ASH 2018 Daily Wrap: CLL News

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Topics include: Treatments and Understanding

At the 2018 American Society of Hematology (ASH) meeting in San Diego, Patient Power founders Andrew and Esther Schorr are joined by leading experts, including, Dr. Nicole Lamanna and Dr. Jeff Sharman, as they review news from the conference. The panel discusses clinical trial data and research highlights with a focus on progress made in chronic lymphocytic leukemia (CLL). Watch day three of Patient Power’s daily wrap to hear the latest blood cancer-related treatment news.

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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:

Hello, from San Diego. I'm Andrew Schorr with Patient Power, and we are next door to the big convention center where they've been meeting for days, the American Society of Hematology meeting where they create news, really, all the latest research for blood-related conditions and most specifically blood-related cancers like chronic lymphocytic leukemia that I've had for 22 years, and if you're watching maybe you or a loved one who has that. And I'm with?

Esther Schorr:  

Esther Schorr. And I've been with it for 22 years as well. So, I'm as interested as anybody else about what's new.

Andrew Schorr:

And this is a positive story for people who are living with CLL, and wouldn't it be great if it can be cured? But certainly we want to have people live a full life, and there are more and more tools to do that. We have an expert panel with us. I will start to introduce them, but I want them to say their titles and where they're from and their institution. So, Nicole Lamanna maybe you've seen before. Nicole, you're where and what's your title these days?

Dr. Lamanna:   

Columbia University, New York. The title's not that fancy, Associate Professor. I'm not sure that's relevant, CLL doc. That's more relevant.

Andrew Schorr:

And, Jeff?

Dr. Sharman:    

My name's Jeff Sharman. I'm actually in community practice in Eugene, Oregon, and I serve as the medical director of hematology research for an organization called US Oncology.

Dr. Lamanna:   

You have a fancier title.

Andrew Schorr:

Jeff, it's all over the country, right?

Dr. Sharman:    

Yeah.

Andrew Schorr:

Right. Okay, and then here's our friend Lee Swanson who's been doing interviews for Patient Power, but, Lee, you've been living with CLL for how long?

Lee Swanson:  

Eleven years almost 12. 2007.

Andrew Schorr:

And you've had to make smart choices even here in San Diego to have the right doctor that you felt comfortable with, and, ultimately, that led to you being in a clinical trial, right?

Lee Swanson:  

That's true. Yeah.

Andrew Schorr:

And he's been doing well. Now we're going to talk about the trial that he's been in fits in with some of the data that's been discussed here. So, should we get on with the news?

Esther Schorr:  

Yeah. What we really want to know is what has got you guys excited about what you're hearing at ASH this year, especially versus last year, because there were some cool things last year as well? What's the update?

Dr. Lamanna:   

Well, there are lots of updates. I think for a highlight probably not very new news for folks who do CLL but finally some presentations comparing chemoimmunotherapy to ibrutinib (Imbruvica). And, again, not surprising to some of us but obviously the data really finally highlighting randomized data, large sets of patients looking at chemoimmunotherapy versus an ibrutinib or ibrutinib and rituximab (Rituxan), again, highlighting the importance of ibrutinib as front line therapy. And so I think as a major take-home I think we're gonna be for the majority seeing probably less chemoimmunotherapy, although there are subsets that I think it's certainly still relevant for, but I think these were nice, randomized studies really highlighting the impact of Ibrutinib as frontline therapy, whether you're old or young and whether you have high-risk features or not.

Esther Schorr:  

So, cutting out chemotherapy as a frontline?

Dr. Lamanna:   

For the majority. I think there are still a subset of patients, if they have favorable disease characteristics, they're mutated, I think chemoimmunotherapy is still a relevant conversation for that subset of patients. But I really think that finally this is the data that many oncologists were looking for is just randomized data showing is this better than chemoimmunotherapy, that unanswered question for years, even if we were adopting it differently in different practices? This really was finally data that was put out there.

Andrew Schorr:

Let's just be a little more specific. Patients for years have heard about FCR or BR, so being cyclophosphamide and rituximab. That's that chemo.

Dr. Lamanna:   

One chemoimmunotherapy.

Andrew Schorr:

Another one would be bendamustine (Treanda) and rituximab. Okay, so that's FCR or BR. Are you saying now we're talking about IR for example?

Dr. Lamanna:   

If you look at the data a little bit more closely, the question of whether or not monoclonal antibodies such as rituximab adds a significant impact to ibrutinib therapy. And so I think that many of us feel that adding rituximab to ibrutinib may not add that much. And so some of these randomized studies that looked at bendamustine-rituximab versus ibrutinib versus ibrutinib-rituximab that there was really no different between the ibrutinib and the ibrutinib-rituximab arms. I think that many of us don't feel that you necessarily need the rituximab as part of ibrutinib therapy. They were both equally efficacious.

