Published on March 20, 2017
Why isn’t venetoclax (Venclexta) approved as a front-line therapy for CLL? Dr. Nicole Lamanna of Columbia University Medical Center and Dr. Michael Keating of MD Anderson Cancer Center explain the mechanism behind venetoclax, offering insight into the behavior of this therapy and explaining the need for continued clinical trials.
Provided by CLL Global Research Foundation, which received support from AbbVie Inc., Genentech Inc., Gilead Sciences, Pharmacyclics, Inc., Teva Pharmaceuticals and TG Therapeutics. In partnership with The University of Texas MD Anderson Cancer Center.
Transcript | How Does Venetoclax Work to Treat CLL?
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So how does Venclexta work or venetoclax, Nicole? We talked about BTK. So how does this work?
So the CLL and lymphoma cells are overexpressed on another protein called BCL2. And so this inhibits that. So it’s different than the signaling pathway that Dr. Keating was referring to, but it’s overexpressed in both CLL patients and lymphoma cells, and this inhibits that particular protein.
I think one of the things is that the BCL2 is sort of survival protein it was thought to be an immortalizing protein that the cells live forever
Because the normal B cell will die off in about a week, but the CLL cells live on average about 100 days. So if venetoclax complex with the BCL2, there’s no survival signal. The cells fall apart. Sometimes they fall apart too quickly so that you have to really watch out that you’re not suffering from this tumor lysis syndrome that can occur when there’s an exuberant death of the cells.
And your body can’t keep up.
And then just to add to that, what’s important about the survival signals is what’s complicated about CLL, of course, is that as we’re targeting these various proteins and things as we learn about the biology, clearly it’s more complicated. Because there are other things that keep these CLL cells alive, and that’s what we’re all trying to strive to achieve and looking at combinations and different ways to attack the CLL cells or what’s supporting the CLL cells. So as we talk about, so this is approved in relapsed and in patients with 17p deletion.
It’s not yet approved in front-line therapy.
Right. But there are clinical trials going on. I alluded to the trials with venetoclax and Gazyva, obinutuzumab. That’s been going on. I know one lady from Australia who’s actually doing very well with that. So but again, they’re trying to answer scientific questions, which combinations that we’ll talk more about can work for which person and what are the features, you’ve talked about, 17p, 11Q, et cetera, who does it work for. And the FDA, for instance, has approved venetoclax for people with that 17p deletion, but they’re looking at it for wider populations. Okay.