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Oral Treatment Regimens and Response for CLL

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Published on January 23, 2020

Key Takeaways

  • MRD testing is important, but it’s not the only thing to consider in CLL patients.
  • Understanding the biology of each patient’s disease has a huge influence on remission.
  • There are other oral therapies coming along, but we are still learning about the durability of remission if a patient stops oral CLL therapy. 

Chronic lymphocytic leukemia expert Dr. Philip Thompson, from The University of Texas MD Anderson Cancer Center, discusses types of oral treatments for CLL, and factors that determine whether patients can be on a fixed duration versus indefinite therapy regimen. Dr. Thompson also explains how disease biology can influence remission duration, and what MRD status means for patients.

This program is sponsored by AbbVie Inc., Genentech, Inc. and Adaptive Biotechnologies. These organizations have no editorial control. It is produced by Patient Power and Patient Power is solely responsible for program content.

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Transcript | Oral Treatment Regimens and Response for CLL

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:            

In terms of measuring success for treatment…people are placing a lot of hope that they won’t have to be on the oral meds forever, how realistic is that? 

Dr. Thompson:           

Well, the answer is it depends which oral medication you’re on. So that’s the first thing I would say. Now, so MRD testing is important in certain situations, but it’s not important in others. So, for example, I think ultimately, the best measure of success is the patient is alive, and the patient has a good quality of life, and you can get there in different ways. So, you know we now have kind of two different types of very potent oral therapy that can control CLL, one is Bruton tyrosine kinase inhibitor, ibrutinib (Imbruvica) is the one that’s currently approved, and there will be others coming along like acalabrutinib (Calquence). Ibrutinib controls the disease extremely effectively, but it doesn’t eradicate the disease in the vast majority of patients. And so, as Dr. Awan was mentioning, you have to take this drug indefinitely.

But I have patients who have been on ibrutinib for eight years, and they’re continuing to tolerate the treatment, they have no side effects, they have an excellent quality of life. If I do MRD testing, I find they have 1 percent CLL, but if this is causing no symptoms, they have a fantastic quality of life, is this a major problem? So, the answer is, well, in that situation, MRD testing is not helpful. There’s a different treatment paradigm which comes from the drug venetoclax (Venclexta), which you’ve probably heard of. So, venetoclax has a different target to Ibrutinib; it targets a protein that prevents the CLL cells from dying, so when you block this protein, they die off rapidly; particularly when you combine it with an antibody-like rituximab (Rituxan) or veltuzumab you can get what we call very deep remissions.

 So, when we look in the bladder, we look in the bone marrow, and we do a special test called flow cytometry, which can detect one CLL cell out of 10,000 normal cells; there’s a high chance we won’t be able to find any CLL using that test. And so, that gives us the hope that, okay, we can stop venetoclax, and maybe the patient will be a in a long-term remission without being on a daily oral therapy. What we don’t know, yet, is the durability of remission once we stop the drug. We assume this—we know from the chemotherapy era that if you are what we call MRD-negative, you’ll be in a longer remission on average than patients who are MRD-positive.

But we don’t know yet with these oral therapies like venetoclax how long are these remissions going to last? So, we can tell that when we look at MRD testing again in a patient that’s been on, for example, the MURANO Study, which was venetoclax, rituximab approval of that regimen, patients who were MRD-negative had a better outcome than patients who remain MRD-positive. So, it is a useful test in that sense.

Carol Preston:            

I’m just jumping in, there are questions going around in the research in the scientific community about whether it is okay to be MRD-positive and go off some of these medications. Is it imperative that I be MRD-negative in order to stop the drug?

Dr. Thompson:           

You need to think about the disease in two ways, one is how much is there? But the second is what’s the biology of what’s there? So, there are some patients whose disease grows very quickly when they’re not on therapy, and there are other patients where the disease grows very, very, very, very slowly when they’re not on therapy. So, I’ve had some patients, for example, who’ve stopped ibrutinib therapy because of side effects, who had quite a large amount of disease when they stopped, but they haven’t actually run into any problems in several years of observation because their disease grows slowly.

So, you need to know more than just what the MRD test says; you need to understand the biology of each patient’s disease, because that will have a huge influence on the durability of remission when you’re not on a suppressive therapy.

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.

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