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Understanding the Evolution of CLL Therapeutics

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Published on November 17, 2015

Fresh from the iwCLL conference, Dr. William Plunkett, a leading expert from MD Anderson Cancer Center, shares the latest news on CLL therapeutics with Patient Power Founder Andrew Schorr.  Dr. Plunkett is on the cutting edge of biological therapy and is encouraged by the progression of CLL treatment and research.  Learn why he feels, “The future is bright for development of…demonstrably curative CLL therapies.”

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Transcript | Understanding the Evolution of CLL Therapeutics

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.  So not so long ago there was a major meeting of people involved in research and treatment of CLL, a condition I've had for many years, the IWCLL in Sydney, Australia.  And one of the researchers who was in attendance, Dr. Bill Plunkett from MD Anderson, he's been here 40 years helping research in the leukemia area. 

Dr. Plunkett:

Yes.  

Andrew Schorr:

So about CLL and what you were discussing at that meeting, so many of us really hang on where are we now, but where could we be going next?  What seemed compelling to you?  

Dr. Plunkett:

Well, it's—the last couple of years have been quite compelling, because one of the things that seemed to be lacking in CLL therapeutics was something that was directed at the nature of the disease, the nature of the aspects of the disease we call the path of physiology that really the disease depends upon. 

So now there are a series of new agents directed at the B?cell receptor signaling pathway.  So two of those have been approved, and others that target pretty much the same targets are under development.  So the clinical results of the agents that have been approved are quite promising, and they may be moving on towards approval for frontline treatment. 

Some of the challenges are can—we already have some effective treatments with the FCR protocol, And how, if at all, would the new agents be integrated with the existing therapies that are—that have been shown to be effective? 

Andrew Schorr:

Hmm.  So I was treated with a monoclonal antibody, rituximab (Rituxan), years ago, and now I know there's another one as well, couple of others, I think.  You have those sort of infused therapies, and now we have these pills as well along the lines of what you were just discussing, new agents and maybe more coming.  So we're looking at how this works together for synergy, more power? 

Dr. Plunkett:

I think we are.  The monoclonal antibodies to which you refer I would think of as being selective because they certainly do affect—target the CLL cells, but normal lymphocytes also have the same epitope on them, so normal lymphocytes are effective as well.  So in that sense they're selective, because they don't harm T cells and other cells that are in the blood.  But certainly they're effective, and they play a nuclear role in our armamentarium against CLL. 

So trials are ongoing that have the combined antibodies with the agents that target the B?cell receptor signaling pathway.  So this is thought of as biological therapy as being opposed to and in contrast to chemotherapy, and—because they're all biologicals or targeting a biological element that the—that is involved with CLL.  

Andrew Schorr:

So combination therapy.  So might somebody then, maybe they'll get an infusion, they'll take a pill as well, and that might be sustained therapy, or is the hope that it could knock the CLL back to such a level that you could—like we've had with FCR, that you could stop therapy? 

Dr. Plunkett:

I don't think we're there yet with the B?cell signaling pathway inhibitors.  Typically, the complete response rate is not complete.  The majority of the—the far majority of the responses are partial remissions, yet it's reported that patients do quite well on this, and they are able to maintain normal lives even though they have some residual CLL cells that are detected in the blood and maybe body compartments as well, but most likely the blood. 

Andrew Schorr:

So in most cases, you think it's something where we need to keep taking these medicines to keep tamping down the CLL?  

Dr. Plunkett:

That's the way they're being administered at the present time.  One that is—the report that reports the longest duration of treatment is out over three years now, so—and that's an indication that people are continuing to take the medication daily.  It's an oral medication, so we hope that compliance will not become an issue, but then that is—that remains to be seen. 

Andrew Schorr:

Okay.  Let's talk about the role of patients.  You're very involved in often very early research, where we could go next, and trials are designed, and they say does this make sense.  So what is the role of patients today?  It seems like it's increasing as far as a dialogue with the scientists about what we're interested in, what we're willing to enroll in, what we're excited about.  It's a factor now, isn't it? 

Dr. Plunkett:

Certainly is a factor that the patients have a high level of awareness of new drug development and opportunities that are available now for treatment that weren't available five years ago. 

Directly interacting with the scientists, that really doesn't happen very often, Andrew. But rather we hear about this through our colleagues and our colleagues’ actions in terms of what they—what is chosen to develop in the clinic, what our colleagues tell us about what the patients are wanting. And really clinical investigators want the best for their patients, so—and that's the right thing to do we feel.  

Andrew Schorr:

Okay.  Well, I'm glad there's that dialogue.  So you were down in Sidney, and you're back in the lab all the time and have been doing this 40 years.  For those of us living with CLL, are you encouraged, not just where we are now but where we could be headed so that if we're living with chronic lymphocytic leukemia, we can ever better manage that? 

Dr. Plunkett:

Well, given the period of time over which I've viewed the—even from my laboratory window or my computer to understand how the therapeutics of CLL have been progressing over the last 25 years, the advances have been truly remarkable.  And I see new agents coming along not only targeting the B?cell receptor but also targeting the proteins that keep CLL alive, the antiapoptotic proteins that keep cells alive, and I think the future is really bright for the development of truly and demonstrably curative CLL therapies.  

Andrew Schorr:

Wow.  I like you using that word.  That's great.  So just to sum up then, it sounds like it's sort of a full court press, scientifically, against CLL.  One is target weaknesses on the cell to kill it, and the other is the environment that's supporting it to stay alive, pull the rug out from under it as well.  

Dr. Plunkett:

I think that those elements are clearly involved.  And make no mistake about it, the genesis of the development of those new agents comes from what we've learned in the laboratory about the biology of CLL, what is it that CLL really needs, what is it that really drives CLL, and then over a period of a decade or so these new agents have been designed, tested and largely shown to be effective to one level or another, but they're still really in their development stage even though several have been approved for—by the FDA. 

I think you know that some of the most critical or revealing research occurs post-approval by the FDA.  This is a pattern that has been seen across many cancer therapeutics. 

Andrew Schorr:

Right.  

Dr. Plunkett:

We look forward to that. 

Andrew Schorr:

Right.  So what agents do you have, and what do you continue to learn about how they can be used and combined and for whom? 

Dr. Plunkett:

Right.  

Andrew Schorr:

Okay.  Well, I think an exciting time.  You're not quite ready to retire yet, right?  

Dr. Plunkett:

No. 

Andrew Schorr:

All right.  Let's keep working towards a cure.  You used that word "curative."  I like that.  Dr. Bill Plunkett, thank you for your devotion over so many years to us, working in the lab which develops therapies that hopefully can lengthen our lives and give us a high quality of life.  Thank you. 

Dr. Plunkett:

Well, thank you very much for what you do for informing the patients and interacting with the people who are trying to help them.  

Andrew Schorr:

Thank you.  Dr. Bill Plunkett, a true star in helping us advance CLL therapy so we can live longer and live better.  

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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