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BTK Inhibitors in Chronic Lymphocytic Leukemia

Insights From: Brad S. Kahl, MD, Washington University School of Medicine; Steven P. Treon, MD, PhD, Harvard Medical School
Published: Wednesday, Apr 03, 2019



Transcript: 

Brad S. Kahl, MD: There were some updates on some data for zanubrutinib in relapsed CLL [chronic lymphocytic leukemia]. This was updated at the Lugano meeting [the 15th International Conference on Malignant Lymphoma]. This was a big study in CLL, with a few hundred patients. It’s clear that zanubrutinib is very active in CLL, with high response rates—over 90%. Like with other BTK [Bruton tyrosine kinase] inhibitors, most of those responses are partial remissions. The safety and adverse-event profile looked very reasonable. It was pretty comparable to other BTK inhibitors. It’s hard to tell right now whether it’s better or worse or just the same. But I think the point here is that we’re going to have large data sets for zanubrutinib in relapsed CLL relatively soon in publication. Then we’ll really be able to look at that data and make a determination whether this new BTK inhibitor offers any advantages over what we already have.

I think it’s possible that zanubrutinib could receive approvals for use in chronic lymphocytic leukemia at some point. There’s a large, frontline study that’s currently being conducted, a global study, comparing zanubrutinib against standard BR [bendamustine and rituximab] therapy. If zanubrutinib performs well in that study, it could get a frontline indication in CLL.

There are also some large relapsed and refractory experiences going on around the world. It could also get an indication in those settings. If it does get FDA indications, then the decision for clinicians is going to be which BTK inhibitor to use. “Do I use ibrutinib?” “Do I use acalabrutinib,” assuming acalabrutinib gets an approval in CLL? Or, “Do I use zanubrutinib,” assuming zanubrutinib gets an approval? At this point, I’m not prepared to say which one is going to be used more often. I think it will depend on the specific FDA indications. I think it will depend on a closer look at the safety profiles—the adverse-effect profiles.

Even now, there could start to be some pricing issues. These are oral drugs. They’re very expensive, and sometimes there are significant out-of-pocket expenses for patients—large co-pays. So if you’re a clinician like me who’s in the trenches treating patients all the time and you’re dealing with this in your clinic, where you’d like to start a patient on a BTK inhibitor but they have a huge problem affording the medicine, it would be great if we got some price competition in the field to help drive the cost of these drugs down. A lot of us would really like to see these drugs become more affordable for our patients.

We did get an update on acalabrutinib used as initial treatment in CLL at the ASH [American Society of Hematology] meeting this year. It was a frontline trial with almost 100 patients, and the activity is remarkable in the frontline setting. The response rate was 97%. At 3 years, the duration of remission was over 95%. Very few patients had to come off for toxicity or adverse events.

As with all BTK inhibitors, there are some toxicities that patients experience, such as some degree of headache, which is an adverse effect for acalabrutinib. You don’t see as much with ibrutinib. You also see diarrhea, arthralgias, myalgias, bleeding. But when BTK inhibitors are used as initial treatment in CLL, the activity is remarkable. The ability to control the disease is truly remarkable, and over 90% of patients will still be on therapy in remission out 2 or 3 years when they start BTK inhibition as their initial form of therapy.

Transcript Edited for Clarity
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Transcript: 

Brad S. Kahl, MD: There were some updates on some data for zanubrutinib in relapsed CLL [chronic lymphocytic leukemia]. This was updated at the Lugano meeting [the 15th International Conference on Malignant Lymphoma]. This was a big study in CLL, with a few hundred patients. It’s clear that zanubrutinib is very active in CLL, with high response rates—over 90%. Like with other BTK [Bruton tyrosine kinase] inhibitors, most of those responses are partial remissions. The safety and adverse-event profile looked very reasonable. It was pretty comparable to other BTK inhibitors. It’s hard to tell right now whether it’s better or worse or just the same. But I think the point here is that we’re going to have large data sets for zanubrutinib in relapsed CLL relatively soon in publication. Then we’ll really be able to look at that data and make a determination whether this new BTK inhibitor offers any advantages over what we already have.

I think it’s possible that zanubrutinib could receive approvals for use in chronic lymphocytic leukemia at some point. There’s a large, frontline study that’s currently being conducted, a global study, comparing zanubrutinib against standard BR [bendamustine and rituximab] therapy. If zanubrutinib performs well in that study, it could get a frontline indication in CLL.

There are also some large relapsed and refractory experiences going on around the world. It could also get an indication in those settings. If it does get FDA indications, then the decision for clinicians is going to be which BTK inhibitor to use. “Do I use ibrutinib?” “Do I use acalabrutinib,” assuming acalabrutinib gets an approval in CLL? Or, “Do I use zanubrutinib,” assuming zanubrutinib gets an approval? At this point, I’m not prepared to say which one is going to be used more often. I think it will depend on the specific FDA indications. I think it will depend on a closer look at the safety profiles—the adverse-effect profiles.

Even now, there could start to be some pricing issues. These are oral drugs. They’re very expensive, and sometimes there are significant out-of-pocket expenses for patients—large co-pays. So if you’re a clinician like me who’s in the trenches treating patients all the time and you’re dealing with this in your clinic, where you’d like to start a patient on a BTK inhibitor but they have a huge problem affording the medicine, it would be great if we got some price competition in the field to help drive the cost of these drugs down. A lot of us would really like to see these drugs become more affordable for our patients.

We did get an update on acalabrutinib used as initial treatment in CLL at the ASH [American Society of Hematology] meeting this year. It was a frontline trial with almost 100 patients, and the activity is remarkable in the frontline setting. The response rate was 97%. At 3 years, the duration of remission was over 95%. Very few patients had to come off for toxicity or adverse events.

As with all BTK inhibitors, there are some toxicities that patients experience, such as some degree of headache, which is an adverse effect for acalabrutinib. You don’t see as much with ibrutinib. You also see diarrhea, arthralgias, myalgias, bleeding. But when BTK inhibitors are used as initial treatment in CLL, the activity is remarkable. The ability to control the disease is truly remarkable, and over 90% of patients will still be on therapy in remission out 2 or 3 years when they start BTK inhibition as their initial form of therapy.

Transcript Edited for Clarity
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