’re 17p at the beginning, but if they’re not, as most people are not, they have their initial treatment, and the cancer shows up again. They need to work together to have a close analysis before they do the next treatment. 

Dr. Follows:        

I echo Jeff’s views completely. I was a little disappointed with our UK dataset that about a quarter of our patients got no FISH data back on them. I think because FISH is a relatively straightforward test at the laboratory level, I think perhaps I deluded myself that every patient was getting FISH testing, particularly in the relapsed-refractory setting. That’s gold standard number one. I think also the sequencing of TP53, the commonly mutated axons, the parts of the gene when they go wrong, they matter. So that really has to get rolled out as a mainstream investigative test. And so certainly that’s what we in the UK are now pushing at every line of therapy change. 

Because I think it is important, particularly if you’ve had a longremission with immuno-chemotherapy, it’s still not absolutely clear that if you are a wild type of 17p, so you don’t have the mutation, that it might fit with you to have another short burst of immuno-chemo to push yourself into remission for another two, three years maybe and then start newer drugs. I think perhaps touching on some of the longer term follow-up from a higher state, and then Susan O’Brien’s data, which was very similar to our UK data, that actually two or three prior lines of therapy, if you start your ibrutinib, you seem to do as well as one prior line of therapy—of course, again, retrospectively looking at data. 

But, actually, I think that means that we do have these choices; they are potentially available to patients and worth discussing. But within the context of checking it, because I completely agree with Jeff. 

Andrew Schorr:

Get a clearer picture of what's going on.

Dr. Follows:        

It’s a mistake to treat the patient with chemo if they have 17p.

Andrew Schorr:

And have a picture now, whether it’s at the outset for sure, but again along the way; get a clear picture of what you’re dealing with.

The patient needs to advocate for that. 

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. 

You might also like