Replay: Ask the CLL Expert Live

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Topics include: Treatments

CLL expert Dr. Nicole Lamanna joined us at the American Society of Clinical Oncology (ASCO) meeting in Chicago to answer audience questions live. Watch the replay to hear Dr. Lamanna’s expert answers and her perspective on developing research announced at the conference.

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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. 

Carol Preston:

Hello everyone and welcome to Patient Power.  I'm Carol Preston, and we are at ASCO, the American Society of Clinical Oncology, and this is our Ask the Expert live segment.  Focus today is on CLL, chronic lymphocytic leukemia, a disease that I've been living with for nearly nine years now, and our specialist is Dr. Nicole Lamanna from Columbia Medical Center. 

Dr. Lamanna, first of all, thank you so much for being here with us. And before we go to questions could you give us a quick recap of the CLL news out of ASCO?  

Dr. Lamanna:

Sure.  I think the biggest news out of ASCO was the combination of chemoimmunotherapy with ibrutinib (IMBRUVICA®) in patients who had prior treatment for their CLL.  This was presented by Asher Chanan-Khan, and this was probably a land-breaking report because it was sort of the—one of a very large Phase III study looking at patients having either bendamustine/rituximab plus ibrutinib or receiving bendamustine/rituximab (TREANDA®/Rituxan®) plus placebo.  And clearly the results were very favorably overwhelmingly in support of the combination of ibrutinib with bendamustine and rituximab, both from responses but not—not just responses but also for progression?free survival, a reduction of death, risk of death. 

And so I think that this is probably one of the many that you will see in the future of showing that the small novel kinase inhibitors along with chemoimmunotherapy programs are going to be one strategy to take for patients whether—in this setting it was patients who had prior treatment, but certainly I think you're going to see lots of studies showing this in the upfront setting, patients who have never had prior treatment.  So there's a lot going on right now.  

Carol Preston:

Very, very encouraging news and a lot of hope for patients who have CLL.  All right.  Before we get—start taking questions, a few housekeeping matters to take care of.  First of all, our live Q&A is sponsored by the Patient Empowerment Network, PEN, through an educational grant through AbbVie, and we thank them both. 

The views expressed that you're going to hear today are not necessarily the views of Patient Power, PEN, the program sponsors and the partners. 

This discussion, and this is so important, is not a substitute for your seeking medical advice for your specific situation from your doc, from your medical team.  And when you ask your questions, and you'll do that via the QA button on your Zoom window, please, the questions shouldn't be specific to your situation. 

So with that, Dr. Lamanna, let us get started.  And our first question is from Julia, who asks when the new targeted inhibitors like ibrutinib and idelalisib (Zydelig®) will be approved for frontline patients, not just relapsed or refractory.  

Dr. Lamanna:

Ibrutinib is currently also approved frontline—just for those who don't know—is approved frontline for patients with a 17p deletion.  But, absolutely, there are several studies that have either closed or are finishing accrual now that have combined or looked at these agents in the frontline setting so in patients who have not had any prior treatment.  And so I think you're going to see that these drugs will probably get approved fairly soon, of course, we're hoping within the next year or two.  But obviously that's very dependent on some of the data and the FDA of course, but I think—I would be surprised if these drugs did not get approved in frontline as well. 

Carol Preston:

All right.  Excellent.  And Melissa asks what is the status of ABT-199?  She had heard that it was approved. 

Dr. Lamanna:

Yeah, so ABT-199 is a Bcl-2 inhibitor.  It is not yet approved for CLL, but this was also a drug that has many clinical trial data behind it in support of it, and there is no doubt that we also anticipate that that drug will be approved as well.  Of course, it may not be approved initially in a frontline therapy, likely in patients who have had prior treatment for their CLL, and I think there'll be some data that is going to be forthcoming soon regarding ABT 199.  And so I think that will also—I think we should probably see approval probably next year, as well.  

Carol Preston:

Wow.  So the CLL treatment options are exploding. 

Dr. Lamanna:

Are going to be—yeah. 

Carol Preston:

I do want to remind our online audience how to ask a question.  Just click the Q&A button on your Zoom screen.  We are ready and waiting for your questions so that we can pass them along to Dr. Lamanna. 

