Provenge and The Mayo Clinic

I have had a number of requests for further info. I went to The Mayo Clinic for the Choline 11 Pet Scan, and when I saw Dr. Eugene Kwon, I asked him about Provenge. His answer was I was not a candidate at this time, and Provenge could effect the immune system in a negative way, and that he had a number of cases where Provenge made the cancer worse. I think Dr. Kwon is one of the top immunology experts in the U.S. Personally, I think Huber might be on to something because it is a possible explanation of what Dr. Kwon saw. I am going to wait for the newer immune treatments in the pipeline, unless someone can convince me, Provenge will not adversely effect the immune system in a way that will make the newer treatments less effective.

Gus

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  • I have to disagree. I will upload Dr Kwon's talk from the 2016 PCRI Conference, where he warns about "small cell" prostate cancer, which is the neuro-endocrine version that seems to now be lifting its head with the extended survival from other treatments. He cautions against the hope for a "silver bullet" since cancer is heterogenous, although he acknowledges that everyone has long known that cancer is heterogeneous - they just sometimes act as though it is all the same. If you can find anything more explicit on his attitude towards Provenge, or can say more concretely what it is he is worried about, I'd love to see it. I think it is the material covered here - Neuro endocrine prostate cancer.

  • I will send an email to Dr Kwon asking for a comment, but he is not too good with emails.

  • I hope no one would put more confidence in a recollection of a comment than in a phase 3 clinical trial result; ie, base your choice of your treatment on this post.

  • Here is Dr Kwon, again at 2016 PCRI, taking about immune therapies, including Provenge. His point is that Provenge, as a vaccine, prepares the body for "checkpoint" treatments like PD1 and CTLA4. The surprise was that where there are lots of dead cancer cells, PD1 and CTLA4 are already ready to respond, and Provenge is less significant. You dont need Provenge to present a snippet of the cancer cell to the immune system. The ways to gets lot of dead cancer cells are the usual ways: freezing, heating, chemo, radiation.

  • This is the Jim Allison that he is referring to.

    cancerresearch.org/our-stra...

  • So, to put it simply, Dr. Kwon is saying that if you have had chemo, Provenge is superfluous????

  • Well sorta yes.

    He does say:

    1. Provenge may have some ability that we dont fully understand, and

    2. Combining Provenge with a checkpoint blockade is a natural

    [that is, in association with PD1 and/or CTLA4]

    2a. This idea is in trials now (ie not available except in a trial)

    3. He thought that "antigenic priming" [a vaccine, like provenge] was needed for PD1 and CTLA4

    4. They found they got a good effect [for PD1 and CTLA4] without a vaccine

    5. The immune systems reaction to dead cancer cells already amounts to "antigenic priming"

    6. The difference between a responder to PD1 and a non-responder is that the non-responder [does not have a lot of dead cancer cells lying around]

    7. So number 2 should be combining dead cancer cells with PD1, not necessarily combining provenge with PD1

    =====

    Here is the crazy part:

    He focuses on PD1/CLTA4 but you cannot get either at this time outside of a trial, so how #2 reads exactly does not make all that much difference (right now - and by the way do try to find and get into a trial of PD1, even if it is with Provenge) to get that "rip-roaring" response

    and

    As to #1, clinical trials do show a survival benefit to provenge, that he says he does not understand the mechanism of.

    ---

    That's my reading of it.

  • His comment is not really all about Provenge. His comment is really about "checkpoint blockade". It is tangentially about Provenge.

    "Checkpoint blockade" refers to the fact that T cells have a protein on the surface called PD1 that, it engaged, turns off the T cell. This can be useful during pregnancy. Call it an anti-T-cell feature. Checkpoint blockade is an anti-anti-T-cell strategy.

    Kwon is saying that the cancer cells are already creating T-cells against the cancer, but the cancer is doing the PD1 thing to them. All you "really' need is the anti PD1 ligand (or the CTLA4 version).

    Of course its not quite that simple. Chuck Drake (in another thread) talks about this.

  • I'm new here so it takes me a while to digest stuff. Are there any check point blockade treatments today? Any in the pipeline?

  • Lakefisher - oh yes. lots. None approved for prostate cancer. Keytruda is one for melanoma. It's the one Jimmy Carter got. The Keytruda trial for prostate cancer just barely failed, probably a bungle, but the trials are expensive, so that one is probably off the table for a while. ipilimumab (yervoy) is in trials. and Opdivo is in trials, and I am confident that there are many others in various stages. Finding one is a good idea and joining one that you yourself find worthwhile (you think the idea is sound, or the guy looks persuasive on YouTube, or you have some reason to believe in)

    It could be that the drug has proven to be effective for other cancers.

    I myself am hoping to find a checkpoint trial to join, since I am in the middle of Provenge, and adding a checkpoint treatment is a natural, as Eugen Kwon said.

    ipilimumab should have a trial opening early next year at Weill Cornell Medical Center in Manhattan - I hear. I assume the selection criteria will be generally mCRPC, and not include a "failed abiraterone", ie "progressed on abiraterone", ie taking abiraterone.

  • Thanks. I'm close to Duke and UNC. Maybe they have something going on.

  • As far as "checkpoint blockade", I think a clearer way to say it is that most cells have a "kill me" button on them. T-cells have one called PD-1 (short for Programmed Death 1. clever eh?). Apparently the cancer cells push this button, using their finger protein, the PD1 ligand (PDL1). The "checkpoint blockade" strategy is to block that "kill me" button. The complication (of course) is that there may be more that one of these "kill me" types of buttons on the T-cell, and I think that is why, for example, people talk about CTLA4. It must be another one of them. I have to check wikipedia on this. I suspect it's all there.

  • Yes, that is what he is saying: that if you have had chemo Provege is kinda superfluous (to use your word), but he says it in the context of getting checkppoint inhibitors, since that is what he has worked on.

    My understanding of what he is saying is that if you take checkpoint inhibitors (and he feels they are a good bet), that whether you have had Provenge or not is not the key question. The key question is whether or not your immune cells have had pieces of the cancer presented to them by antigen-presenting cells, of which Provenge is just one mechanism to do it, Provenge being artificially created antigen presenting cells.

    The clinical trial presents evidence that Provenge, by itself, is not 'superfluous".

  • Gus,

    I too am a patient of Dr. Kwon. I've had 5 C11 PETs. Simply put, he knows of what he speaks. I am also being treated locally by Stanford. Trust him about Provenge. What are you taking now? Zytiga? Wish you the best; you're in excellent hands! Let's keep kicking the can down the road in hopes of more options!

  • When you say "Trust him (Kwon) about Provenge", what is it that you think Kwon says about Provenge? What claim do you think Kwon is making that you think Gus should believe?

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