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ONYX Pharmaceuticals, AŞ Message Board

  • bearofbleecker bearofbleecker Apr 5, 2013 6:41 PM Flag

    Net from Highlights of International MM Workshop webcast.

    This was a webcast summary of the MM Workshop sponsored by the the MM Foundation. The participants were Dr. Ken Anderson, from Dana-Farber in Boston and Dr. Sundar Jagannath from Mount Sinai in NYC.
    To understand the importance of this vis-à-vis ONXX, you should first understand the current protocol for MM:
    If your blood tests and subsequent bone marrow biopsies show evidence of MM, but you are otherwise asymptomatic, you are categorized as having "smoldering multiple myeloma". They do not treat you at this point. There is a 75% chance that you will progress to fullblown MM - diagnosed by an "M Spike" in your blood tests - at which point they begin to treat you. This is usually a combination of Revlimid , Velcade and dexamethasone. For younger people, this is "induction therapy" designed to get the malignant cells down to a point where they can harvest and freeze your T-cells preparatory to a cell transplant. (Heavy duty chemo, after which they transplant your own T-cells, which usually gets you back to square one.) For older patients, who can't withstand the rigors of chemo, when this therapy stops working or the Velcade is causing serious peripheral neuropathy, they switch you to something new. This is where Kyrpolis comes into play. It's a limited role and rather late in the game, but it's the only thing that might work at this point. (All of the foregoing is vastly oversimplified.)
    Here's the news: The key presentation at the conference will be the trial using Kyrpolis, Revlimid, and low-dose dexamethasone in newly diagnosed older "smoldering myeloma". Anderson referred to this in his summary as "an apparently positive trial". It was obviously a good deal more than that, since the theme of his presentation was that the whole current treatment protocol is wrong. The evidence now is that you should start "combination therapy" at the "smoldering myeloma" stage in all newly diagnosed patients, hoping
    to avert the need for chemotherapy. (continued)

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    • Bear, Sorry to ask this question again but are the results of the two studies by Landgren and Jakubowiak available?

    • (Part II) Further, when stem cell transplants are done, the new thinking is that this same "combination therapy" should be continued as maintenance. The three key elements of this combination (although Anderson thinks that ultimately there will be more than three) will be Revlimid or Pomalyst, Velcade or Kyrpolis, and dexamethasone. The problem with using Velcade long term, of course (my observation, not his) is that it causes progressive peripheral neuropathy. Painful and eventually, as it becomes less peripheral, serious. The prospect here is that rather than being given Kyrpolis as a last resort, after the patient has failed on Velcade, it will be one of a combination of drugs given in the very first stages of diagnosis and, potentially, continued as a maintenance therapy. The view of both Dr.s Anderson and Jagannath is that MM, rather than being "cured" by aggressive treatments, will be suppressed by longterm combination treatments. My analogy would be to Gilead, which has not cured HIV, but which, by combining various suppressive drugs, has made it a chronic condition rather than a death sentence.
      The implications of all this are very good for ONXX. (This conference is held every two years and is central to the way that MM is treated worldwide.) They are probably even better for CELG.

      • 1 Reply to bearofbleecker
      • I love the fact that some numbskull is giving me a "thumbs down" for reporting this stuff. Here's an additional fact for his/her disapproval: Over 69% of those diagnosed with MM are over 65. So the outcome of the featured trial, which suggests that these people should be treated with combination therapy right away is important. Basically, if you wait to treat them, they will progress to the stage where chemo is an unattractive option and stem cell transplant is impracticable. The Logic advanced by Anderson/Jagannath is, therefore, that the majority of MM patients should be treated with a proteasome inhibitor (probably Kyrpolis) in combination with rev/dex right away.