You know, I read just in the last couple of days about viral treatments, the herpes viral—virus in fact, for solid tumor treatment.  Is viral treatment—and we actually have a question from Ron similar to that, are viral treatments being considered? 

Dr. Lamanna:

Yeah.  You know, obviously there's been a lot of interesting clinical trials and interesting laboratory data looking at pairing certain therapies with viral vectors as a target for cancers in general. And certainly this isn't necessarily new, but I think that improvement in technology and improvement in our ability to deliver some of these ideas that were probably generated actually decades ago is now becoming more of a reality. 

So I think you will probably see some of this both in not only the solid tumor sector but of course in the hemalogic malignancy sector, and I don't think CLL will be immune to that.  So I think you will probably see different types of immunotherapy being looked at in CLL as well.  

Carol Preston:

All right.  So we have a question from Layda or Layda, and I hope I've pronounced that correctly.  Can you develop Richter's syndrome at any stage of CLL?  Can you develop Richter's when disease progression is slow, or does it appear only in a more advanced and aggressive CLL? 

Dr. Lamanna:

I think that's a great question.  Most of the development of Richter's transformation is in patients who have had prior exposure to chemoimmunotherapy, so the predominance, even though it is in general not a common occurrence, it can happen—depending upon the literature that you read, anywhere from 5 to 15 percent of patients with CLL can develop Richter's transformation.  But certainly it's more seen in patients who have had some prior therapy.  So can you have it if you're being monitored, and it seems like your disease course is very indolent—I hate to use the word "indolent" because slow growing…

Carol Preston:

Slow growing, yeah. 

Dr. Lamanna:

…because you know we don't consider this benign by any means, but for somebody being watched can they develop it?  Yes, they can.  It's just not as common.  The majority of folks are really patients who have had prior chemotherapy. 

Carol Preston:

Yeah.  And just to follow up and to clarify the signs and symptoms of Richter's. 

Dr. Lamanna:

Sure.  Most patients with Richter's, generally they notice that something's wrong.  They're presenting with more fatigue than they usually did.  They may develop a lymph node that grows out of proportion to what they are—you know, what their body is normally doing with regards to their CLL. 

Patients who have lymph nodes with their CLL as the disease slowly progresses may have slow growth, but if something really pops up and is, you know, uncomfortable, firm, they're having fatigue, weight loss, night sweats, they just don't feel good, oftentimes—sometimes this could be concurrent to an infection that's going on, and sometimes we'll try and treat an infection and see if that is what may be triggering this, but other times there's no doubt this is—the patient with Richter's feel differently.  They'll go back to their doctor and say, something is just not right.  I don't feel good. 

And this is one where then we start evaluating and looking for something else.  We'll do a CT PET scan, or we're trying to figure out why they don't feel good.  It's not the same as what their pattern of their CLL had been. 

Carol Preston:

So patients who develop Richter's, it's very, very scary.  

Dr. Lamanna:

Yes. 

Carol Preston:

Because the prognosis in the book, in the literature anyway says 12 to 18 months.  However, I'm reading that more and more patients with Richter's are living longer and longer.  

Dr. Lamanna:

Yeah. 

Carol Preston:

So just one more quick follow?up on that, what's transforming with Richter's that it's taking some of the scare out?  

Dr. Lamanna:

Yeah, well, and part of it I think will be exposure to some of these new agents.  So we don't know the tempo.  Will the—will Richter's behave differently in the era of some of these new agents that we're utilizing?  Will that make thinks different or even affect how the course is for those individuals?  I think that's one answer we don't know. 

I think there's a lot of different therapies now that are available that we didn't have before.  Traditionally—and we still do, it's because—believe me, I still think there's a lack of therapy for those folks.  You know, traditionally we use more lymphoma?base therapies, but there's a dire need for other therapies for patients with Richter's, and I think with some of these new agents there's no doubt—and there are actually now hopefully some clinical trials that would actually specifically address patients with Richter's transformation.  So we're hoping to look at newer agents for these folks, and hopefully we can better this part of the disease. 

