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Clinical Advances Announced at iwCLL

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Published on October 28, 2019

Chronic lymphocytic leukemia (CLL) expert Dr. William Wierda from The University of Texas MD Anderson Cancer Center joined Patient Power to discuss promising research for the treatment of chronic lymphocytic leukemia (CLL) announced at the International Workshop on CLL (iwCLL) 2019 in Edinburgh, Scotland. How do advances in the lab translate to the clinic? How can patients determine which strategy is right for them? Watch as Dr. Wierda gives updates on minimal residual disease (MRD) testing, expanding treatment options and improving remission duration for those living with CLL. 

For more information about the conference visit www.iwcll2019.org

This program is sponsored by CLL Global Research Foundation. This organization has no editorial control. It is produced by Patient Power and Patient Power is solely responsible for program content.

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I consider myself a pretty well educated CLL patient but there was much presented today that was new to me, and much more that expanded upon what I already knew or filled in missing bits of information.

— CLL Event attendee

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CLL Global Research Foundation

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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.

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:            

Well, hello everybody. This is Esther Schorr with Patient Power. I'm coming to you from actually La Jolla, California. And I'm delighted to have our dear friend and wonderful CLL expert, Dr. William Wierda, with us from MD Anderson, who we all know is an amazing CLL expert and has been with Patient Power many times to share his—his wisdom.

Dr. Wierda, I know that you have just returned from iwCLL in Scotland, and it sounds like there might have been some really interesting things that came up that would be of interest to CLL patients. Can you talk to us a little bit about that?

Dr. Wierda:                

Yeah, sure. So thank you for having me. And it's good to see you, Esther, and I'm glad to hear Andrew's doing well. We had a great meeting. Actually it was a three, four day meeting—three-and-a-half day meeting with updates, both laboratory investigations and discussing new data that's being generated from laboratory studies as well as updates on clinical trials, and advances in—in therapy.

I think patients are usually more interested in the clinical advances, so I might—maybe just focus on that and—and highlight some of the things that we reviewed and talked about.

We've very excited about the combination therapies that we're developing with small molecule inhibitors. Combinations of ibrutinib (Imbruvica) plus venetoclax (Venclexta), where we're able to get most of the patients who go on these treatments in very deep remissions, to the point where we're—we don't have any detectable residual disease, either in the in the blood or in the bone marrow, what we refer to as MRD negative, with a fixed duration of treatment, where patients can have a year or two of therapy, be in a deep remission, and achieve an undetectable MRD status and then come off treatment and anticipate a long duration of remission off treatment without worrying about having to experience any side effects or toxicities if patients are in remission, and they're just being observed.

The question in my mind will be with those new strategies are we able to cure patients? And hopefully we’ll be able to generate some data along those lines and it's going to take some time because patients have to be observed for a period of time before we know that the remission is durable and that this disease stays away, but I'm very optimistic about the deep remissions that we're seeing with the small molecule inhibitor therapies, combinations of BTK inhibitor, plus Bcl-2 with the addition of CD20 antibodies.

So there was a fair amount of discussion about that. We learned also about—a little bit more about venetoclax based therapy and we've had discussions and we're working on reviewing our data really to know what the fixed duration—the optimal fixed duration of treatment is. Should patients be treated for a year? Should they be treated for two years? And that also has lead to a lot of review and discussion about the MRD data that we're generating. Minimal residual disease is an important endpoint, and I think we'll see more about that in the clinical trial designs.

I think all of the clinical investigators; all the people who are developing new treatments and developing new clinical trials in CLL are very interested in including MRD as an endpoint into the clinical trials. We see less of that yet in the community practice. It's not yet reached prime time and community practice, but in terms of the clinical trials that we're doing, clearly it's an important endpoint and it's an endpoint that we'll see included in the studies. 

So there's a lot of very exciting work that's being done. Patients—more patients now than ever we have in deep remissions, and are MRD negative. I can't think of a time in the past where I had more patients coming to see me in clinic who are in remission and were MRD negative than—than the current time. So we're all very interested and excited.

There are a lot of treatment options now. And there's discussion. And I think we'll have more data at ASH about additional trials that are ongoing and what's the best first line management strategy and strategy for management of relapse disease. 

Esther Schorr:            

Dr. Wierda, you talked a lot about testing and MRD negative testing. I know there's a lot of conversation between patients about the relevance of being MRD negative, coming out of treatment. Can you comment about that? 

Dr. Wierda:                

Sure. So if we're talking about treating for a fixed period of time. With chemotherapy, or chemoimmunotherapy it was usually six cycles of treatment. But with the newer targeted therapies it's going to be a longer period, either a year, or two years. At the end of that fixed duration of treatment we do an assessment, a response assessment. For the clinical trials that include a CAT scan to see if there are any residual lymph nodes that we can measure. It also should include a bone marrow. And the bone marrow is used to determine if there are any leukemia cells there.

There's a special test that we do, called the minimal residual disease test. There's different ways that that can be done. It can be done by a method called cytometry. It can be done by gene sequencing methods, or NGS-based methods, but that test allows us—or those tests allow us to determine if there are any leukemia cells beyond what we can identify by a microscope.

