Ask the CLL Expert Live Replay

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Topics include: Treatments and Understanding

Leading chronic lymphocytic leukemia (CLL) expert Dr. Jeff Sharman, from the Willamette Valley Cancer Institute and Research Center and The US Oncology Network, joined Patient Power to answer your questions LIVE. Watch the replay of this 30-minute session now to hear a CLL specialist’s perspective on answers to questions about treatment, research, managing side effects and more. 

This is a Patient Empowerment Network program produced by Patient Power. We thank AbbVie, Inc. and Pharmacyclics for their support.

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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:

Greetings to this live Ask the Expert program for those of us dealing with CLL.  I'm Andrew Schorr from Patient Power.  Welcome to this Patient Empowerment Network program with financial support from AbbVie and Pharmacyclics.  Thank you so much for being with us.  

We have a wonderful expert with us today who is so knowledgeable about this, and that is Dr. Jeff Sharman.  Dr. Sharman is the medical oncologist, of course, one of them at the Willamette Valley Cancer Institute and Research Center in Oregon. He's also the medical director for hematology research at the US Oncology Network with oncologists all across the country.  Jeff, welcome back to our program.  

Dr. Sharman:
Thank you so much.  It's nice to be here today.  

Andrew Schorr:
Okay. Let's get started.  We have a lot of questions coming in, and if you, our viewer, have an additional question send it to cll@patientpower.info and we'll cover as much as we can in the next half-hour.  

Here's a question that came in based on news events that people follow related to CLL, and this is from William.  He says, I heard there's a new drug approved for CLL, duvelisib (Copiktra).  Can you tell more about this?  Where does it fit in in the CLL landscape?  

Dr. Sharman:
Absolutely.  Duvelisib is another PI3 inhibitor.  It has considerable molecular similarity to idelalisib, which was the first in class medication approved amongst the PI3 inhibitors a few years ago.  This molecule has considerable both biochemical similarity, structural similarity but also quite a bit of clinical similarity. So when you look at the patient population in which it's approved, similar clinical trial designs led to approval, and so as a result it's sort of in the third?line setting that you could use it.  

It is a—the drug class is a sort of the whole PI3 family of which there's a growing number.  There's idelalisib (Zydelig), umbralisib is in late?stage clinical trials. Copanlisib (Aliqopa) is approved in follicular lymphoma but not CLL.  And as a family they tend to be utilized less frequently than the BTK inhibitors such as ibrutinib (Imbruvica) and to some degree less frequently than venetoclax (Venclexta), as well, the Bcl?2 family, and that has to do with some of the side effects, that there is, a frequency of diarrhea, LFT abnormalities and so forth.  So it follows on the heels of idelalisib, and I would say has more similarities than differences.  

Andrew Schorr:
Okay. Let's go on.  You mention about side effects.  People ask about that all the time, so here's a question from Judy. She says, I'm not able to get an answer from my husband's oncologist regarding ibrutinib and severe body cramping. Have there been any reports showing this is a possible side effect from ibrutinib?  

Dr. Sharman:
Absolutely, it is.  It is—well, absolutely possible, let's say that.  It actually is what I would say one of the most common side effects that I encounter as a limitation for ibrutinib.  The medical term for it is arthralgias, which is sort of translates into joint pains. Sometimes you'll also see actual cramps or spasms.  I've had patients' hands lock up when they're driving sometimes, which can be a little bit concerning.  

There is I think considerable question in the field. There are differences amongst thought leaders on this as to whether—how to best manage it.  

There are some studies that suggest that lower dosages may—after a patient has been on ibrutinib for a length of time, you may be able to get away with lower dosages.  Those pieces of clinical trial data are not as large and not as well validated, so I think it's still in the hypothesis?generating mode, but there's some data that suggest you could do it.  And if the choice was lower dose of ibrutinib or no dose of ibrutinib, I would probably go with a lower dose.  

The other potential solution now is acalabrutinib (Calquence), which is a second BTK inhibitor approved.  It is approved by the FDA for mantle cell lymphoma.  However, a lot of the clinical trials are in chronic lymphocytic leukemia, and there have been studies that looked at patients who have limited tolerance of ibrutinib, and in many cases they were able to go on acalabrutinib without a recurrence of the same side effects.  

So that's another possibility.  It is in the NCCN guidelines that for those patients who have intolerance of ibrutinib consider acalabrutinib.  So whether it's dose reduction or drug substitution, those are sometimes two ways that I use to get around that scenario.  