Carol Preston:

Yeah, encouraging news.  I want to follow up to your recap of the news from ASCO, and this is from Gina, who says her first treatment was with FCR.  I know FCR very, very well.  She just completed BR, which is bendamustine/rituximab and wants to know if she would be eligible for this new combo therapy of BR plus ibrutinib if she relapses. 

Dr. Lamanna:

Sure.  You know, I think—and, again, this is very important.  I know, Carol, you said this earlier.  I think it's important.  You need to discuss this with your physician, of course. But I think for somebody who has had a regimen recently such as bendamustine and rituximab if you need to have therapy again—I would advocate first that obviously if you're fine not to have any therapy—but certainly if you need therapy again, it depends on the time difference between when you need to start another therapy again. 

If it's a great distance, you know, from that—your last therapy to a new therapy can you receive something you've received?  You could.  If it's a very short time period, you might not want to receive bendamustine and rituximab again even if it's with a new agent just because you just received it.  So in the short term—not to say you wouldn't have maybe an additional synergy or a benefit, but there [are] lots of opportunities for all these new agents, so it doesn't mean that you necessarily have to go back to the chemoimmunotherapy program you've just received.  

Carol Preston:

Yeah, and again, just to remind Gina and everybody else who has joined us online, please, please, please, these are important conversations with your CLL doc

Dr. Lamanna:

Absolutely.  

Carol Preston:

Yeah, specialist.  All right.  From Julia, what is the status of—we were just talking about this earlier—the CAR T clinical trials using ROR1 as a target? 

Dr. Lamanna:

Yeah, sure.  Sure, sure.  I mean, I'm just going to make some general comments about the CARs in general.  Obviously, this is a very…

Carol Preston:

Yeah, and if you could define what they are first… 

Dr. Lamanna:

Sure.  

Carol Preston:

…for some people who are new to this. 

Dr. Lamanna:

Yeah, sure.  So this is a very novel type of a therapy looking at chimeric antigen receptors against your CLL cells. So essentially it's sort of—for those of you who don't know the process of this, actually it's taking a sample of your blood, modifying it with a viral vector, modifying it to recognize one of the proteins on your CLL cells, and then infusing that back into you. And it's sort of in a way tricking your immune system to attack your CLL cells. 

Now, traditionally when we've done some of these initial studies with CAR therapies you do get some chemo, you do receive some chemotherapy with the infusion.  So it's not chemo free.  I just like to specify that because I think when—I think the physicians, sometimes we don't do a great job of saying what's involved with all of these unique therapies, so people think, oh, it's a great—it's not chemo.  No, it's still chemotherapy. 

So it's a pairing of your sort of immune system to attack your CLL with a little bit of chemotherapy as well.  There's obviously a lot of data about how it's really helped many folks with CLL, not only CLL but actually acute lymphoblastic leukemia as well.  But this is definitely specialized therapy.  There is going to be a continuation of all of these trials, whether it be in leukemias as well as actually now solid tumors.  And so I think that using again this whole immunotherapy program, sort of utilizing your immune system to see if it can attack your cancer cells, you're going to hear this over and over and over again, whether it be with CARs or some of those other oral immunotherapies, this is going to be a mainstay in cancer care.  So there are trials running specifically with ROR1 and others, and I think you'll see more and more data about this. 

Carol Preston:

Yeah, and we'll certainly look forward to the big hematology meeting in December for that.  From Mark, it's a good question, what is the long?term impact of taking ibrutinib?  You know, what do you know at this point?  It's only been on the market for what, a year? 

Dr. Lamanna:

Yeah.  Technically.  So technically it's been on the market a year. However, we do have some encouraging updated data.  John Byrd and colleagues actually republished what their long?term—long?term, you're right, being only three or four years—but their long?term from their initial ibrutinib studies, both in patients who were treatment naive, meaning haven't had therapy, and patients who had prior therapy as well, and they looked at the long?term outcome so far.  And it's very, very encouraging. 

But, yes, I'll admit to everyone that it is a little premature and naive, but it's really showing that patients who are on ibrutinib who are doing well, actually you can even see the longer somebody is on ibrutinib their responses actually can continue to improve, that they can achieve complete remissions.  It may not be year one, it could be—the median time could be year two.  They're seeing patients to achieve a CR at year three. 

