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CLL: Practical Advice on Selecting and Managing Therapy

Panelists: Ian W. Flinn, MD, PhD, Sarah Cannon Research Institute; Matthew S. Davids, MD, MMSc, Center for Chronic Lymphocytic Leukemia at Dana-Farber Cancer Institute; Brad Kahl, MD, Washington University School of Medicine; John Pagel, MD, PhD, Swedish Cancer Institute
Published: Wednesday, Aug 07, 2019



Transcript: 

Ian W. Flinn, MD, PhD: Brad, there are a couple of data sets that are going to read out soon, including the one we just talked about in the study comparing it to chemotherapy. Let’s say acalabrutinib gets approved for CLL [chronic lymphocytic leukemia]. What are your thoughts? How are you going to use it? Are you going to switch everyone over to acalabrutinib? Is it going to be your drug of choice? Are you going to stick with ibrutinib? What do you think?

Brad Kahl, MD: My experience with acalabrutinib has been similar to that of the other panelists. I often find it to be a little better-tolerated than ibrutinib for some of these nagging chronic toxicities. The hypertension with ibrutinib can be a problem, as well as the bleeding, myalgias, and arthralgias. Assuming acalabrutinib does get an indication in CLL, I could easily see it being my preferred BTK [Bruton tyrosine kinase] inhibitor.


Ian W. Flinn, MD, PhD: We’re going to move on to yet another BTK inhibitor—zanubrutinib. It used to be BGB-3111. There are a variety of data sets that have been presented. What is the advantage? Is this just another BTK inhibitor?

John Pagel, MD, PhD: Time will tell. I think it’s another valuable drug. It’s important to have another tool that we can use. It makes things a little bit more confusing, perhaps, because it’s not clear where it differentiates itself at this point. Part of the problem we have with zanubrutinib to this point is that we don’t have a lot of experience with it in the United States. It was tested almost completely outside the United States. We need to gain a lot more experience with it. The good thing is that there is a randomized trial, direct head-to-head versus ibrutinib in CLL patients. That will be very helpful for understanding the differences there. It will tell us about the differences compared with acalabrutinib. They do look to be relatively similar drugs. At the end of the day, what we’ve been talking about, which will perhaps win in the clinic, is what is most tolerable. We’re probably not curing these patients, and certainly not with single agents. We’re palliating them, and we want to keep them away from the community oncologist’s office as long as we possibly can. They want to be taking the pill and doing their normal day-to-day things.

Ian W. Flinn, MD, PhD: Matt, you have used it. You’ve treated some patients with it. Is there anything that comes to mind that differentiates it from other BTK inhibitors?

Matthew S. Davids, MD, MMSc: Based on my experience and my interpretation of the data, it seems most similar to acalabrutinib. Zanubrutinib is more selective for BTK, compared with ibrutinib, and in my experience, it does seem to be a bit better-tolerated. One of the issues with all 3 of these BTK inhibitors that we’ve talked about is that for some of these high-risk patients who become resistant, they can develop this BTK C481S mutation. That would make them resistant to any of these 3 BTK inhibitors. It’s another topic for another day, perhaps, but there’s a whole new generation of drugs that can potentially target that mutation.

Ian W. Flinn, MD, PhD: Right. You’re alluding to the non-covalently bonding drugs that are in development, which hopefully will overcome some of these mutations. Before we move on to mantle cell lymphoma, are there any final thoughts on the community oncologists as they make their way through all these different treatment options? It’s hard to summarize in 1 sentence, but could you, John?

John Pagel, MD, PhD: I think the important thing is to know who you’re treating and what the comorbidities or issues around that individual patient are. That helps a community oncologist figure out what the right therapy is. It’s important to remember that venetoclax can cause tumor lysis that can be very significant. You have to know how to use that, especially in the community. You have to be familiar with that, and I would encourage any community oncologist to have a direct line of communication with a CLL expert at any point, especially when trying to figure out which of these drugs to use. A little conversation there would go a long way in many cases.

Transcript Edited for Clarity

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Transcript: 

Ian W. Flinn, MD, PhD: Brad, there are a couple of data sets that are going to read out soon, including the one we just talked about in the study comparing it to chemotherapy. Let’s say acalabrutinib gets approved for CLL [chronic lymphocytic leukemia]. What are your thoughts? How are you going to use it? Are you going to switch everyone over to acalabrutinib? Is it going to be your drug of choice? Are you going to stick with ibrutinib? What do you think?

Brad Kahl, MD: My experience with acalabrutinib has been similar to that of the other panelists. I often find it to be a little better-tolerated than ibrutinib for some of these nagging chronic toxicities. The hypertension with ibrutinib can be a problem, as well as the bleeding, myalgias, and arthralgias. Assuming acalabrutinib does get an indication in CLL, I could easily see it being my preferred BTK [Bruton tyrosine kinase] inhibitor.


Ian W. Flinn, MD, PhD: We’re going to move on to yet another BTK inhibitor—zanubrutinib. It used to be BGB-3111. There are a variety of data sets that have been presented. What is the advantage? Is this just another BTK inhibitor?

John Pagel, MD, PhD: Time will tell. I think it’s another valuable drug. It’s important to have another tool that we can use. It makes things a little bit more confusing, perhaps, because it’s not clear where it differentiates itself at this point. Part of the problem we have with zanubrutinib to this point is that we don’t have a lot of experience with it in the United States. It was tested almost completely outside the United States. We need to gain a lot more experience with it. The good thing is that there is a randomized trial, direct head-to-head versus ibrutinib in CLL patients. That will be very helpful for understanding the differences there. It will tell us about the differences compared with acalabrutinib. They do look to be relatively similar drugs. At the end of the day, what we’ve been talking about, which will perhaps win in the clinic, is what is most tolerable. We’re probably not curing these patients, and certainly not with single agents. We’re palliating them, and we want to keep them away from the community oncologist’s office as long as we possibly can. They want to be taking the pill and doing their normal day-to-day things.

Ian W. Flinn, MD, PhD: Matt, you have used it. You’ve treated some patients with it. Is there anything that comes to mind that differentiates it from other BTK inhibitors?

Matthew S. Davids, MD, MMSc: Based on my experience and my interpretation of the data, it seems most similar to acalabrutinib. Zanubrutinib is more selective for BTK, compared with ibrutinib, and in my experience, it does seem to be a bit better-tolerated. One of the issues with all 3 of these BTK inhibitors that we’ve talked about is that for some of these high-risk patients who become resistant, they can develop this BTK C481S mutation. That would make them resistant to any of these 3 BTK inhibitors. It’s another topic for another day, perhaps, but there’s a whole new generation of drugs that can potentially target that mutation.

Ian W. Flinn, MD, PhD: Right. You’re alluding to the non-covalently bonding drugs that are in development, which hopefully will overcome some of these mutations. Before we move on to mantle cell lymphoma, are there any final thoughts on the community oncologists as they make their way through all these different treatment options? It’s hard to summarize in 1 sentence, but could you, John?

John Pagel, MD, PhD: I think the important thing is to know who you’re treating and what the comorbidities or issues around that individual patient are. That helps a community oncologist figure out what the right therapy is. It’s important to remember that venetoclax can cause tumor lysis that can be very significant. You have to know how to use that, especially in the community. You have to be familiar with that, and I would encourage any community oncologist to have a direct line of communication with a CLL expert at any point, especially when trying to figure out which of these drugs to use. A little conversation there would go a long way in many cases.

Transcript Edited for Clarity
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