It allows us—and when we talk about MRD we talk about a level of sensitivity where we strive to be able to detect one leukemia cell among 10,000 normal cells. So that's the limit of detection that we use as a standard when we talk about MRD. So if we say a patient is MRD-negative, we are doing a test and there are fewer, or less than one out of 10,000 leukemia cells present in the bone marrow.

The importance of that is if patients are negative in that testing then that correlates with a much longer remission than if there is detectable disease there. 

And in the chemotherapy era we also were making correlations with survival. Longer survival being associated with a deeper MRD negative remission.

So it's a—it's a—a test that we use to evaluate how effective a therapy is because the more patients we can achieve MRD negatives the more effective a treatment is. And so our clinical trials are—are designed to determine and—and assess MRD, the MRD negative rate in a—in a patient for—in a patient population for a particular treatment. And it's an—it's an easier way to assess the effectiveness without having to treat patients and do all the follow up—long-term follow up to see long they stay in remission. Because it's really correlated with how long patients stay in remission, and how long their survival—their anticipated survival is. 

 

Esther Schorr:            

That's very helpful. Thank you. I just have one other question, can you comment on—are there now bigger—big differences between first line and second line or additional treatments, and—you know, because you're talking about combination therapies especially. How does—how does that landscape look?

Dr. Wierda:                

Right. So, there—there's a lot of—I don't know that I would say controversy, but there's – there are different approaches the clinicians can take in terms of treating patients with their first treatment. What we refer to as first line treatment, is the first treatment a patient experiences, or is exposed to. First line treatment can be with chemotherapy-based treatment. It can be with Ibrutinib or BTK inhibitor based treatment, or it can be with Venetoclax or Bcl-2 directed treatment. Those are three categories of standard first line therapy.

And if you talk to a hundred or ten CLL experts you'll get a variety of recommendations and justification to support those recommendations. And they're all based on data that we have currently available. There's a lot opinion and a lot of differing opinions these days and you'll see that also in the community.

There have been recent trials that have shown improved remission duration with BTK inhibitor based therapy, like ibrutinib. So a patient—compared to chemotherapy, patients have a better, longer disease control and remission if they're treated with ibrutinib based therapy first compared to chemotherapy.

Now, the challenge with that is that ibrutinib-based therapy is continuous treatment until it doesn't work any longer. That's usually for many years with ibrutinib because ibrutinib is so effective, and active. And everything has side effects and toxicities associated with it, so in a strategy like that where patients go on treatment that's indefinite we worry about side effects and toxicities and long-term effects compared with chemotherapy where you're giving patients six months of treatment and the treatments stops and they go in remission.

So there are different strategies that people are proponents of these days. There is some controversy in terms of, you know, what's the best strategy for a particular patient, particular patient population. And also in terms of what patients should get after they've had their first treatment. So their—their first treatment—their second treatment, or treatment for relapse disease will be dictated by what they get as their first treatment. For example, if they get chemotherapy first, then if the disease is in remission for a while and it comes back and it needs to be retreated we wouldn't necessarily go back to chemotherapy. We would move to BTK inhibitor based therapy or ibrutinib-based therapy.

So it's—it's really a time, I think, that's very important for patients to understand what their treatment options are. It's an important time to have a good discussion with their doctor about the pluses and minuses of each strategy. It's important for patients to ask their physician why they are recommending a particular treatment over another and to have an understanding of, you know, what's—what's the importance for that selection for a particular patient and what they can expect with selecting that treatment option for them. 

And how that may affect what they're going to get if the disease returns or needs to be—their treatment needs to be switched. So it's a very important topic right now in terms of having the dialog with the physician and having a good understanding from your physician about what's important in their minds about their recommendation for the patients.

Esther Schorr:            

Okay. That's great information, Dr. Wierda, thank you so much. So, in sum, it sounds like there are more choices than ever for patients, and a lot of hope. Have I read that correctly?

Dr. Wierda:                

There has never been a time that there has been more hope and more optimism in my mind, and I think in most of us who work in CLL, than now. We have many options. We have many options that work if something else doesn't work. And we have many—many—many good ways to control the disease. And I'm optimistic that we'll be able to use those treatments and combine them and—to develop curative therapies. I think we're very close to having a cure for many patients with CLL. And it's a very optimistic time and we need to continue our—our—our work.

We need to encourage patients to think about clinical trial options, because the only way we're going to make progress is if we are able to test new things and develop new treatments and we can only do that with a clinical trial. So there's no progress in treatment without clinical trials. And I applaud those patients who participate on clinical trials for their courage. But it's never been a more optimistic time for us—for me particular, in terms of potentially curative strategies and—and working on developing those for our patients.

Esther Schorr:            

Wow. That is definitely a message of hope. Well, Dr. Wierda, thank you so much, as usual it's just a delight to talk to you and your message of hope and choice and all of that is really encouraging for all of us.

This is Esther Schorr from La Jolla, California, for Patient Power. And remember knowledge can be the best medicine of all.

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.