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Denise Brock

ASH 2016 Recap #2 – Update on New Chronic Lymphocytic Leukemia Drugs

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 Patient News
from the American Society of Hematology (ASH)
Annual Meeting 2016
Presented by the
Global Resource for Advancing Cancer Education

GRACE is pleased to present a series of webcasts with faculty member John Pagel, MD, PhD, DSc, from Swedish Cancer Institute. Dr. Pagel was one of many to attend the American Society of Hematology’s Annual Meeting (ASH) in early December 2016 and graciously sat down with GRACE to recap highlights from the meeting.  Our second video in this series gives us an update on new chronic lymphocytic leukemia drugs.

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  View/download transcripts here.



This is John Pagel, MD.  I am going to discuss some of the newer agents that were presented at the American Society for Hematology meeting in December 2016 in San Diego, California.   

These are newer agents in development and for therapy for patients with chronic lymphocytic leukemia or CLL.  A couple of new drugs are in advanced development that certainly are worthy of notice.  One of them is a drug that gained a lot of attention at the ASH meeting in 2015 and now has been updated in a couple of studies in 2016, and that is a drug that is called acalabrutinib. 

Acalabrutinib is a second generation inhibitor of an enzyme known as Bruton’s Tyrosine Kinase or BTK.  It turns out, of course, that BTK, is a target of the 1st generation BTK inhibitor known as ibrutinib.  Again, acalabrutinib was presented at the ASH meeting in 2015 showing excellent activity with very few adverse events and to be very well tolerated. 

Now it was updated in a couple of studies.  One study, of particular note, was a study of patients who were intolerant to ibrutinib.  Many of those patients could go on to acalabrutinib and actually have a response that was maintained and the side effects they had that may have been important for them coming off of treatment with ibrutinib were not found when they switched over to acalabrutinib.  This was a study led by Baruke Awan from Ohio State University.  I think that this is very important to know, that if side effects drive people away from a drug that is working, there is another drug that may be in pipeline on the horizon for people that works in exactly the same way but may not have the side effects. 

Acalabrutinib was also looked at and presented in a study by Peter Hellman, looking at the worst types of patients with CLL and that may have a transformation of their disease to a more aggressive form.  That is something we call a Richter’s transformation.  That was presented at the meeting and the results were quite impressive in very, very difficult patients, patients who had very advanced disease and, again, had had their disease transform to a more aggressive form.  Again, acalabrutinib is in advanced development.  I would say that we need, of course, more time to follow-up on these patients and use of acalabrutinib but, in particular, in these settings for patients with disease that is intolerant to ibrutinib or, perhaps, have become more aggressive, people can actually have significant benefit. 

I will also touch on the very important drug, known as TG-1202, which was presented extensively at the meeting.  TG-1202 is a very exciting drug in that it is another second generation drug from one that we already have approved for patients with CLL.  TG-1202 is a tyrosine kinase inhibitor and a second generation.  Second generation being that it is perhaps a new and improved version of the previously approved first generation drug known as idelalisib. 

TG-1202 suggests that it may not have the same aggressive toxicity profile that, albeit rarely, we do see with idelalisib. Particularly, perhaps we will see less diarrhea, less pneumonitis or pneumonias or lung inflammation, and, perhaps, less inflammation in the liver.  This drug has continued in development and we are very excited to see where that leads us in the next game changing type of drug. 

Of course, I should point out that these agents aren’t all by themselves.  We like to combine them in many ways and combinations are certainly the way to go in the future.  In particular, and I will mention a very important study that was led by Jeff Jones of Ohio State University and also presented at ASH, that used a combination of drugs known as obinutuzumab, ibrutinib, and venetoclax.  I have already mentioned the ibrutinib which is a BTK inhibitor.  Obinutuzumab is a newer generation anti-CD20 antibody that has excellent activity and venetoclax is new drug that targets a protein known as Bcl-2 and this actually induces cell death in the CLL cell.  So the combination, again, of the obinutuzumab, ibrutinib, and venetoclax was used in a small trial, relatively few patients, but still shows that this combination can be very well tolerated and that the side effects are very manageable and that the efficacy or the activity is quite impressive.  Everybody who was treated showed a response and, in fact, many of these patients got complete remissions at a very short follow-up.  Furthermore, many of these patients had elimination of, what we call, minimal residual disease, either in their blood or bone marrow or both.  Minimal residual disease clearance is very important for extending, what we call, progression-free survival.  This is looking down at very deep level to see if we have eliminated any of the CLL cells.  It is a method to actually make sure that in the blood and marrow, we have done an excellent job of controlling the disease. 

Other combinations are in development and, just for completeness sake, I will mention that there are trials in development using all kinds of combinations and the TG-1202 trial is certainly in development and in combination, as well, and we will see more about that as we move forward.  It is a very exciting time for these new drugs in CLL, not only as single agents but in combinations. 


We would like to thank the following companies for their support of this program:






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