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Are Therapies Being Developed to Target Specific Mutations in CLL?

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Published on April 10, 2019

After identifying genetic mutations in chronic lymphocytic leukemia (CLL) patients, how is the information used to form a treatment plan? Will therapies target specific mutations? Leading CLL expert Dr. Jennifer Brown, from Dana-Farber Cancer Institute, gives insight to where research is today on targeted therapies for CLL and mutations currently in clinical studies. Watch now to find out more.

Provided by CLL Global Research Foundation, which received support from AbbVie Inc., Gilead Sciences and TG Therapeutics.

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Transcript | Are Therapies Being Developed to Target Specific Mutations in 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.

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, Dr. Brown you were discussing these genes that are identified, and it’s sort of a moving target; you’re still trying to, in some of the cases, know what’s significant. Now, we’ve seen that in lung cancer, and a number of other areas where we didn’t know a year or two years ago, and then, we say, “Wow, we do know” and there’s a medicine maybe that’s even been developed to help go after that cancer gene. So, talk about that a little bit, where we’re headed, as you identify some of these other genes. You were muted. There you go.

Dr. Brown:                             

That’s a very interesting question in CLL. As I mentioned earlier, we don’t have any single mutation that turns up in a large percentage of patients. And we actually have a few that occur in 10 to 15 percent of patients, and then, a long tail of mutations that occur in only a few percent of patients each. And so far, interestingly, our drugs, like ibrutinib (Imbruvica), idelalisib (Zydelig) that work across the board, really, in CLL, work independent of these gene mutations to some extent. They target, instead, a pathway that’s active all the time, but not mutated, the B-cell receptor. 

We haven’t yet actually advanced as much with targeting specific gene mutations in CLL. Although, there’s interest in it. I, actually, have been working on targeting NOTCH 1 in the lab, and we even had a trial of that briefly. And another gene called SF3B1 is also of interest. But these aren’t easy genes to target; they’re not, for example, kinases that are overactive that you can readily inhibit. And again, they are not so common as to be widely prevalent among CLL patients.

And so, I’m not sure how much we’ll see specific targeting of particular mutations in CLL in the near term. But hopefully, we will move in that direction over time. Particularly, if we identify certain mutations where we may be able to target the mutation plus the B-cell receptor pathway together, to get deeper responses, more durable responses, reduced resistance amongst higher risk subgroups. That would be, potentially, I think, very helpful. But that’s still somewhat in its infancy.

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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