Is the combination of Imbruvica & Rituxan more effective in treatment of CLL?

I have been on Imbruvica for the past 74 days. I feel good with no side effects. My haematologist oncologist in San Francisco believes adding Rituxan would be more effective in keeping the disease away for a longer time. So far, except for one study in MDAnderson I haven't been able to find any other document to support his recommendation. Does anyone knows more about this?

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  • There was a letter recently in Blood from Dr. J. Byrd et al, suggests that ibrutinib and rituxan, are antagonistic... meaning they effect one another...

    'Surprisingly, our preclinical investigation of the combination of ibrutinib and rituximab results in antagonistic effects. We demonstrate that the abrogation of both rituximab’s and trastuzumab’s antitumor efficacy is a result of ibrutinib’s inhibition of FcR-stimulated NK cell function, specifically ADCC. Selective BTK inhibitors or alternative ibrutinib dosing schedules, sequential vs concurrent, may preserve the anti-lymphoma efficacy of both agents.'

    The thought is to use Imbruvica (ibrutinib) and rituxan, sequentially rather than concurrently...

    You might want to print this out for a discussion with your doctors...

    Ibrutinib antagonizes rituximab-dependent NK cell–mediated cytotoxicity

    ncbi.nlm.nih.gov/pmc/articl...

  • > The thought is to use Imbruvica (ibrutinib) and rituxan, sequentially rather than concurrently...

    I would agree with that. Let Ibrutinib do the heavy lifting clearing out your CLL for a while and then decided if you want to add a CD-20 to the mix.. I've been taking it for 3 years and have all my blood parameters back in normal ranges except a couple of immunoglobulins which are just a little below range. If my oncologist suggested that to me I would refuse to unless she offered some extremely good reasons.

    Only thing I can think of off hand is if you are in *really* bad shape and need to get the lymphocytes down Right Now. Adding a rituxan or similar does, I think, generally speed up the process. In my case since I had no serious complications I didn't care if it took one month or six to get my counts down to something reasonable.

    Plus Rituxan is rather old and a little rough on you. It's a 1st gen anti-CD20, there is some newer stuff out there or in trials -- ofatumumab (Azzera) and ublituximab (TG-1101).

    Hmmm .... just looked up my records. It took 7 months on Ibrutinib to get my WBC from 60k/uL down to normal range and 14 months to get absolute lymphocytes to normal.

  • The combo of Rituxan & Idelalisib has proven to work well together, but as Chris (CLLCanada) posted Dr. Byrd's team found the Rituxan & Ibrutinib to work against each other. As you observed Rituxan is old/first generation. There are trials just starting now - using the 3rd generation - Gazyva (Obinutuzumab) and ABT-199 for patients that progress on Ibrutinib or Idelalisib, and there is a faint hope that combination might generate very durable Complete Remissions like those from FCR. Maybe not a cure but one step closer.

  • Yeah. But one thing I forgot to mention is that, unless you are part of the 5% or so who develop a resistance to Ibrutinib, it by itself will "keep the disease away" for as long as you take it. Or at least 3 years, which is how long I've been taking it. Sounds like an old school "hit it hard" oncologist who is not quite up to speed with the "pill a day" new world.

    Complete Remissions are nice, and we'll probably get there with some combo, but since I now have essentially zero side effects popping my PillADay and going on with my life works just fine.

  • Thank you guys for replying to my question.

    I know at this time, at Stanford University they are recruiting patients for a randomized phase III trial studies rituximab with bendamustine hydrochloride or ibrutinib to see how well they work compared to ibrutinib alone in treating older patients with previously untreated chronic lymphocytic leukemia:

    med.stanford.edu/modelsite/...

    Also, at MD Anderson they are conducting the same studies:

    utm-ext01a.mdacc.tmc.edu/De...

    Please let me know your thoughts on that. Last but not least, I believe, Dr. Jan Burger at the University of Texas MD Anderson conducted similar clinical trials in 2013 and he reported 95 percent response rate among CLL patients. If I find the article I will post it. Thanks again.

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