Tuesday, January 27, 2015

Initiation and Discontinuation of Ibrutinib in Chromic Lymphocytic Leukemia (CLL)

It is not often one gets this much brain power and experience with ibrutinib around one table so I am very grateful to OncLive for arranging this discussion and wanted to share it here.

I was surprised by Dr. Byrd's hesitancy about using ibrutinib frontline.

I was not surprised by the lack of unaminity among the experts.

Here are some of the key points.

  1. The immunological modulation effects of ibrutinib are emphasized by Dr. Byrd. It is doing more than interfering with B cell signaling. Same may be true for idelalisib.
  2. The future is combination therapies, but what do we do now? Ibrutinib is approved as monotherapy. (That is why we need more trials.)
  3. Dr. Furman points out that some Imbruvica patients are continuing to improve 4 or 5 years down the line, getting to CR and even MRD negative.
  4. Dr. Kipps doesn't buy we ever get MRD negative if one uses the most sensitive tests, especially in the bone marrow.
  5. No-one really knows when to stop therapy.
There is much more between the lines here. Give a listen.

It seems there are three potential visions of how things may play out.

Below, I have grossly oversimplified the three doctors' nuanced perspectives to highlight the wide spectrum of opinions about what may come to pass with the new CLL agents.

  • Dr. Furman talks about a significant subset of patients that tolerate ibrutinib therapy well and continue to improve over long period of time, and so we argues why rock the boat and stop therapy, at least outside a clinical trial.
  • Dr. Kipps and I agree that you can't get to CURE without passing by MRD negative first, and he wants to be able to stop therapy because the cancer has been once and for all eradicated.
  • Dr. Byrd offers a slightly different possible outcome. Treat to get to MRD negative (likely with a combo), stop therapy, and then a very very long durable remission, maybe never requiring more treatment.
I am sure the difference are matters of emphasis and there is much agreement. And much uncertainty.

As Neils Bohr, the Nobel prize winning quantum physicist said: Prediction is very difficultespecially about the future.

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Blogger Unknown said...

For now, just controlling CLL w/out a CR is great! People take pills for cholesterol, heart, hypertension & many other conditions/diseases & can't ever hope to get off of their medications either. Taking daily pills is no big deal!

January 28, 2015 at 6:48 PM  
Blogger Dr Nickel said...

Brian -- First of all, I love your blog and wish I could get updates delivered to me automatically via email, can I? I did FCR 4 yrs back and this year at the annual Bay Area LLS meeting on the year's research it finally got thru to me what the new oral targeted ones are really about ... CR or MRD or whatever you want to call it is off the table and it's about expensive pills forever. I don't like the monetary aspects of that at all, but it's the personal and spiritual aspects that really get to me. The idea that we're no longer undergoing a difficult treatment, then recovering and finally back feeling more appreciative of life than ever -- that we're now integrating their pharmaceuticals into our lives day after day, it just takes all the wind out of my sails, makes me feel on a leash and tied into a corrupt industry. I know this is kind of a rant. Normally I'm a calm and rational guy, but the scenario I saw for myself at our LLS thing just a few days ago really shook me up. Thanks for listening. - Tom

January 28, 2015 at 9:38 PM  
Anonymous Anonymous said...

Can you explain what is meant by immunological modulation effects? Is this a good thing or bad thing? When I google immune modulation, one definition states it is the "adjustment of the immune response to a desired level." This seems like a good thing to me.

Thanks for all you do, Brian!

January 29, 2015 at 7:50 AM  
Anonymous Anonymous said...

I know folks who have been in remission for years from various cancers, and they all have one thing in common. The feeling that they always have to look over their shoulders, fearing the return of cancer. Whether I am on pills indefinitely or stop them due to achieving MRD (a cure?) I will never live my life in the complete innocence I had before cancer. I will always fear that return, watch for symptoms, and pray my labs are clean.

January 30, 2015 at 10:03 AM  
Blogger Jeffrey Zuckerman said...

My sentiments as well. That is the psychological component that haunts me.

January 31, 2015 at 4:05 AM  
Anonymous Marti Schmidt said...

This is the best blog on the subject of CLL I have read. Thanks Brian for all that you do, I read your info with great anticipation and hope.
I am a new CLL patient in Wait and Watch phase (UGH) but looking forward I seeing what the future may hold for a complete remission for me.

February 17, 2015 at 7:34 AM  
Blogger cam thomson said...

Thanks for taking the time to discuss this, I feel strongly about it and love learning more on this topic. If possible, as you gain expertise, would you mind updating your blog with more information? It is extremely helpful for me.
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April 6, 2015 at 4:00 AM  

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