Andrew Schorr:

And there's more. Other studies, there were a lot of studies coming out, so what else, Jeff?

Dr. Sharman:    

I would actually say this is the year for CLL. I've been coming to ASH for 15 years or so, and every year sometimes it's good for one cancer. And other cancers, there's not a whole lot new, and you get back to your practice and people say what's new? CLL has had a great year, and to echo Nicole's comments, a lot of questions have been answered regarding correct frontline management of CLL. To sort of piggyback from what you said, when we do clinical trials, there are different goals of why you do a clinical trial. Sometimes it's to answer what's the best way to do something. Sometimes you're trying to answer can I get this drug approved and get access to patients?

And so, one of the studies that had been out there for a long time was ibrutinib versus chlorambucil. I almost kind of feel like that study was verging on unethical. I think we knew what the results were gonna be, and you want some measure of equipoise, some uncertainty like you might not necessarily know what the outcome's gonna do. That's why you do the experiment, but ibrutinib had never been compared to what we would call real therapy and chlorambucil sort of being almost not a real therapy. So, bendamustine, rituximab, fludarabine (Fludara), cyclophosphamide (Cytoxan), rituximab, really the regiments you have been using over the last 10 years to say, oh, we're gonna get your CLL under remission, this now puts in a real clean head to head situation.

When you do that, there are a lot of sub questions you can answer, and you were talking about maybe there's some subgroups and so forth. I don't want to get too technical, but I think there's value in highlighting some of these, because I think you've got a pretty sophisticated audience. One of the big dividing lines in CLL is whether you are what we call mutated or un-mutated. It has to do with what we call the b cell receptor. Sometimes you see it referred to as IgVH mutation analysis, but the patients who are mutated tend to have better outcomes. The patients who are unmutated tend to have less good outcomes. When I say less good outcomes, the chemotherapies can still get the disease into remission, but oftentimes those remissions aren't as long-lasting. So, I think it's very clear that novel agents, such as ibrutinib, in those patients who are unmutated, it's hard for me to justify using chemoimmunotherapy in a patient who's got un-mutated B-cell receptor.

Dr. Lamanna:   

Agreed.

Dr. Sharman:    

Conversely, in the mutated population the question is those patients are going to oftentimes get a better response to chemoimmunotherapy than their unmutated counterparts. So, there may be a closer approximation there. There are two main frontline studies: ibrutinib-rituximab versus FCR, and then ibrutinib against BR versus ibrutinib-rituximab. We haven't seen the ibrutinib-rituximab versus FCR. That comes out tomorrow morning, but really in all groups, advantage ibrutinib. Who would you give FCR to anymore? Boy, that's a small group of very young, very fit, very robust patients who are committed to a short duration therapy who have the most favorable molecular features. That's the only group where I would use it.

Andrew Schorr:

I just want to get Lee's impression for a minute. Lee, you've been also doing interviews as well as living with CLL. How does this sound to you and from what you've been hearing in other interviews?

Lee Swanson:  

Well, I think it's good news all the way around. If you can avoid chemotherapy, that's good.

Andrew Schorr:

You had FCR.

Lee Swanson:  

I did. And on the other hand you know going into FCR it's a six-month regimen, and you're out. If you're on ibrutinib now instead frontline, are you there forever?

Dr. Lamanna:   

I think that there are obviously many questions this raises. Obviously, we're gonna talk a little bit more about indefinite therapy versus not. I think what Jeff and I are really just saying is this is at least the first real randomized data showing the importance of a BTK inhibitor or Ibrutinib in this case versus chemoimmunotherapy. So, when we look at these therapies, obviously, like Jeff said, there was a lot of data and presentations that made this year extremely exciting for CLL at ASH like it did many years ago when Ibrutinib first got approved. So, we have, obviously, a lot of exciting combinations and things that are going on, but at least this was some maturity of data that we had of ibrutinib versus chemoimmunotherapy.

Will that stay that way? No, I don't necessarily think it will, but at least I think it solidifies that the novel agents, there are better responses. And chemoimmunotherapy is fading a little bit more in the background with maybe some very select groups. What Jeff was highlighting about the mutational status is very important for patients to know, because I think many of us had already felt that data participating in these clinical trials that those individuals really shouldn't be treated with just chemoimmunotherapy that the un-mutated IgVH patients really should be treated with novel agents. And so that's very an important take-home point.

Esther Schorr:  

So, for kind of the uninitiated or the novice new patients of CLL.

