At ASH 2016 in San Diego, CA, I had the honor of once again interviewing Dr. Wiestner from the NIH (National Institute of Health) about the prototype BTK inhibitor, ibrutinib and how and why it works so well in CLL.
We have known for a while that for its survival and well-being, our cancer is dependent on BCR (B cell receptor) signaling. Blocking BTK (Bruton’s Tyrosine Kinase), blocks that BCR signaling and that blocking usually leads to our cancer’s retreat.
This is a well-understood critical tenet of why ibrutinib works as well as it does, but it is hardly the whole story as we are learning over time.
At the NIH, Dr. Wiestner and his team not only did some of the earliest clinical research on ibrutinib, but also has been doing the bench science on exactly how it works and its impact changes over time.
Thanks a lot for this, Brian. Very encouraging to hear that ibrutinib often had a significant impact in the first four weeks and that this effect becomes more pronounced over time.
Agree with Brian, Ibrutinib is an amazing break through for us CLLers. We tend to focus on the side effects or symptoms appearing down the line with treatment but I have found Ibrutinib completely changed my life. Within the first two hours of taking the first pill I could feel a difference, really unbelievable.
Thank you very much Brian. This is a great interview for a patient to see. We are all waiting to see if acalabrutinib can be as efficacious with the possible benefit of fewer AEs secondary to fewer kinases being blocked unnecessarily. Dr. Wiestner's comment on BTK mutation being a primary reason Ibrutinib might ultimately fail suggests the need to work around that eventuality.
Thank you very much Brian, very important and useful information ! However I can't help wondering if the BTK mechanism is so critical for CLL how do we explain that you get deeper ( mrd- ) and faster remissions with Venetoclax that inhibits a different pathway ? Could it be that Venetoclax actually kills the CLL stem cells but ibrutinib doesn't ?
Yes, Venetoclax tips the cancer's cells balance towards apoptosis or programmed cell death, so it kills faster and deeper. That is probably a very good thing, but honestly we don't know for sure.
I started Imbruvica two days ago and my neck nodes(3x2cm) are noticeably lessened in size,, I have also had two infusions of Rituxin. I am being seen at MD Anderson and after my 1/18/17 diagnosed was placed at stage IV. MDA was my second opinion.
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Zanubrutinib vs. Ibrutinib Patient Power Video by Dr. Jennifer Brown MD PHD