So, believe it or not, these drugs may not have the same—you know, when we compare purely the kinases to chemoimmunotherapy or IV stuff, you know, we're seeing that that's stuff obviously is a lot harsher and a lot quicker, but we're seeing these responses that continue to evolve on the oral therapies that are very encouraging and less toxic.  So the updated three?year data is really, actually showing very, very well. 

So it's I know only three or four years but stay tuned.  And, yes, we're all going to be interested in looking at what that means and what the long?term side effects of some of these oral agents are, but still right now it's still very encouraging. 

Carol Preston:

Yeah, that's really, really good news.  Anonymous—person didn't want to use the name—what is the prognostic significance of 11q deletion based on percentage of cells with the deletion?  And I do understand that.  I have 17p, but I know that only 4 percent of my cells are 17p, so the specialists say take a breath. 

Dr. Lamanna:

Right.  I think so there's—just to, before specifically answering that question, I think what you brought up is very important.  You may have a chromosomal abnormality that's associated with your disease, but you're right. There's even variability in what that means for an individual patient.  And individual patients can also be different, present differently, may have what they think is the most aggressive feature and be doing very, very well. 

So that being said, you have to take it into context with everything going on.  In the literature, there's no doubt that many of us have reported that the higher the percentage of those cells expressing that abnormality, that they tend to bear out.  In other words, so that if you have 50 percent of deletion of 11q that you're probably—we know that 11q is usually associated with individuals who have bulky disease, respond well to chemoimmunotherapy, but the response duration is shorter than those, let's say, with more favorable prognostic markers, such as a deletion 13q. 

And so the percentage of cells does matter, but we will argue and quibble amongst ourselves about what is the cutoff.  Is it 5, is it 10, is it 20 percent?  And so, you know, even within that small—when you get down to a smaller range there's some argument about what that means.  Obviously, if you've overexpressed it a lot, then you can take the data as it is in whole.  So we know that again patients with 11q we tend to—many of us, we tend to like to use alkylators for that disease, although now with all of oral therapies I think that sort of is bust.  I think that with the oral small molecule inhibitors you can say it doesn't—it doesn't matter now. 

Carol Preston:

For those who do have 11q or 17p, say a small percentage, is the likelihood that the percentage will increase or not necessarily?  

Dr. Lamanna:

That's a—that's a really good question.  There's no doubt that over time—and again part of this might be a clonal evolution of the disease.  I know that many of us have spoken about what that means, that there are individuals that once they're exposed to chemotherapy that certainly you can increase their percentage.  This is why we talk about—when we talk about 17p we talk about that some—that it's not a common abnormality to have in patients who are newly diagnosed with CLL.  It's about 6 to 7 percent of all the folks with CLL. 

Carol Preston:

Yes, and when I was originally diagnosed it was—there were no unmutated markers. 

Dr. Lamanna:

So it's a very uncommon abnormality to have, but as patients go through the course of the lifetime of their disease and may have had prior chemotherapy programs, that's where we see the bulk of the folks are really 30 to 40 percent you can see now have a 17p.  So you could see it's an evolution, whether it be a clonal evolution or a resistance.  I mean, there's a variety of different implications about what that means, but it increases with time. 

So certainly many of us will advocate rechecking what people's markers are prior to receiving new therapies and things like that because it may alter what you do. 

Carol Preston:

Yeah.  Yeah.  That's a reasonable response.  All right.  So from Michelle, any developments for improving immune system—immune systems that have been compromised by CLL or its treatment?  Yeah, how do we strengthen the immune system? 

Dr. Lamanna:

Yeah.  It's a really good question.  You know, obviously there's old—the old traditional therapies sometimes we've often—many people might be familiar with immunoglobulin or IVIG use in CLL.  That was sort of the traditional approach to patients who were beaten up or who were getting recurrent bacterial infections from their immunosuppressive due to their CLL, so it's a monthly treatment that folks can get. 

But you're right, let's talk about general stuff, what can you do.  People ask about diets all the time.  Should I avoid sugar altogether?  Should I—you know, there's lots of—the Internet is very helpful, but also you have to realize it can be very dangerous too, you know, because you certainly can read about cancer diets but what might be applicable to one cancer may not be applicable to another cancer.  It could be detrimental. 

