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

New CLL Therapies Lead to Improved Patient Outcomes

Read Transcript
View next

Published on April 28, 2020

Key Takeaways

CLL Therapies Have Improved, Leading to Better Outcomes

“Where we are today, compared to when I started my career, it's like night and day—the vast majority of people stay in long remissions,” says Dr. Ian Flinn, a chronic lymphocytic leukemia (CLL) expert from Tennessee Oncology. Dr. Flinn and Nurse Practitioner Camille Ballance discuss the evolution of CLL therapies with Patient Power Co-Founder Andrew Schorr.

In this segment from our recent virtual town hall meeting, they explain which new combination therapies are reducing side effects and improving patient outcomes. They also discuss chromosome mutations, FISH analysis and more. Watch now to learn from CLL experts.

This program is sponsored by AbbVie, Inc., Genentech, Inc. and Adaptive Biotechnologies. These organizations have no editorial control. It is produced by Patient Power in partnership with Tennessee Oncology, Bag It, and CLL Society. Patient Power is solely responsible for program content.   

Featuring

Transcript | New CLL Therapies Lead to Improved Patient Outcomes

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.

Esther Schorr:

Hi there, this is Esther Schorr. Recently, Andrew and I co-hosted a virtual town meeting and learned from leading CLL experts about treatments, clinical trials and lots more. Let's listen in as we navigate through a CLL diagnosis.

Andrew Schorr:

So for most people, the oral therapies that we have now, Ian, are working pretty well right now, right?

Dr. Flinn:

Yeah, they absolutely are, and it's amazing. Your journey with the disease, my career in CLL, where we are today compared to when I started my career, it's like night and day. So the vast majority of people stay in long remissions with one of the therapies we've just mentioned, but there is a need for new therapies, there is a need for better tolerated therapies, and so that's really where the research is.  

Andrew Schorr:

So related to the effect of the medicines, and maybe we could go through it. So let's start with ibrutinib, or Imbruvica. What are the typical side effects, do you make dose adjustments? Some of the people have written in, Esther, I think you saw it. "Could I be on a lower dose?" So where are you with that, related to what people should expect?

Dr. Flinn:

Yeah, I mean, I think the most common side effects with Imbruvica or ibrutinib are muscle or joint pain, diarrhea. Usually not severe diarrhea, but a little bit of diarrhea, which can usually be managed with (loperamide) Imodium. There's a risk of atrial fibrillation, and I think that depends on how old you are, but there's a significant risk of atrial fibrillation, and that continues on treatment for a while.

Long term, there's also risk of hypertension that can occur with it, and of course all these drugs, as Camille was saying, people can get rashes as well. Now as it goes with the dose, sometimes we have to hold the medication, because they're having significant side effects. And then once they've gotten over that, we'll start at a lower dose and work our way back up, see if we can get to a good dose. And I know there's a lot out there about people wanting to be on a lower dose, and they are, but unless someone is having side effects—and the other thing to know is that the vast majority of people tolerate these therapies well. They don't have significant side effects.

And if you're one of those people, then I don't see any reason why to reduce the dose. We know you can go much higher than the doses we give. In clinical trials we did originally, much higher doses were used. Mantle cell lymphoma, higher doses used, so we know that people can take higher doses. So I think that we know that the efficacy is good, outcomes are great with the standard dose. I don't dose reduce unless forced to.

Esther Schorr:

So, Dr. Flinn, I'll interject since we're talking about especially ibrutinib, and you just talked about the potential negative side effects, a range of them. But I'm getting some questions from people in the audience about there are some articles published that there may be some positive side effects. For example, one person mentioned that they'd read something about ibrutinib helping to be preventative against, say, prostate cancer. Are there some positive spins that are beyond controlling CLL?

Dr. Flinn:

I'm not familiar with the prostate cancer data, so I'd have to look that up. I think in some ways Imbruvica helps with your immune system, in other ways it doesn't help, and there are risks with immune systems. So I think certainly getting someone into remission, getting rid of all the disease-related symptoms that you're having, and regaining basically a normal life is a very positive outcome. I should have mentioned with Imbruvica, there's also a bleeding issue that can occur, people can get some usually minor bleeding. There was some speculation that maybe this would help with cardiovascular issues. To date, I haven't really seen any convincing data that that's true, but it's a hypothesis. 

Andrew Schorr:

Right. Let me just go over one thing in the treatment choice. So somebody might have some heart issues, and so knowing about Imbruvica related to this concern in some patients about atrial fibrillation, that might mean that you would choose a different way to go, right? I mean, it might be venetoclax (Venclexta).

