CLL Research Highlights From the iwCLL 2015

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Topics include: Treatments

Each year, experts gather at the International Workshop on Chronic Lymphocytic Leukaemia–or iwCLL—to present and discuss key research findings. Dr. Philip Thompson, CLL specialist from MD Anderson Cancer Center, provides an in-depth review of the headlines from the conference. Hear Dr. Thompson’s message to patients around the world about where he feels the future of CLL research and treatment is headed.

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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:                                    

Tell us, what is the iwCLL?

Dr. Thompson:  

The iwCLL, it’s a big international meeting.  It took place in Sidney this year. For the first time it was in the Southern Hemisphere.  It goes over about three days.  There were both new data presented as well as a large educational component.  And much of the meeting seeks to kind of establish consensus among thought leaders in the field internationally and also to sort of establish, I would say, future productive research collaborations across countries, so we can move the field forward.

Andrew Schorr:                  

Dr. Thompson, as you look back on this meeting over several days, what are the headlines for you that are significant?

Dr. Thompson:  

I think the really exciting things for patients at the conference are that very much—so there was a lot of discussion at the conference about the potential for chemotherapy to be completely replaced within 10 years for most, if not all, patients.  And actually I think it’ll be replaced very shortly for most patients.

And the reason I say this is in the relapse setting, ibrutinib (Imbruvica) is having fantastic results as has idelalisib (Zydelig) with rituximab (Rituxan).  And there are a number of new therapies such as venetoclax that are also showing impressive results.  One of the big studies which was not presented at the IWCLL meeting, for which the results are actually embargoed, but there was very much a buzz on the street about the study, is the RESONATE-2 study.  This is a study that compared ibrutinib to chlorambucil (Leukeran) in patients over the age of 65.  This study is seeking to achieve registration in the United States and elsewhere for use of the ibrutinib as the first therapy for patients.

So previously patients have only been able to access ibrutinib if they have a 17p deletion or if they have received other therapy before.  The results were not presented, but there were lots of rumors going around that the results of this study are highly, highly exciting and that potentially the rate of [inaudible] in the ibrutinib-treated patients of this study is very, very, very low.

And also that the rate of survival for patients in the ibrutinib arm was 97 percent or thereabouts.  And that there’s a significant survival advantage to receiving ibrutinib first.  And why this is important is that this is something that almost certainly will lead to approval of ibrutinib as the first line of therapy in patients over 65.

So this will mean no more chemotherapy for these patients.  They will likely be able to access commercial supply of ibrutinib through their insurance.  And this will have a major impact on patients’ lives.  My personal experience of using ibrutinib is the medication, while it does have some side effects—these are manageable, and mostly the treatment is associated with an excellent quality of life for patients.

And so we await these data with great anticipation.  I believe that the study has been submitted to the New England Journal of Medicine, and I believe that we’ll hear a presentation of these data at ASH.  So this is very much a “watch this” space for the RESONATE-2 data.

In addition, there was a lot of talk at the meeting about the potential offered by the combinations of new medications in CLL.  And I think this is very important.  So while ibrutinib has completely changed the game in terms of survival, in terms of quality of life, the problem with the medication is that patients need to continue to take it in the long, long term.  So it’s not like chemotherapy where you have six months of treatment, and then you stop.

Patients need to take the medication indefinitely.  And the rate of complete remissions have so far been low, although we would expect they’ll be higher in patients who haven’t been treated before than patients who have been treated in the relapse setting.  And so I think—patients don’t like to take medications long term.  It’s associated with cumulative financial burden for both patients and society.

And there’s always the risk that resistance can develop if there’s a small amount of CLL that remains.  So a lot of the buzz around the conference was the potential to combine ibrutinib with other medications, and in particular combine with venetoclax or ABT-199.  This drug actually on its own achieves high rates of what we call minimal residual disease; negative complete remission.  So very—where we can’t detect any CLL in the most tentative tests that we have.

And there was some very nice data presented at iwCLL suggesting that in the laboratory, the two drugs look like what we call synergy.  So that each drug enhances the action of the other drug.  And there are now studies that are underway and other studies planned using this combination.

I think this is very exciting.  I think this will be the way forward, that we’ll see combinations of ibrutinib with venetoclax.  I also think we’ll see combinations of duvelisib, which is a new medication which inhibits (PI) 3-kinase delta and (PI) 3-kinase gamma.  It’s similar to idelalisib or Zydelig.  And there is some data suggesting that this will also work in a very, very powerful way with venetoclax.  So I think this is the next thing in CLL.  The two big things are that ibrutinib will be coming to frontline therapy for all the patients, and then we’re going to be starting to see combinations of novel therapies studied which I think will be very, very exciting. 

Andrew Schorr:                  

So, as you head home from Sydney, Australia all the way on the long flight back to Houston, you have time to think about what you want to say to patients. What do you want to say back there, when you get to Houston, and what do you want to say right now to patients worldwide?

Dr. Thompson:  

I think that we’re now entering an era in CLL where we can, I think, control of the disease—indefinite control of the disease—is going to be possible for most patients.  And this is amazing.  This is a disease that up until the last few years, once patients had relapsed after chemotherapy, it was difficult to treat, and the advent of ibrutinib, idelalisib plus rituximab and now venetoclax, which is likely to be FDA approved hopefully by early next year, we now have the tools, I think, to control the disease in most patients who have been previously treated.

Now for patients who have never been treated before, this is even more exciting, because it’s always more difficult to treat patients who’ve been previously treated with a lot of treatment, because you tend to have selected out a more difficult to treat population of CLL cells.  But I think for patients who have never been treated before, I think the overwhelming majority of them are never going to have to have chemotherapy.

I think there’s still a small minority of patients—the younger and fit patients who can tolerate FCR, who have favorable genetic profile with what we call mutated IGHV gene, these patients have an expectation that over half of them will essentially have cure of the disease with chemoimmunotherapy.

So that small group of patients may still benefit from chemoimmunotherapy.  And there are some studies that are looking at combining chemoimmunotherapy with some novel therapies like ibrutinib in this patient population with the hope that we can cure an even higher percentage of patients.  While a lot of us have been hesitant to use the word “cure,” I really do think we’re moving towards that capability, at least in that subgroup of patients.

But I think moving forward for patients who are not candidates for that type of treatment, I think the tools are in place that we may see a really high number of patients with combinations of the new medications which are going to be soon studied that we can potentially see eradication of the disease.

And this is really where the field is moving.  I think over the next five years we’re going to be seeing more and more studies with combinations of these new agents that aim to treat people for a defined period of time rather than indefinitely, and really aim to eradicate the disease or get the disease down to such a low level that patients can be off treatment for a long time.  So I think this is exciting.

Some things that weren’t discussed at the IWCLL meeting but that are going on in the background are some of the new immune therapies for CLL.  I think we’ll see more of this presented perhaps at ASH, and perhaps beyond.  But some of the groups are having very exciting results in difficult to treat patients with modified T cells called CAR T cells.  This is where we educate the T cell, which is part of your immune system, to actually recognize and kill the CLL cells.

This would have been stuff of science fiction not so long ago, but it’s being done at a number of centers around the country, and it’s going to be moving into commercial development with a number of companies in that space.  This is interesting, and there are also a number of new second-generation kinase inhibitors such as ACP-196 that are showing excellent results.  So we’re really moving into an era, I think, where the majority of patients are going to have an excellent outcome from their disease, with excellent quality of life and hopefully with very few side effects from treatment. 

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 Dommunity 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 September 25, 2015