An Update on Second-Generation Inhibitors for CLL

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Topics include: Treatments

On-site in San Diego, at the 2018 American Society of Hematology (ASH) annual meeting, chronic lymphocytic leukemia (CLL) experts Dr. Susan O’Brien, from the University of California Irvine Medical Center,and Dr. Javier Pinilla, from the H. Lee Moffitt Cancer Center & Research Institute, joined Patient Power toshare exciting developments in ongoing treatment research on a new class of inhibitors for chronic lymphocytic leukemia (CLL). The panel discusses efficacy of the treatments under investigation, potential side effects and when it’s appropriate for CLL patients to use them. Watch now to hear the latest news.

Sponsored by Pharmacyclics.

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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.

Andrew Schorr:                     

So, that’s a BTK inhibitor. And then, you have others in this PI3…

Dr. Pinilla:                  

…a delta.

Andrew Schorr:          

What about that class? There are other drugs in development there. Where will they come in? Because I know idelalisib (Zydelig) was not a home run. And when we poll people, a lot of people using Ibrutinib, but far fewer on that. So, will a second generation make a difference?

Dr. O’Brien:                

Well, there was a second generation drug that just got approved in CLL. That’s called duvelisib (Copiktra).

Andrew Schorr:          

Right.

Dr. O’Brien:                

It’s a little bit different than idelalisib because it inhibits PI3K Delta, as you said, but it also inhibits the gamma isoform. Is that important for the activity or the safety? Not totally clear. We know that the activity of idelalisib was quite good. But as you alluded to, it was the safety profile that caused some problems. There is some rational because of the gamma inhibition that this drug has, duvelisib, that it may cause less toxicity. The type of toxicities, elevation in liver function tests, which is not a big deal because it doesn’t make people uncomfortable. The patients are not complaining. 

We just need to monitor it. Or pneumonitis, just inflammation in the lung, which is rare but happens, or colitis which is sort of like bad diarrhea. 

Those can occur with duvelisib. But the incidents appears to be decreased in what we see with odelalisib. And the one caveat to that is the experience, of course, since it’s a brand new drug, with duvelisib is much more limited. So, our confidence in that is just based on smaller numbers. But that drug is now available and could be used in any relapsed patient with CLL. 

Andrew Schorr:          

And then, others in the class in investigation, I think, is it umbralisib? 

Dr. Pinilla:                  

Yes. In fact, Umbralisib is the third drug that’s coming as Susan was describing very well. And duvelisib may really have a similar side effect. It’s unclear. It’s going to be better tolerating in the long term because it’s unlikely, in the future, we’re going to have randomized trials. Umbralisib is a similar example. And however, it seems that the safety profile is quite favorable.

At least, when we see the data, we don’t really see as many side effects that we have seen with the other two. Once again, the clinical trials are ongoing, and we need to wait for the final results and to really see that, obviously, it’s a period of other things. But definitely, at the end of the day, it’s something that we need to wait for.

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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Page last updated on March 20, 2019