Carol Preston:

There's a lot of discussion about sugar.  

Dr. Lamanna:

Sure. 

Carol Preston:

I love sugar.  

Dr. Lamanna:

There's implications—I always tell my—okay.  I always tell my folks, I say, look, I think in general if you take care of your body and respect your temple, you know, things that help you from your other medical—you know, if you have cardiovasculars, your heart, your kidneys, things that help you in general, a little exercise, will help you in the long run deal with some of these issues.  But you're right.  There's a paucity of real data.  There's some trials by the Mayo looking at green tea in CLL.  People ask me about that a lot.  I think that there's nothing wrong with that. 

Carol Preston:

That's a lot of green tea that you have to drink. 

Dr. Lamanna:

Okay.  So that's where I was going to go with that.  That was the next step.  I'm in support, but I always say the trials that were run on that were extremely high doses of green tea.  I don't think that most individuals can do that.  Many came off due to GI side effects, diarrhea and so on and so forth.  But if people say, look, I want to do something.  Do I say you can take some green tea?  Yes.  Can you balance it? 

I always tell people if you're going to take supplements, though, let your doctor know.  It's really, really important, because, you know, some of us may feel differently about certain supplements, and I always tell people in moderation is really key.  Taking high doses of any supplement is probably not okay, particularly if it may affect your other organs. 

So I think in terms of your immune system if there's something specific related to treatment that you're getting, you might be able to—it just depends on what side effects you're having, and that you should discuss with your physician because you might be able to—they may be able to offer suggestions depending upon what specifically it is.  But you're right.  There's a lot we have to do with the immune system. 

Carol Preston:

This question from Lynn really speaks to me because I'm always thinking that whatever new therapies come along it's a bridge to the next therapy, and that's what we as patients with incurable cancer are looking for.  So she asks, what drugs are available if an inhibitor, if one inhibitor stops working? 

Dr. Lamanna:

Yeah, fair enough.  We're going to see—there's going to be I think a lot of data over the next coming months to the next few years about this topic.  There are patients who are definitely already progressing through some of the kinase inhibitors now, and as people who—clinical investigators who do CLL and obviously patients who take care of CLL, one of our interests is to see can we sequence from one inhibitor to another?  How long will that response last?  Will it be brief?  Or do you sort of circumvent those pathways altogether and look at different agents that aren't part of the pathway that you—if you had ibrutinib or idela or something like that, do you look to a Bcl?2 inhibitor?  What about synergy between another kinase and a different agent? 

So these are all—the good news is you're right.  We've tried to—we have obviously exploded with the amount of drugs we have in CLL, and we're very happy to have these new agents because it really has given the opportunity for patients who have failed every prior chemoimmunotherapy program that they've had, and now all of a sudden they can get these novel agents.  So the good news is there's a lot going on, but you're right.  We have to sort of figure out what's best for patients who might fail one new drug—one novel therapy, what can they be successfully bridged to. 

Carol Preston:

So that leads me to thinking about the downside of all of this.  With all of these novel or these new agents available you would think, based on the way these therapies work, especially the inhibitors, that—you know, if you're blocking the protein that makes a tumor grow it's going to work in all of the molecules, and it doesn't. And it's very vexing, and it's frustrating.  Why aren't they working? 

Dr. Lamanna:

Yeah.  Well, if anybody has ever looked at one of those pathways, those charts that you can Google, and you look at the B?cell receptor pathway there's lots of proteins, and there's lots of things that we can block and inhibit.  And your body is very sophisticated, obviously a lot more sophisticated than we are up to this point, because we haven't had a cure yet.  We're working on it, but clearly much more sophisticated because if you block one protein your body can find ways to go around and go to another target, and so—or down a different pathway.  And so that's the problem. 

So that you know, just like CLL is really not one disease, and people—there are people who never need treatment and then there are other people who need treatment quite quickly, you can see that clearly there's a lot more about CLL and its biology that we don't understand.  And similarly even though we're thrilled to have these new novel drugs, your body is still sophisticated enough to

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Page last updated on August 5, 2015