What Could a New Drug Approval Mean for CLL Patients?

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Topics include: Treatment

Dr. William Wierda, medical director of the Department of Leukemia at the University of Texas MD Anderson Cancer Center, joins Patient Power to discuss the FDA approval of Venclexta (venetoclax) for use in CLL patients with the 17p deletion. Dr. Wierda reviews how the treatment works, its potential side effects and shares his perspective on what the approval could mean for a broader group of patients in the future. 

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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:

We have a new drug approved by the FDA, Venclexta, if I've got it right, or it was ABT-199 and venetoclax.  And joining me to help us understand it is the director of the CLL program at MD Anderson Cancer Center in Houston, that's Dr. William Wierda.  Dr. Wierda, welcome back to Patient Power. 

Dr. Wierda:

Thank you, Andrew. 

Andrew Schorr:

Okay.  So this drug was approved but not for everybody, so tell us where this drug fits in for people with CLL. 

Dr. Wierda:

Right.  So the approval with venetoclax for now is in patients who have 17p deletion and who have had a prior treatment.  And so it's a relatively restricted label that's been given so far. And that's based on the data from the 982 trial, a trial that enrolled only patients who had been previously treated and have a 17p deletion, because at the time we initiated that trial that patient population didn't have a standard of care approved for them. And the trial that was done, that enrolled over 100 patients demonstrated that there was activity with venetoclax in that population.  

Andrew Schorr:

Okay.  So for that population, is this approval a big deal? 

Dr. Wierda:

Yes, for sure, because it's a drug that's well tolerated.  We can talk a little bit about the side effects profile, and it has activity.  And we all know that the population of patients with 17p deletion are a particular challenge for us clinically, because they don't respond to chemotherapy.  Chemotherapy makes things worse for those patients.  We do have ibrutinib (Imbruvica) that has activity in that group of patients, we have idelalisib (Zydelig), and those two drugs target different molecules, and now we have a third agent that targets even a different molecule in the leukemia cells, so it's great news, I think.  

Andrew Schorr:

Okay.  Well, I know it's a powerful drug.  You alluded to side effects.  So for somebody taking this, what are the side effects. What's the monitoring that has to happen to make sure it's used safely?  

Dr. Wierda:

So there [are] really two side effects that we see with the medication—major side effects that we see with the medication.  One is what's referred to as tumor lysis syndrome, and the other is neutropenia. And so we'll talk about each of those briefly, because they're very different. 

Tumor lysis is something that happens when leukemia cells die very rapidly, and they release toxins essentially to the blood that the kidneys have difficulty clearing and can't really keep up.  So when we did the initial Phase I trial we learned that if patients started at too high of a dose or if they escalated their dose too rapidly, they ran into problems with tumor lysis. 

So the way that this is mitigated now is by starting at a low dose of 20 milligrams a day and staying on that dose for a week and then escalating to 50 milligrams daily for a week, then 100 milligrams daily for a week, 200 milligrams daily for a week, and then up to the target dose, which is 400 milligrams daily dose.  And there's monitoring during those—each of those steps when you escalate the dose where labs are checked.  They're checked prior to the escalating dose and then several hours after the escalating dose to make sure that things are clearing, kidneys are able to keep up with those dying leukemia cells and releasing or eliminating the bad stuff that's released into the blood. 

Patients are also prescribed hydration, so they may drink fluids when they initiate on treatment and then with each of their dose escalations.  And then there's a strategy where we can stratify them into patients who are at greatest risk for that toxicity, tumor lysis, and that's based on how much leukemia they have present in their body at the time when they start on treatment.  So there [are] a lot of measures that we're doing to ensure safety.  I think it's a critical issue because, as you mentioned, it's a very potent drug.  It's a very active drug, very effective drug, and we just need to be very cautious at this initial—at the initiation of treatment and then this initial escalation of the dose so that we can get patients safely started on their treatment. 

Once they get up to that target dose, there [are] really no major safety concerns like there are with the dose escalation.  As I mentioned, neutropenia can occur, and that is managed with growth factor, and sometimes we reduce the dose if we have persistent neutropenia.  

Andrew Schorr:

Okay.  And then that's where you have low neutrophils and might be of at risk of infection. 

Dr. Wierda:

Correct.  

Andrew Schorr:

Okay.  And so people need to have had genetic testing to know are they 17p deleted, right?  Hopefully that's typical now, hopefully for more people with CLL.  I hope so. 

Dr. Wierda:

I don't know if it's typical.  I think it's important for patients to remind their providers that at any time they could—it happens particularly after they have had a treatment they can develop a 17p deletion. So when a patient switches treatment or needs a new treatment, that's the time to check and recheck whether or not 17p is present.  I think some providers do forget that at that point in time, so it's important to raise that to their physician.  

Andrew Schorr:

And the FDA has approved it if you have had previous treatment.  Does it matter which treatment you have had?  

Dr. Wierda:

It's not restricted to the prior treatment, no.  

Andrew Schorr:

Okay.  So we have drugs for people with a wider variety now of CLL, and you have more agents. So for you helping run the leukemia program there and the CLL program at MD Anderson, how do you feel about the FDA approving this where you can gain more experience with it, and you have a specific population that it can benefit right now? 

Dr. Wierda:

I think it's great news for patients with 17p for now, and, as I mentioned, it's a very potent, it's a very effective drug.  It doesn't have the long?term toxicity that chemotherapy has, and I see in the future expanding its use to previously treated patients and potentially patients in the frontline setting.  I feel that this drug is another opportunity for us to enter and move into the era of chemo?free treatment, potentially curative treatment for patients of CLL.  

Andrew Schorr:

Okay.  Well, as my mother used to say, from your lips to God's ear. And we really hope that when anybody starts talking about the word cure that we can really get there, but certainly a great step forward now and available for a wider, wider group of patients around the country with the FDA approval.  Dr. William Wierda from MD Anderson Cancer Center, thank you for being with us once again. 

Dr. Wierda:

Thank you, Andrew.  

Andrew Schorr:

Okay.  I'm Andrew Schorr in San Diego, Dr. Wierda in Houston, reminding you that knowledge can be the best medicine of all. 

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 April 25, 2016