Dr. Lamanna:   

We always talk about 17P, but it's also the mutated or unmutated.

Andrew Schorr:

You are going to have questions, and we'll get to some a little later in this group. We're gonna go 45 minutes or so.

Esther Schorr:  

We already have some questions.

Andrew Schorr:

Oh, we've already got some. And we're gonna get to those, but I want to get to more of the news too. So, if you have a question, send it to [email protected]

Esther Schorr:  

And it will come to us.

Andrew Schorr:

Yeah, we'll get it, and then we'll triage it, do as many as we can. We have a lot of ongoing CLL programs. If you don't have CLL and you're watching and saying what's going on at ASH, we have done other daily wrap-ups. There was one the other day that focused on MPNs and the replay is on the patientpower.info site. Probably tomorrow we'll publish the one that we specifically discussed multiple myeloma. We've done interviews in AML. In Hodgkin lymphoma, we've done lots of interviews. Lee, we did some in T cell, peripheral T-cell lymphoma, follicular lymphoma. We had Dr. Wong who's so excited in mantle cell lymphoma, so it'll all be there in the Patient Power website. We're gonna have sort of a focus on CLL questions at patientpower.info. Here's my next thing I want to discuss. Combinations. We've had these combinations F and C, and then FCR or BR. Now we have this I maybe with R, but also this man received Venclexta or venetoclax, right, in a trial called the MURANO trial. And that's enabled him to stop therapy right now. That's what we had with FCR-BR. You have it, and then you're done. Hopefully, a long remission, I had 17 years, yay, very long remission. So, what about that I mean because these pills are expensive? Where are we headed with that?

Dr. Lamanna:   

This is very exciting data. And since you're part of it, thank you for participating in a clinical trial, because we can't thank patients enough for doing that ,because that's how you move the field forward and answer many of these questions. Clearly, this was an update, so it wasn't that the study is new. The MURANO data was presented before, but, clearly, this was an update looking at three-year data. And so this was a relapsed trial, so patients who had already been treated for their CLL.

Andrew Schorr:

We had FCR, six heaters, and then had Rituxan and then venetoclax.

Dr. Lamanna:   

Correct. This was looking at patients who were randomized to receive either venetoclax and rituximab versus bendamustine and rituximab. And the data was overwhelmingly favorable for the venetoclax and rituximab both in responses and progression-free survival. Then there was this sense of can patients get deep levels of response and be in not just regular routine response criteria when we think about patients in remission but also to deeper level where we detect very few residual leukemia cells? And what does that mean? How to interpret that data and then stay, as you know, you received for only 24 months the venetoclax was stopped.

So, instead of indefinitely staying on an oral therapy like ibrutinib for a prolonged period of time until you either have a side effect or you progress but having a finite period of time on an oral therapy, stopping the treatment, and then being monitored. And then having the ability if the disease comes back again, the protocol was amended to allow patients to reinitiate therapy. This is really exciting data, and, obviously, when we talk about doublets and triplets and different combinations whether or not we can utilize data like this and have patients not have to from a cost perspective or even a toxicity perspective be on indefinite oral therapy. Can we give patients a break similar to—and, again, this is different—to chemoimmunotherapy when you add FCR?

You had six months of treatment. You were done, right? You were monitored until the disease progressed again until you re-needed therapy again. Can we do that in the light of the oral therapies but maybe even get to a depth of remission that's even finer, because now technology has gotten incredibly more sensitive. Can we get better and really look at that data and inform proper decision-making about depending upon the patients disease characteristics, do we need X amount of therapy, or should we have this go on for 18 months, 24 months, 12 months and then allow people to have a drug-free period. and then can they reintroduce the same drug later on if they progress and be sensitive again to the same agents?

Andrew Schorr:

This man is a year-and-a-half out now, no medicine.

Lee Swanson:  

More than that, yeah.

Andrew Schorr:

No medicine.

Esther Schorr:  

But if you end up going in that direction and there's a gap, you treat it, you're not treated, you're monitored, do you then need to go through? Would you need to then go through the testing again to see if something's changed in the type?

Dr. Lamanna:   

Yeah, absolutely. I mean, I think that's important, right? So, not only are we trying to detect when the disease comes back again, is the same, right? So, exactly. I think that's important to look at. What we're learning by capturing this data on a trial such as the MURANO trial is how long will that response duration last? And I think John Seamore really presented data showing about the detection of different levels of these of these leukemia cells regarding minimal residual disease, and how long would that last? I think, obviously, we need longer follow-up, but it gives us a little bit instruction, I think, about how comfortable we are about, perhaps, doing time-limited duration.

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Page last updated on January 25, 2019