Is It the Era of CLL Research?

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Topics include: Treatment

There has been growing excitement around chronic lymphocytic leukemia (CLL) research over the last few years, as advances in CLL treatment and disease understanding continue to progress quickly. So why are researchers excited? One area of continued interest is the development of oral inhibitor treatments, which interrupt malignant CLL cells' ability to grow and survive. 

Dr. William Wierda, a CLL expert from MD Anderson Cancer Center in Houston, shares his thoughts about new and emerging oral inhibitor therapies that are both effective and well tolerated by patients of varying ages. Dr. Wierda explains how these treatments work in the body to fight—or inhibit—CLL and discusses why he feels more research is needed to address the potential for disease persistence and drug resistance. 

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Welcome to Patient Power, I'm Andrew Schorr. Recently, there’s been a lot of excitement, a lot of buzz about new developments in the treatment of CLL, chronic lymphocytic leukemia. What’s all the excitement about? We posed that question to Dr. William Wierda, who is a leader in research and treatment at MD Anderson Cancer Center in Houston.

It's actually been the last couple years that we've been generating data on these new small-molecule inhibitors and demonstrating the activity and the tolerability, so I think the last two or three years, and currently it would be considered the era of CLL because we have these new drugs that are going to be completely revolutionizing and changing how we manage patients with CLL.

It happened with CML several years ago with the advent of imatinib (Gleevec), which is an orally available, bioavailable small-molecule inhibitor, the BCR-Abl--BCL--BCR-Abl product. And in CLL, there has been several molecules that have been targeted for inhibition with these small molecule inhibitors, which can be taken by mouth, which have been shown to be very active and again have been shown to be very well tolerated with very, very minimal side effects profile.

Oral therapies that are very well tolerated, that don't have significant side effects and can be taken pretty much by everybody, whether you're a 60-year-old or a 90-year-old with CLL.

Andrew Schorr:

I asked Dr. Wierda what led to this new development in treatment? What’s the science behind it?

Dr. Wierda:

So I'll use first the CML example. For CML, or chronic myeloid leukemia, there's a product that's generated by the Philadelphia chromosome, which is BCR-Abl, which drives the disease. That was an easier example to target because if that was the one protein that you could say, okay, this is a very important protein for this disease, and if we develop a molecule that blocks that protein that may be a therapeutic angle, or we may have an angle that we can take as a therapeutic for that disease.

For CLL it was a little bit harder because we didn't really know what was the critical protein or what was the critical pathway to target, and so investigators in the lab went through various pathways, and it appears that the B-cell receptor pathway is an important pathway.  And so over the last several years and first in preclinical investigations, these small molecule inhibitors were developed against various key molecules in the B-cell receptor pathway signaling pathway.

And Bruton's tyrosine kinase is one of those key molecules, PI3-kinase is another, SYK is another, so there are multiple. And it's only been over the last several years that these molecules have been targeted and small molecules have been developed which block the function of those proteins, and that's sort of what has led up to where we're at right now where we have these oral agents that are active in treating the disease.

It's a little bit different because the pathway is more complicated. There are multiple proteins involved in the pathway.  There's some redundancies in the pathway, so the question arises, well, with Btk we know that it is a key molecule, so if you block that pathway, then you're shutting down most of the activity of the cells and inducing them to undergo death, the leukemia cells. But there are other redundancies in the pathway, the cells can figure out ways to bypass, and you don't necessarily kill all the cells because of this, most likely because of this

Andrew Schorr:  

I posed my next question to Dr. Wierda as an analogy: if researchers are approaching this are detectives and CLL is the criminal, does he feel like we are closer on the trail than ever before?

Dr. Wierda:

So if you use that analogy, I think we're much closer to understanding the criminal and how the criminal thinks and anticipating how to catch the criminal and how to contain the criminal, for sure.  I think there's still a lot of work that we need to do.

With the new agents that have become available, ibrutinib (Imbruvica) for example, it is going to fundamentally change how we manage CLL or it is fundamentally changing how we manage CLL, but we must realize and keep in mind that it doesn't put all patients in complete remission. And we really think, people who work in the disease and people who think about how we can make a large impact and cure the disease, ibrutinib is a step along the way. It's a step in understanding the cells, and it's certainly is an advance for treatment of the disease.

But there's still more work to do because it doesn’t eliminate all the leukemia cells.  Most of the patients who are on the drug don't achieve a complete remission.

Most of them are partial responders.  Patients have to remain on the drug in order to have containment and control of their disease, and that is an indefinite period of time.  And so we worry about things like resistance, we worry about things like persistent disease, and those of us doing research in CLL are focused right now on getting rid of whatever is left over when patients have had their best response.

Andrew Schorr:      

Thanks to Dr. William Wierda from MD Anderson for being with us once again on Patient Power. Remember, be sure to be signed up for alerts on our website, so you will know 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 May 14, 2014