Dr. Flinn:

So, in fact, if someone was on ibrutinib and they had an adverse event side effect, one reasonable thing is to try them on acalabrutinib (Calquence). But you can avoid the issue altogether if you used venetoclax, right? Especially in a frontline setting, if you used venetoclax with a combination with obinutuzumab (Gazyva), then you could avoid those issues altogether. That has its own side effects, own adverse events, but…

Andrew Schorr:

…let's talk about that. Yeah, go ahead. 

Dr. Flinn:

Well, I mean, I think the thing that people worry about most with venetoclax, the thing that even today makes some doctors afraid to give it, something called tumor lysis syndrome. Tumor lysis syndrome is an issue when you give someone a medication, and all of a sudden all the CLL cells die at once. Now that kind of sounds like a good thing, right? You're killing all the CLL cells, but the problem with that is that when you kill all the CLL cells at once you release potassium, uric acid, mess up electrolytes, and very early on in the development of venetoclax there were a couple of deaths from this.

Now we've learned how to give it safely, we ramp it up slowly. Camille spends a considerable amount of time walking through people in the first five weeks. Each week you go up on the dose, and then if you do that, then it can be given very, very, very safely. The other side effects with venetoclax, sometimes people get some of that joint pain and muscle aches a little bit, but the other one that we face all the time is lowering your neutrophil count, right? The neutrophils are the ones that help you fight off bacterial infections. And so if you get it very low, then you can get life-threatening infections. 

Sometimes you have to titrate, and I think it's about 50 percent of patients that ultimately end up on a different dose than the prescribed 400 milligrams, which is the target dose. So those are the major side effects, I think.

Andrew Schorr:

Okay, and related to venetoclax, it is used often with a monoclonal antibody, typically I think obinutuzumab now, or Gazyva, right? And that's to give it a bigger bang, where maybe you can get to this MRD-negative status and be able to stop.

Dr. Flinn:

Yeah, that's exactly right. There's definitely synergy here, right? I mean, it really looks like these two drugs used together is better than them used separately, than the sum of their parts. And so with that there was a very large trial that was done predominantly in Germany, where they looked at this combination, and it got to very high MRD-negative rates, whether you're talking about peripheral blood or the bone marrow, or the body altogether. It was pretty unprecedented at that time, high MRD-negative rates. Yeah, it's very effective, and it's now an FDA-approved combination.

Andrew Schorr:

Okay. So just to go over the approvals where we are today as we do this. We have ibrutinib used by itself, we have acalabrutinib used by itself, we have Venclexta, I think, used by itself or with obinutuzumab (Gazyva), or maybe even rituximab (Rituxan), I'm not sure. 

Camille Ballance:

So…

Andrew Schorr:

…go ahead, Camille. Sure, you can tell us. 

Camille Ballance:

So yeah, we typically in the frontline setting we do venetoclax and obinutuzumab, and then if a patient's relapsed, then it's venetoclax and Rituxan, is what's approved. And there are different time limit therapies for that, so if you're in a relapse setting, the recommendation is two years. Frontline with venetoclax and obinutuzumab, the recommendation is one year. 

And as far rituximab is concerned, I was just going to say that I tell patients a lot that the neutropenia with that drug concerns me more than the tumor lysis. Like Dr. Flinn said, everybody freaks out about the tumor lysis, but we know how to manage the tumor lysis very well because of the way we do it. I mean, I look at those labs, and we can get right on top of it before anything really gets bad.

But the neutropenia, I mean, we give patients—I feel like I spend a lot of time, especially on some of the trials we have, trying to manage the neutropenia that occurs with that.

Andrew Schorr:

But you have ways to do that. 

Camille Ballance:

We have ways to do that. There's no reason to not want to be on that drug at all because of it. But that's just something that patients need to be aware of, that the neutropenia can be there, and that that needs to be monitored.  

Andrew Schorr:

One thing I'll ask you about, so going back a number of years, there were some people, very aggressive forms of CLL who had a stem cell transplant with donor cells. Is that all gone now?

Dr. Flinn:

I wouldn't say it's gone, but it's really rare. We used to say if someone has a 17p deletion, one of these unfortunately difficult, poor prognostic factors, then they need to go to transplant. Actually, not true anymore, we definitely don't do it. I have done it in the last couple years, but it is rare that someone needs an allogeneic transplant, a stem cell transplant. 