Andrew Schorr:
Okay. Now, we should be clear that acalabrutinib is not yet approved for CLL.  Does it seem like that's forthcoming?  I mean, nobody can guess the FDA, but.  

Dr. Sharman:
Yeah.  So the clinical trial that will lead to approval, presumptive approval, was a head?to?head comparison against investigators' choice of bendamustine rituximab or idelalisib-rituximab (Zydelig-Rituxan), and that study is fully accrued and waiting for end points.  

And I think that the feeling would be that should be a positive test and that it would eventually get CLL approval.  Most of the studies have been done in CLL.  It's just the mantle cell indication came along more quickly.  

Andrew Schorr:
Okay.  All right.  A lot of people worry about other side effects like fatigue, of course, in CLL. So here's a question from Patty. She says, I've been taking 60 milligrams of Vyvanse, which is often used for ADHD, for extreme fatigue that she struggles with.  And she says her blood pressure is elevated, and she's read that that can be a side effect of lisdexamfetamine (Vyvanse).  Are there any new or additional medications that can be used to treat fatigue without the worry of high blood pressure?  

Dr. Sharman:
The way I would approach that situation, fatigue—what I don't know about this particular patient, is this fatigue that is attributable to the CLL or fatigue that's attributable to medications?  

CLL fatigue is probably one of the most bothersome sort of clinical realities, and for some patients even though they may not meet other treatment criteria such as rapid rise in white blood cell counts, systematic adenopathy, marrow dysfunction.  Sometimes fatigue is so debilitating that you need to do treatment for it.  In the 2008 guidelines, fatigue was one of the—it was like the sixth indication for when you treat CLL.  

And I've seen some patients, you know, one immediately jumps to my mind.  He's clinician himself, very busy individual, likes to surf and so on and so forth, but his CLL left him so fatigued that he had to cut back on clinical work and so forth. And getting his CLL under control really made a huge difference for him.  So in the setting of CLL I think that you may wish to consider talking to your doctor about going ahead and treating.  

I find those are difficult, difficult discussions because if you don't have the more classic indications for therapy, it's hard to know. Because fatigue can be a number of things.  It can be thyroid dysfunction.  It can be hormone imbalance with other hormones.  It can be nutrient deficiencies and so forth.  

Andrew Schorr:
It could be having three kids.  

Dr. Sharman:
Absolutely.  

Andrew Schorr:
Yeah, I know.  Lots of things.  

Here's another question from Bob.  Bob wants to know, will approaches likely change for first?line treatment, for instance venetoclax, or Venclexta, within the next two years?  You have ibrutinib first line.  

Dr. Sharman:
Yeah.  

Andrew Schorr:
You have FCR that's been around.  You have idelalisib I think could be used first line.  

Dr. Sharman:
Actually, idelalisib is specifically contraindicated for first?line therapy because of side effects.  

Andrew Schorr:
Okay.  So what about first?line therapies, Jeff?  Where are we there and what's coming?  

Dr. Sharman:
Yeah, so you're kind of in this bind currently where your choices are chemoimmunotherapy or targeted therapy, and both of them have strengths and weaknesses. The strength of chemoimmun0therapy is that you give treatment for a fixed duration of time, and then you get treatment?free interval that in properly selected patients should be measured in multiple years.  

Andrew Schorr:
I went 17 years.  

Dr. Sharman:
Yeah, absolutely.  So effective therapy in appropriately selected patients.  Now, when I say appropriately selected patients, that does get into some of the nuance about FISH changes and IGHV mutation, and I will tell you even amongst thought leaders in the field there's some debate as to where you draw the line.  Some patients are more suitable for ibrutinib either because of co?morbidities or wish to avoid chemotherapy, but at least as of today ibrutinib is something you start and then stay on indefinitely.  

And per the prior question, some patients have difficulties with that, whether it's arthralgias or bruising bleeding and so forth.  The medication you made mention of I think is the frontline therapy that may have the most profound impact on treatment selection in the next two years.  

Andrew Schorr:
Venetoclax.

Dr. Sharman:
So the German Research Group, which is really just absolutely one of the best out there, have fully enrolled a clinical trial of obinutuzumab-venetoclax (Gazyva-Venclexta) versus chlorambucil (Leukeran) and obinutuzumab, and I have to believe that that is going to result in a superior outcome for the venetoclax arm and that we will have the combination of obinutuzumab venetoclax for front?line setting.

