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

How Are CLL Patients Responding to Treatments?

Read Transcript Download/Print Transcript
View next

Published on January 10, 2020

Key Takeaways

  • Research updates on navigating CLL treatment option choices
  • Safety concerns should patients should think about when choosing treatment
  • How to weigh options between fixed duration or long-term treatment

Noted chronic lymphocytic leukemia expert Dr. Jennifer Woyach joined Patient Power as part of our coverage of the 2019 American Society of Hematology (ASH) Annual Meeting & Exposition. Watch as she provides a report on response and remission duration data from large CLL clinical trials comparing different treatment regimens. Dr. Woyach also describes the advances in understanding the underlying genetics of cancer, and how doctors are tailoring treatment plans to CLL patients.

This program is sponsored by Pharmacyclics and Janssen Biotech. This organization has no editorial control. It is produced by Patient Power, and Patient Power is solely responsible for program content.

Featuring

Transcript | How Are CLL Patients Responding to Treatments?

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.

Michele Nadeem-Baker:

Thank you for joining us.  This is Michele Nadeem‑Baker, and I'm with Dr. Jennifer Woyach, and we're here at ASH 2019.  We're talking about CLL today.  I just got out of a presentation where you and there was a panel and you were speaking of a lot of different advances that are happening but went into great depth of how perhaps being able to predict patients—being able to determine what someone has.  What will that prove for patients?  How will that help patients? 

Dr. Woyach:

So there are a lot of really exciting things going on at ASH.  I think what's—we're learning more and more in CLL is we've always known it's a heterogeneous disease.  We're getting better at figuring out how to put patients into groups, like who is likely to do well with this therapy, who is likely to do well with this therapy, who will do well with any therapy.  And then with that knowledge we can better tailor our frontline approaches and our approaches for patients with relapsed disease. 

Michele Nadeem‑Baker:

What's the biggest news that you've heard here? 

Dr. Woyach:

So there has been a lot of follow‑ups of large trials that I think have been really interesting at this ASH.  So there was follow‑up of about a year from the German CLL Study Group, CLL14 study which was venetoclax-obinutuzumab (Venclexta-Gazyva) versus chlorambucil-obinutuzumab (Leukeran-Gazyva).  And in the previous follow‑up it was only one year after patients completed therapy, so a big question on everybody's mind is are these remissions actually durable. 

So now with an additional year of follow‑up we can see that, yes, most patients are retaining those remissions, especially those who have IgVH-mutated disease, those who don't have p53 abnormalities, so kind of our better risk patients, tend to do best with that regimen. 

We also saw follow‑up from the ECOG 1912 study.  That was the Cooperative Group US Study comparing ibrutinib-rituximab (Imbruvica-Rituxan) FCR in younger patients.  And importantly the progression‑free survival advantage of ibrutinib-rituximab was maintained, and as well the overall survival advantage was maintained too. 

And then one of the biggest new things the Elevate TN Study, which was the first Phase III trial of acalabrutinib (Calquence), so a second generation of BTK inhibitor, in patients with treatment‑naive CLL, and so that study was chlorambucil-obinutuzumab again versus acalabrutinib alone versus acalabrutinib plus obinutuzumab. 

As everybody would expect, acalabrutinib and acalabrutinib obinutuzumab was better than chlorambucil obinutuzumab, but the data at the follow‑up that they have—so it's 28 months average follow‑up, so at 24 months about 90 percent or even a little higher of patients treated with an acalabrutinib or acalabrutinib regimens are still in remission. 

Michele Nadeem‑Baker:

Now, I have a question on two studies prior to the last one of spoke of.  You were talking about ibrutinib and—versus FCR, so it was ibrutinib and…

Dr. Woyach:

...it was ibrutinib-rituximab (Imbruvica-Rituxan) and FCR. 

Michele Nadeem‑Baker:

And that's a trial where—we have many patients watching with unmutated IGHV, so that's the one where they did better versus the FCR, then, treatment? 

Dr. Woyach:

Correct, yeah.  

Michele Nadeem‑Baker:

That's great you news for them. 

Dr. Woyach:

Yeah.  The magnitude of benefit was much higher for those patients with IgVH-unmutated disease. 

Michele Nadeem‑Baker: 

Because we have some people who follow up who are IgVH-mutated—I pay attention to that especially because I am—that were still being put on FCR.  And is that something that's going—for unmutated is that something going by the wayside now? 

Dr. Woyach:

It should go by the wayside.  I think we have a lot of data now to say that people who have IgVH-unmutated disease or those that have TP53 abnormalities, so like a mutation in that gene, or a deletion 17p, those people really shouldn't be treated chemotherapy anymore, because our targeted therapies are better.  

Michele Nadeem‑Baker:

Have you had any surprise news here that you weren't expecting to hear about?  

Dr. Woyach:

I'm not sure if there have been so many surprises so far.  One thing that has been interesting that we didn't really have data on before is—we've always‑‑we've known that you could put a patient on ibrutinib and if they progress on the ibrutinib could switch them to venetoclax (Venclexta).  There was a large study showing that to be the case.  Now we have small data but from a few different places showing that potentially the reverse is also true.  So somebody who has been on venetoclax first they could then go to ibrutinib and do well. 

