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Remission in CLL Through Combination Therapies

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Published on July 22, 2020

Can CLL Patients Achieve Remission Through Combination Therapies?

Researchers are finding that by combining current treatments for chronic lymphocytic leukemia, patients can achieve deep remission and spend less time on CLL drugs. Most patients are able to stop treatments after two years. Dr. Nitin Jain, Associate Professor, Department of Leukemia, Division of Cancer Medicine, and Patient Power co-founder and CLL patient, Andrew Schorr discuss the potential of combining two and even three treatments to achieve better health outcomes for patients.

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Transcript | Remission in CLL Through Combination Therapies

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, and welcome to Patient Power. I'm Andrew Schorr. Living with chronic lymphocytic leukemia for 24 years when I was initially treated, three drugs, the FCR regimen in a clinical trial worked for a long time going after the cancer in different ways. Yet in recent years, some people are just getting one pill, ibrutinib (Imbruvica) or maybe now they're getting acalabrutinib (Calquence) and there are others coming. So what about combination therapy now? So with us is Dr. Nitin Jain from MD Anderson Cancer Center, a CLL specialist there. Dr. Jain, so often we thought in cancer and certainly in some other conditions like multiple myeloma, they have four drug combinations. Where are we now with more than the single drug, using two or three, or maybe there could be more? Combinations. Where are we now with that?

Dr. Nitin Jain:

Yeah, so I think the CLL landscape has changed quite remarkably. So as you mentioned, when you got it, FCR was the standard of care. And I think for a select group of patients, it can still be considered a standard of care. But in large part, I think patients are these days receiving newer targeted therapies. So just to kind of…for a newly diagnosed patients who need treatment, we have ibrutinib, which can be given just by itself, a pill that you take a, every day. Acalabrutinib is a more recent edition. Similar to ibrutinib, it targets the same pathway, and it can be given once a day. It is given twice a day actually, but needs to be taken indefinitely. And then we venetoclax (Venclexta), which is a pill again, given once a day. And it's typically combined with an antibody obinutuzimab (Gazyva) for six months and venetoclax is given for one year.

So those are the three, I would say, FDA approved regimens with target therapies, for patients who have no prior therapy and their doctor is recommending first time therapy for their disease. But one of the things which our group and other investigators in the field have been working on are trying to combine these drugs together to find maybe an optimal regimen, which can be given not for lifelong, but for a well-defined period of time. And then to maximize the chance that the patients get deep remission and then to be able to stop therapy. So our group led work, combining ibrutinib plus venetoclax together. So the two oral drugs together, there is no antibody in that regimen. And that's a regimen which we, and now others and many other groups will also be pursuing the same regimen, which we have shown that it leads to deep remission for our patients.

And the patients are able to stop therapy. Most patients are able to stop therapy, I should say at two year mark. So it's not given indefinitely. At two years, majority of the patients are able to stop the therapy. Similarly, other groups have shown that even one year of therapy may be sufficient and those trials are ongoing again, combining ibrutinib with venetoclax. And then there is other kind of... You can swap the ibrutinib for acalabrutinib. So investigators are doing acalabrutinib combined with venetoclax plus obinutuzumab. Investigators are using zanubrutinib (Brukinsa), which is another new oral BTK inhibitor, like ibrutinib. And they're combining that with venetoclax plus obinutuzumab. There are other regiments which are being brought up again, combining these kinds of drugs together in different ways and for different duration of therapy. So all those I would say right now are in clinical trials. Nothing is approved yet by the FDA, but in the United States and elsewhere, a lot of trials are happening where different combinations are being pursued.

So I think in the next two or three years, we'll have... And again, as the data matures, this will be presented at medical meetings and publications, but I think we'll learn more. Whether you can do better by these doublet or triplet combination compared to what we already know, you can do great with ibrutinib, acalabrutinib, and venetoclax. All these drugs, you can already do great, but can you make them even better? Can you make them the duration of drugs to be given shorter, which I think would help everyone in terms of time-limited therapy. So I think that's a big excitement in the field and I see a lot of researchers, myself, our group here, and many other groups are working in developing what is called time-limited therapy. So give the drugs for one to two years and then be able to stop the drugs. Then you enter what is called a treatment free remission period. And then hopefully that will last for years and years to come. But that's something we don't know that right now, because most of these trials have been started just in the last few years.

Andrew Schorr:

Wow. Well, I have a personal perspective on it. So I was at MD Anderson, the phase II trial for FCR, and I had a 17 year remission. So I had six months of therapy and then nothing for many, many years. So I'm a big believer in, can you do the therapy and stop and go on with your life? The other thing that comes into play of course now is cost. And here in our American system, as well, particularly with the oral therapies, people have copays, depending upon their insurance and their situation, or if they have insurance. So there's a lot that comes into place. So I think if we can move more towards fixed duration, like I got the benefit of, I think that's, as you said, fixed duration or time limited as you said that is definitely favorable, if it can be effective.

So thank you so much for explaining where the research is headed. We'll get updates from you in the future. But I think for those of us with CLL who need treatment now, may need treatment in the future, these questions are being asked, are two drugs or even three drugs better than one, and can it get you to a point where you can stop and just go on with your life? Dr. Nitin Jain, thank you so much for being with us from MD Anderson.

Dr. Nitin Jain:

Thank you everyone. Thank you, Andrew.

Andrew Schorr:

Okay. Andrew Schorr here. 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.

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