Sunday, December 12, 2010

Asymptotes and secondary cancer...

It's been a pretty busy couple of weeks here.  At my office I have three half-written posts that never got finished!

The first of these has to do with tying the previous post (about the efficacy of tandem transplants) more concretely to what Arkansas is doing.  The study that demonstrated this was not a UAMS study.  And it was done without the benefit of any new drugs -- BB uses tandem transplants plus the most potent induction protocol there is, plus Velcade and Revlimid.  The efficacy of Total Therapy, therefore, is probably higher than the data would suggest.

But the real takeaway from that data is the notion of a plateau.  UAMS' philosophy is predicated on the idea that if somebody has not lost remission by year X, they are cured.  This was seen in a type of childhood leukemia as that disease was treated in a manner similar to Total Therapy, and that disease is now 95% curable.

People pooh-pooh the notion of a plateau in Myeloma, but I've never seen anybody explain why.  This includes my maintenance doctor who seemingly doesn't understand the statistical notion of an asymptote (this explains why I never finished the other post...I wanted to bring some graphs into this and perhaps in a post to come I shall).  At the highest level, an asymptote in this context means that instead of the chance of recurrence being equal or random over time, it grows smaller as remission is sustained and eventually disappears.  In the study below (from memory) this was noted at 11 years.  Which is about where UAMS noted it at the time of Total Therapy 1 (pre Velcade and Revlimid and Thalidomide).  UAMS is now in Total Therapy 4 and 5 for newly diagnosed low- and high-risk patients, respectively, and the plateau for low-risk appears to be at three years post-complete remission.  That means that if one makes it three years, one can go off meds and know that they are very likely cured (95% or more likelihood).

This brings me to the other issue in this post.  Revlimid.  Now key to any treatment of the disease, and an integral part of maintenance therapy for me and others treated at UAMS and elsewhere.  Last week, Celgene (makers of Revlimid) took a pounding in the stock market when data suggested that their drug causes secondary cancers, such as Acute Myelogenous Leukemia.

This, needless to say, is jarring.

The exact statistics are a little vague at this point and no dosing information is available, and whatever secondary cancers show up are probably not as bad as contending with the mortality rate from untreated Myeloma.  But I still don't like it.  Particularly because (although there is no specific data that I could find) it is suggested that the occurrence of secondary cancer increases significantly when one has a stem cell transplant.

The best longitudinal (i.e. over time) data on the use of Revlimid, of course, comes from UAMS where BB has been using it for around seven years.  That is actually three years longer than the study that was completed that indicated the secondary cancer.

So I emailed UAMS to ask them to share their own statistics with me.  They will have tracked hundreds of people under their protocol and they'll know how many, if any, have contracted secondary cancer.

I've not heard back yet...which means I may go directly to BB himself.

I'll be there next month anyway, so I will find the answer.

In the meantime...I look a little more askance at each blue-and-white pill that I take in the evenings.  It's a little disturbing...


  1. Nick, thanks for the post. I am still concerned about my little pill as well. I am on my 20th maintenance cycle. Please let us know as you find out from BB, and I hope other users of REV will comment.

    Until the newer drugs came on the scene, it was a much more difficult decision. Perhaps now the decision to discontinue may (I repeat may) be easier know that something will be in place in case I need it. The newer meds didn't work for me when I started, but DPASE + ASCT + REVMaint seem to be working so far.

    Very tough decision :-(

  2. I am with you on the Rev. Let me know what you hear from BB! I have put in the same question to Dr. J and will be in his office in a week. Also, would you mind emailing me your current maintenance regiment? We are putting our game plan together for 2011 and I want to compare notes.

    Keep dominating Nick!

  3. Nick,
    I seem to recall that the informed consents I signed before each of my 3 transplants warned of a small risk of leukemia from the chemo used in the transplant (usually melphalan). In my view the risk of AML or other blood cancers is extremely small when compared to the risks attendant with prematurely discontinuing a revlimid based maintenance regime. Haven't all of us who've gone through high dose chemo had to do this risk benefit analysis? Seems to be a no brainer to me given the mortality rate associated with untreated myeloma.

  4. Just thinking logically...which is dangerous for a numbskull like me....cause and effect between Rev and Acute Myelogenous Leukemia would seem to be hard to validate. Is the Rev causing the cancer, or is there some sort of presidposition? Are patients using other therapies, such as Velcade/Dex or, more significantly, thalidomide (which is a close cousing to Rev) having the same experience?

  5. I recall that the paperwork we signed talked about other cancers and leukemia in particular. I met TWO MM patients that were over 10 years out from their tandem transplants, both elderly, who were back for a 3rd transplant because they had both contracted leukemia. One woman, one man. Leukemia patients can only have allo, because their cells are too compromised. I thought how ingenious it was that BB collected for more than two and this was clearly one of the reasons. Always weighing the risks with the benefits. A delicate dance and widely held opinions on this or that drug or protocol.

  6. Well, what about the fact that with STC's - whether allo or auto - you have a body with either diminished or very fragile immune system which leaves one vulnerable to all kinds of things - secondary cancers included? How do you determine if the secondary situation was CAUSED by a drug instead of a compromised structure?

    It is so important to do the critical thinking - almost impossible when the doctor finishes telling you the bad news - up front... but taking the time now to have this discussion is truly invaluable. Thank you, Nick.

  7. Just to let you know Nick I am still continuing to read all your posts. I have no comment to make here today, except to agree with all Sandy has written. Keep well and strong.

  8. Interesting development, indeed. I will be continuing my maintenance treatments and taking the blue and whites nightly. I agree with the previous sentiments that right now, it is worth the potential, but not substantiated, risks. Tine and hindsight may teach us. BTW - I hadn't heard the word asymptote since college - thanks for the jolt back to yesteryear. I write shows and other things for a living - glad to know that some smart guys like you are putting higher field knowledge to work! Best!