And what's really appealing about that is that is one year of treatment and then treatment is suspended and stopped.  And though we haven't compared that to more traditional BR or FCR, I think it would be a highly effective regimen.  We are currently conducting a study in the United States in our research network looking at the combination of obinutuzumab and venetoclax, and what I like about our study is we give—for the listeners who might not be familiar with venetoclax, starting venetoclax is a little bit clunky because it works so quickly we have to be careful about a condition called tumor lysis syndrome, which is if you kill too much cancer cells too quickly that can cause some dangerous conditions, and venetoclax does do that.  

And so what we're doing is we're giving two months of obinutuzumab and sort of getting rid of the bulk of the CLL and then starting the venetoclax hopefully under much safer conditions because, you know, in the Pacific Northwest we would say you can't have forest fires if you don't have any trees. So if we get rid of all the CLL or a substantial fraction of it somebody is less likely to have tumor lysis.  So I think that's the approach that is probably the next up in frontline.  

The one other thing that could potentially change is acalabrutinib has conducted a three?arm study—excuse me, Acerta with acalabrutinib, where they give—it's a three?arm study with either chlorambucil-Gazyva, acalabrutinib or acalabrutinib with Gazyva.  And so does the addition of a C?20 antibody make BTK work better, remains the question outstanding.  

Andrew Schorr:
All right.  Let me just explain things to people.  I've been around this for a long time, and Jeff deals with these acronyms all the time.  So, first of all, Gazyva is the same as obinutuzumab.

Dr. Sharman:
Thank you, yes.  

Andrew Schorr:
It's an infused CD20 that's targeting the CD protein on the B?cell, the bad guy, and it is sort of I don't know if you'd describe it as a more powerful version but it followed from Rituxan or rituximab that many of us had.  So the idea is you have an infused therapy for some length of time, and then you may have an acalabrutinib with it or you may have a venetoclax or Venclexta with it. Get I get it right, Jeff?  

Dr. Sharman:
Yes.  And if I just had one other comment.  I think there are a lost questions and certainly some very compelling data about the combination of a BTK inhibitor such as ibrutinib (Imbruvica) with a Bcl?2 inhibitor such as venetoclax.  

Andrew Schorr:
Two pills.  

Dr. Sharman:
Two pills, yes.  And I think the preliminary data really looks extremely encouraging.  

The challenge with that approach is it's not approved in that combination and probably not going to be approved in the next two years unless the FDA does something that maybe I'm not anticipating at this point.  That clinical trial that compares that to an existing standard is really only just getting off the ground now.  

Andrew Schorr:
Okay.  All right.  Let's buzz through some others.  So John writes in, please compare purpose and benefit differences for FISH testing versus next generation sequencing.  So maybe you could explain them too.  

Dr. Sharman:
Absolutely.  Thank you for the question.  It's one that I think is often very difficult to comprehend.  

So a little bit of history here is that we've known for a long time with that patients with chronic lymphocytic leukemia have a pattern of common chromosome gains or losses, and we generally pay attention mostly to five separate categories.  \

There are some others that people sometimes look at, but ranging from sort of worst to best, worst is having a loss of chromosome 17p and P stands for petite arm, so part of the short arm of chromosome 17 is lost. 11q, Q stands for the long arm of chromosome 11.  And then you have normal chromosomes or the addition of an extra chromosome 12 or the loss of a portion of chromosome 13 that kind of goes from worst to best. And that is very different than actual mutations in genes.  So these are wholesale losses of large clunks of chromosomes.   

And if you look at 17p, the reason that 17p is bad is because there's a particular gene there that's very important called TP53, and you can actually have a mutation in TP53 without the presence of a chromosome loss. And so next generation sequencing looks at a host of additional genes that really until the last three to four years we didn't know have the significance that they have.  So TP53 is probably the most important, but you're also seeing things such as SF3B1, NOTCH1, FA1.  There are a variety of them that are out there.  Some are better understood than others, and I think to some degree we're still as a field even trying to figure out how best to integrate these into our clinical practice.  

Andrew Schorr:
Okay.  So would you recommend for the typical CLL patient that they have FISH testing, which tells you about the chromosomes, right?  

Dr. Sharman:
Yeah. 

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Page last updated on May 28, 2019