Andrew Schorr:

Could you explain this 17p? People get these blood test results, they see the pathology report and it says, "11q or trisomy this?" What are we talking about, and what does it mean?

Dr. Flinn: 

That's definitely an important thing for everyone to understand. So you can think we're looking at the chromosomes within the CLL cells. The best example I think most people can relate to about looking at the chromosomes is looking at a child in utero. Sometimes we get these checks of the chromosomes to make sure the child doesn't have Down syndrome or some other defect. Well, we can do that same analysis on the CLL cells from the peripheral blood or the bone marrow, and we do that, we do that karyotype that's called, we can pick up an abnormality in, say, 35 or 40 percent of patients.

But using a more specific way of using what's called FISH, fluorescence in situ hybridization, we can use probes, we can pick up an abnormality in about 85 percent of people. Some of these abnormalities are actually good, so someone who has a 13q deletion, basically missing part of the 13th chromosome, that's actually a good thing and a little bit more than half of patients will have that. Now, there are some abnormalities that are bad. The missing 17p, missing part of the 17th chromosome is a bad thing to happen prognostically, and that localizes to a gene called p53, and there are a few more people, even if the chromosome's intact, but you look at the sequence in that gene you find abnormalities as well.

But I think one of the important things with these is that this used to be unfortunately a very horrible prognosis for people, but with the new agents a lot of that horrible prognosis has been overcome with some of these newer agents. It's not completely overcome, you'd prefer not to have that, but the outcomes are much better for these very high-risk patients. 

Andrew Schorr:

Related to people who are told they're mutated or unmutated. So it'd seem like unmutated is good, everything is staying the way it's supposed to be you'd think, but I hear that in CLL, unmutated is better. So what are we talking about? 

Dr. Flinn:

All blood cells and other cells in our body go through a normal life cycle just like we do, right? So you'd start out as a baby, an infant, you grow to an adolescent, an adult, senior citizen, and ultimately the cells are supposed to die off, right? So where in that normal life cycle the transformation from a normal cell to a malignant lymphocyte occurs is of prognostic importance, and so it's better to have it happen later in the life cycle.

And it turns out that that's in a mutated immunoglobulin heavy chain versus an unmutated is a younger cell. Yeah, I think this is the only time that it's ever good to be mutated, right? Pretty much anything else, and I think you need to make sure we're not talking—because sometimes we do next-generation sequencing, and we look at individual genes. And we're looking for mutations in those, and in those cases, it is bad to have most of those genes mutated. 

Andrew Schorr:

So, Camille, so you probably have gone over some of these pathology reports, how do you help people calm down? How do you help them? 

Camille Ballance:

Well, I think it's just reiterating what Dr. Flinn said. I think the big thing is repetition honestly, because a lot of this is hard to process. I mean, it's a lot. I mean, trying to even understand how a blood cancer works is overwhelming, and so I think it's just reassuring them if they have the 17p that there are great options for them now. And that even in that case that if they're doing okay, we're not going to treat them until we absolutely have to, right? And so it's just having, I think, a lot of conversations to try to make them understand their disease, which takes more than one conversation. 

Andrew Schorr:

Right. Could we get into managing expectations when you and Dr. Flinn have prescribed one of these newer medicines, as to what to expect? Testing, possible side effects, management of side effects, you want to take us through that, Camille? 

Camille Ballance:

Sure. Well, obviously it depends on what medication that has been decided to give the patient. But with some of the novel agents, I will say there tends to be more issues with rashes with oral medications, the skin's more sensitive. The nausea and vomiting is obviously not there like it would be for patients that we've had to put on chemotherapy, but it can be there, it's just not as severe.

Sometimes there can be some muscle and joint pain. A lot of times some of these side effects too, especially if you're on the oral medications, happen early on. So if we can get them through that initial period, there's a lot of reassurance there in terms of—I tell patients all the time, "We need to get you through this first four to eight weeks," right? Depending on what they're on, what they are. Especially because they're coming in to the clinic more, because we're checking their counts, because these drugs can drop their counts.

Usually they end up leveling back out, especially once they're off—if they're on obinutuzumab or an antibody with it, they can definitely drop it even more, and so once they get a couple of cycles of that or they're off of that, things get better. But yeah, I think those are the main things, it just really depends. And I think too, a lot of what I do is tell them how often they need to come in to the clinic in the first few weeks, as opposed to once they're stable we don't have to see them as often.

One of the biggest things they want to know is, "How often do I have to come here, and how long am I going to have to be on treatment?" Those are the two things we talk about a lot. 

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.

Recommended for You

View next