What happens when we fail ibrutinib


Last week in the Conference Coverage section, we’ve posted another interview with Dr. Susan O’Brien out of UCI where we discussed an important paper from ASCO 2016 that cleared up some confusion about what happens when patients fail on ibrutinib. You can view that interview here. cllsociety.org/2016/09/asco...

This is a really important topic that has been badly misunderstood and highly recommend you take a look at the interview.

In the meantime….

Stay strong.

We are all in this together.

Brian Koffman, MD


5 Replies

  • Thank you Dr. Koffman and thank you for doing what you do! Since Ibrutinib is most effective frontline, it seems reasonable that this would be the best choice for first treatment (unmated, mixed karyotype, 11q del). Better to use it upfront, then after failing other options. My reservation, is that relapse on Ibrutinib is challenging but maybe Venetocax can fill that role. I guess they can't yet discern whose BTK may mutate and thus make I less effective. That would be great to know of course but I'm asking for too much (lol).I wonder if anyone has correlated disease burden with response to Ibrutinib. In other words, does it make sense to use when tumor burden is lower rather than higher?

  • 11q deletion is less likely to relapse after ibrutinib. Yes relapses can be problematic but the problem is overstated and the options are improving. Take a look at the Jeff Jones and Susan O'Brien interviews that we recently posted

  • There are clinical trials right now looking at this specific question.

  • This is extremely informative material - have to show it to a local doctor who strongly believes Ibru should be witheld until all other options fail :)

    My question is this, and this is my predicament....

    The understanding is the there are 3 meds for CLL which are generally accepted in the US to be used in the following order should the previous one stop working... Ibru, Venetoclax, Idelalisib...

    What to do if one has no access to Ibru but can potentially gain entrance into a Venetoclax trial? Can Ibru and Venetoclax be taken in the reverse order should the initial therapy start with Venetoclax and it eventually stops working?



  • Hi hanskloss/Andrew,

    I think your local doctor should view this video:


    Here is the abstract. At ASCO 2016, Dr. Susan O’Brien of the U. of California Irvine (UCI) was the lead author on an important paper that cleared up some confusion about what happens when patients come off ibrutinib.

    There has been data suggested that when patients failed ibrutinib, the outlook was dismal.

    Dr. O’Brien explains that finding and offers a broader and more upbeat perspective based on her study presented at ASCO 2015.

    Take Away Points:

    Both frontline and relapsed patients have high responses rates on ibrutinib and relapses are rare. This is not news.

    More of those who start ibrutinib after having relapsed from multiple other prior therapies fail on ibrutinib. Again this is not news.

    Patients from the early trials that relapsed after multiple lines of therapy on ibrutinib obviously had very few options and also had aggressive disease explaining their poor outcomes.

    However the few patients who fail ibrutinib after no or only one line of prior therapy do very well post-ibrutinib. Median survival has not yet been reached. Some may not need therapy for a long time.

    These patients have many options now that both approved and within clinical trials that were not available until very recently.

    When we read trial results, it is critical that we understand who the patients are that are being studied and not to generalize the data to all patients who might take the trial drug in other circumstances. This is another argument for the importance of having a CLL expert on your team who closely follows the research.


    I am one of very few patients that have had all three of the USA approved targeted therapies (Idelalisib/Zydelig, Ibrutinib/Imbruvica & Venetoclax/Venclexta). The first 2 were approved in 2014 and Venetoclax in 2016, so there is little to no data yet about the pros / cons of taking any of those three in a specific order- mostly due to the timing.

    There is a current clinical trial at Ohio State Univ. that combines 3 drugs in different order (Ibrutinib, Obinutuzimab/Gazyva, Venetoclax), but most of the patients are just completing 6-12 months on Venetoclax in that trial.

    I am currently on Venetoclax with fantastic results, and several of the OSU trial patients have posted great results so far. Also you should look at the postings by debinoz - who flies from Australia to London to get her Venetoclax refills on a UK trial.

    So I doubt that anyone can answer your question about sequence, but if I did not have access to Ibrutinib but could get Venetoclax, the decision would be easy for me. Go for it!


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