How Do CLL Experts Determine a Treatment Path?

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Topics include: Treatments

How do physicians determine which CLL treatment is right for a patient? Patient Power founder, Andrew Schorr, hosts a roundtable discussion with Dr. Jeff Sharman, Dr. Philip Thompson and Dr. George Follows.  Together, these experts discuss the tools, including genetic testing, used to guide a treatment path. 

Supported through grants from AbbVie and Genentech.

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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:

Our view as a patient and the patient community is hopefully everybody gets the treatment they need and deserve, recognizing their costs. And now, Phil, we’re increasingly talking about combinations. Years ago, I had FCR, and now you’re talking about ibrutinib(Imbruvica)being combined with other drugs, or venetoclax (Venclexta) being combined. How do you figure out what's right for what patient?

Dr. Thompson:  

We have increasing data now on looking at genetic factors in an individual’s CLL cells before they’re treated, which can give us a good idea as to who is going to—more than just what their prognosis is, will they do better on one specific type of therapy, which is very useful early on. At MD Anderson now, when we have a patient who is about to have their first treatment for CLL, we get a number of tests done. We get FISH to look at the chromosomes in the cells. We get what's called IGHV mutation status testing, and we also do a panel of what we call next-generation sequencing, which looks for small mutations in genes. And based on those three tests, we can get a good idea of how well is someone going to respond to chemotherapy.

And if they fall into a group of patients that’s likely to do well on chemotherapy and they’re young and fit, then we tend to go for that type of treatment. But for the remainder of the patients, we now have a combination study of ibrutinib and venetoclax, so we’re kind of dichotomizing treatment, in a sense based on those predictive markers. 

Dr. Sharman:       

Andrew, I think this is an important area and one that is underappreciated by a lot of practicing clinicians. The paradigm until recently was primarily about looking at the patient, not necessarily the disease. The patient was a combination of age and functional status, and the idea was treat as intensively as you can. And I think that the paradigm is changing.

And central to that paradigm change are some of these molecular characteristics. In particular, Philip’s group has looked at the long-term outcome for patients with FCR, and there’s a clear delineation amongst those patients who have IGHV-mutated versus unmutated disease. This is a situation where having the mutated version is actually good. So with FCR, I don’t know if there’s a completely representative population in that study; 57 years old was the typical age.

But there are patients out 14 years, 15 years without their disease coming back. You would not get that sort of result out of somebody who is IgVH unmutated. And so really I think central in that paradigm right now is the IgVH mutation status, and then following that are these additional tests: the FISH and the mutation tests.

Andrew Schorr:

So let me ask you a question about that.

You represent really community oncologists throughout the country. You are one of the leads. And so somebody goes to MD Anderson, and he runs all these tests. It’s a big university center, I don’t know to what extent you do that. 

Dr. Follows:        

I think we run even more, Andrew.

Andrew Schorr:

Okay. But all these tests—if somebody says gee, doctor in whatever state I’m in or whatever community, I need all the—a broad range of tests. Maybe, but maybe not. So maybe you could help our viewers understand from your view. Where do these come in 

Dr. Sharman:       

First of all, I think that the IgVH mutation analysis is poorly understood by most practicing providers. I think there is a significant misunderstanding and even amongst physicians I know firsthand who are interested in hematology, there’s oftentimes a lack of total awareness of what this means. To me, IGHV mutation analysis defines treatment intent. 

So if my treatment intent is short-duration therapy with sustained benefit, that’s a patient where I’m going to treat as intensively as age and functional status will allow me to. So those patients who have IGHV-mutated disease, particularly if they have good FISH and none of the mutations, that’s a patient where I would still reach for FCR in a younger patient or in somebody who’s maybe, say, above age 65 but wants short-duration therapy. I think that’s a patient who is still suitable for perhaps a bendamustine-based (Treanda) approach.

Whereas if the treatment intent is just disease control as long as possible, continuous oral therapy may be the way to go, and Imbruvica in IGHV unmutated, or somebody who’s mutated with some of the adverse FISH findings such as 17p ornext-generation TP53 mutation.

The tests, they’re expensive but relative to the therapies, they’re actually quite inexpensive. And so I think it’s money well spent to appropriately characterize the treatment intent for which you’re approaching a patient. 

Dr. Follows:        

Then I would follow that on and say our job as physicians really is to translate this complexity for our patients to give them a feel for balance of risk. Because I think that’s what all of these mutational tests, whether it’s a targeted mutation of a particular oncogene or sequencing of urine globulin protein, immunoglobulin sequence, it’s giving us this big feel of how we think that patient will do. Now, of course the toxicity, the short-term toxicity of FCR is going to be the same whether you’re mutated or unmutated. But if you’re saying to a patient look, I’m aware you’ve got some comorbidities and your 60, 62 but you’re13q deleted, you’re mutated; we think you can do really well.

So actually, taking that up-front risk is worth doing. But if you’re saying you’re a mutated compared with BR, this is going to push out your remission, well, an extra maybe 12, 14 months or so. But we’ve got so many other things down the line. Is it worth taking that risk? So I think for me, that’s what the molecular allows us to do with our patients.

Andrew Schorr:

And people need to have that discussion with their doctor. But based on the test results, so you get that picture. 

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 June 21, 2017