The Promise of Second-Generation CLL Treatments

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Topics include: Treatments

Which second-generation investigational CLL treatments are showing promise? Dr. Philip Thompson, a CLL expert from MD Anderson Cancer Center, shares an update about novel treatments and emerging combination approaches.

This program was developed in collaboration with and sponsored by CLL Global Research Foundation which received support from AbbVie Inc., Genentech and Biogen Idec. 

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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:

Hello and welcome to Patient Power. I’m Andrew Schorr at Stanford University Medical Center in San Francisco. While I’m here, there is a meeting called the iwCLL going on in Sydney, Australia. Our correspondent on the scene is Dr. Philip Thompson, a CLL expert from MD Anderson Cancer Center in Houston. Welcome to Patient Power, Dr. Thompson. 

Dr. Thompson:                  

My pleasure.

Andrew Schorr:                  

So, Dr. Thompson, what’s the promise of second-generation investigational medicines?

Dr. Thompson:  

I think the most exciting drug in this area is venetoclax, or previously known as ABT-199.

So John Seymour from Peter MacCallum Cancer Center in Australia presented updated data from the single agent venetoclax study.  This is a medication that blocks a protein in the CLL cells that is essential for the CLL cells to survive.  And when you block this protein, the CLL cells die rapidly.  The first patient that received this medication actually developed a complication called tumor lysis syndrome, which occurs when all of the CLL cells die so rapidly that the internal contents of the cells are released into the bloodstream and can cause problems with the kidneys.  And as a result, the medication now has to be given very carefully for the first four weeks.  It’s started at 1/20th of the target dose and then gradually increased over four weeks.

However, once the target dose—and by doing this, the risk of tumor lysis syndrome is essentially ameliorated almost completely.  Very few cases of significant tumor lysis syndrome have been seen since we’ve been doing it this way.  And other than that, the medication is almost free of side effects other than a small proportion of patients who develop a low neutrophil count or neutropenia.

So there appear to be very few long term what we call off-target side effects.  So for example, ibrutinib (Imbruvica) has the atrial fibrillation and the bleeding; we’re not seeing side effects like that with venetoclax.  The other thing that’s very exciting about venetoclax is that it achieves very, very what we call deep remission.

So patients are achieving high rates of complete remission, and they’re achieving high rates of minimal residual disease; negative complete remission, even with a single drug. 

And it was also discussed at the iwCLL meeting—and some of these results had also been previously presented at the European Hematology Association meeting in June—that when combined with rituximab (Rituxan), the rates of complete remissions and the rates of minimal residual disease negativity approximately double.  So almost 50 percent of patients with relapsed CLL were achieving minimal residual disease negative complete remission with venetoclax plus rituximab.

So these are very, very exciting results.  And this drug, given its mechanism of action, lends itself perfectly to being used in combination with other novel therapies such as ibrutinib and also potentially with some of the older therapies like chemotherapy.  But it’s being pursued by a number of groups in studies with ibrutinib, and I think that’s going to be the next big thing in CLL.

Some of the other second-generation investigational medicines you may have heard of include duvelisib, which was previously known as IPI-145.  This drug is an inhibitor of (PI) 3-kinase gamma and (PI) 3-kinase delta.  So it’s similar to idelalisib or Zydelig.  It is very potent, so Dr. Susan O’Brien from UC Irvine presented some data at iwCLL showing that patients who’ve had a lot of prior treatment have very, very good responses to this medication, including patients with 17p deletion, although these represented quite a small—also including even—there were six patients who had previously received the ibrutinib and one of those patients responded.

But there were approximately half the patients who had 17p deletion on the study, and they were having excellent responses to the medication.  As part of the meeting, one of the interesting things about the iwCLL meetings is a lot of scientific data is presented where we can see how, in the laboratory—sometimes in mouse models, sometimes in other types of laboratory tests—which medications are likely to work together.

And there were some beautiful data presented by Matt Davids from the Dana Farber Cancer Institute suggesting that interesting will work very well with venetoclax, and also data presented by Varsha Ghandi from the MD Anderson, who showed that duvelisib looks like it will be very potent in combination with venetoclax.

And so I would expect both of these combinations to move forward in clinical studies.  As I mentioned, ibrutinib plus venetoclax is already being studied in a number of centers, and we’re likely to have a study at MD Anderson in the not-too-distant future.

Andrew Schorr:              

Dr. Philip Thompson, CLL specialist from MD Anderson Cancer Center, thank you for joining us from the iwCLL meeting in Sydney, Australia to bring us the latest news. For our audience, be sure to join the Patient Power Community so that you can be informed whenever we post something new. I’m Andrew Schorr. Remember, 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 October 13, 2015