Michele Nadeem‑Baker:

Is one better than the other? 

Dr. Woyach:

That's a great question, and we really don't know the answer.  One of the questions I was asked in the session we were just at is would it be good to do a trial like that were where you actually examine the two sequences head‑to‑head.  Personally, I'm afraid that a study like that is going to take so long that we won't know if it's meaningful by the time we get to the end of it, but I think as more and more data come forward showing that you could use them kind of interchangeably after each other, that will make everyone feel more comfortable and when you're in the front‑line setting just choosing the therapy you think is best rather than trying to predict the future. 

Michele Nadeem‑Baker:

A couple things I've been seeing and it was in your sessions, some others that just going with monotherapy may become a thing of the past?  

Dr. Woyach:

I don't‑‑I'm not sure about that.  So for some patients it might, and there are two large Cooperative Group studies that are trying to address that question in the United States.  So there's an ECOG, EA9161 Study and the alliance AO41702 Study, so those are like younger patients and older patients, looking at ibrutinib plus obinutuzumab versus ibrutinib-venetoclax and obinutuzumab using different time limited approaches really to see whether at least for ibrutinib versus the ibrutinib-venetoclax combinations which one of those is better. 

Michele Nadeem‑Baker:

Now, with all of these choices and all of these trials, and some are looking for patients now, how does a patient know which way to go with all the choices?  

Dr. Woyach:

Well, hopefully you have a good relationship with your physician and you guys could really have just discussion about for your type of CLL what kind of efficacy can you expect from these regimens and also what safety considerations might be present for you.  So we know that there are certain people who are likely have more side effects with ibrutinib, for example, maybe even versus acalabrutinib, but there are different side effect profiles for BTK inhibitors and for venetoclax, and I it's really an individual patient decision. 

So it comes down to expectations of efficacy, safety, and then a lot of intangible things too.  Like do people have a preference on a fixed duration versus indefinite treatment?  Do they want to come for the ramp-up of venetoclax and to get the obinutuzumab infusions, or would they rather take a pill.  So I think there's a lot of things, and really I would encourage people to really have a decision about that with their physician because that's the reason why we all went to medical school and I'll go to these conferences so that we hopefully will have some answers to help you guys make decisions. 

Michele Nadeem‑Baker:

Which all patients really, really appreciate.  And, Jennifer, what about your love?  What are some of the things you're working on right now? 

Dr. Woyach:

Yeah, so my incentive at laboratory is mostly focused on developing new therapies for people who have relapsed on our current novel agents.  So we're looking at drugs that we think might be effective in patients who relapse after ibrutinib, for example.  So one of the big things we've been looking at are the reversible BTK inhibitors.  So when people relapse on ibrutinib or acalabrutinib, for example, many of them will develop mutations in BTK, and there are actually drugs that have been developed to overcome these mutations, and so we're looking at some of those drugs and some other like really novel agents and targets to see if we can find better new therapies.  

Michele Nadeem‑Baker:

Would we know any of the names of those? 

Dr. Woyach:

Yes.  So a couple of those reversible BTK inhibitors have been presented either before end of this meeting or are coming out for the first time at this meeting.  So the first one that has been in development is Sunesis' vecabrutinib, and that's been shown a number of times.  They're in a Phase I study.  AR2531 again is in a Phase I trial updated data is being presented at this meeting.  And then LOXO‑305 is the newest, one and that one, the first data is being presented at this meeting too.  

I think really encouragingly all of them are showing benefit and showing benefit in patients who did relapse on ibrutinib, so exactly what we had hoped we would see. 

Michele Nadeem‑Baker:

So if you had a message for CLL patients what would it be, for the times we're in now in medical discoveries?  

Dr. Woyach:

I think there's never a good time to have CLL certainly, but we're in a period right now where our therapies are becoming better and better and safer and safer, and I think that there's really a lot of hope right now.  There's a lot of new things.  There's a lot of like making our current things better, and this is a good time to get treatment for CLL if you're going to need treatment for CLL. 

Michele Nadeem‑Baker:

Do you see a cure in sight any time soon? 

Dr. Woyach:

I don't know.  There are a lot of agents that have this potential that maybe after 10 years we'll see that some patients are being cured with some of these regimens, I think especially those IV combinations or AB combinations with a BTK inhibitor with a Bcl‑2 inhibitor with or without an antibody, those are really exciting, and everybody is kind of hoping those might be a cure, but it's going to be a long time before we know.  

But one thing that I try to stress with my patients is it's actually not all about cure.  It's about making the lifespan of somebody with CLL the same as somebody without CLL and doing so in a way that people have really good quality of life.  And for me I think that's a reasonable goal too.  So if we can have somebody CLL doing the same as somebody who has high blood pressure then I think that we are really making progress. 

Michele Nadeem‑Baker:

That is a really great goal for all of us to have.  Thank you so much, and that was a really good hopeful comment for all of us. 

Dr. Woyach:

Great.  Thank you. 

Michele Nadeem‑Baker:

Thank you so much.  For Patient Power, live from ASH, this is Michele Nadeem‑Baker and Dr. Jennifer Woyach.  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.

View next