Some thoughts on this Revlimid situation...perhaps a false alarm?

Hello folks, and happy holidays.

There's been a bit of chatter over the last couple of weeks about Revlimid and its potential linkage to secondary cancer.  This began when some studies of Revlimid in Myeloma seemed to have higher numbers of people with secondary cancers in the Revlimid arms than the non-Revlimid arms.

I've not yet gone back to Arkansas to look at the specific data, but I have had a couple of conversations subsequent to my last post so I thought I would mention it.

First, I think there is a figure of 8% being bandied about and I think it's being done incorrectly.  The Celgene (maker of Revlimid) spokeperson said that there is an 8% chance that a Myeloma patient -- in general -- would develop a secondary cancer within a given two year period.  Now this, alone, seems extremely high to me.  But that's a separate issue.  The same spokeperson than said that the number of additional secondary cancer occurrences in the Revlimid group was within this 8% margin for error -- in other words, s/he attributed it to random chance rather than any statistically significant impact from Revlimid (or at least made the case that it could simply be random).

I'm not sure how I feel about all that -- a mixed bag, at best, but I don't think the idea that Revlimid increases secondary cancers by 8% is correct.

Probably more importantly, I had a couple of conversations about this with Dr. GD (my maintenance guy) and one of his excellent nurses (who I'll explain in a moment).  I was talking with GD in general about recent trials and I brought up the Revlimid one.  He said that he'd had many people on Revlimid for many years and had never seen a single case of secondary cancer.  That, it seems to me, is very good news.  Anecdotal rather than statistically significant, perhaps, but good news nonetheless.

I mentioned the tandem transplant statistics and GD, despite his mild reservations about some of BB's aggressive tactics, said he believes they do in fact make a difference, do cure some people, and represent a "stop gap" measure until such time as we have a more effective means of managing Myeloma.  Sounds right to me.  He mentioned that he had a couple of patients whom he urged to go to Arkansas for treatment, and they opted for less invasive treatment, and they are both very ill now...as in on their last legs.  Again, anecdotal and everybody's case is different, but it is worth noting.

GD also brought up that with one of these patients, he spoke with BB about how BB would treat.  BB mentioned VDT-PACE as induction (Velcade, Dex, Thalidomide, Cisplatin, Adriamycin, Cyclophosphomide and Etoposide...all of which I had).  GD said that the key to administering that therapy is a great deal of experience with managing side effects and palliative care, and that he (GD) would not be comfortable administering it himself.  Makes sense.  I had the same feeling when I reluctantly went to Arkansas -- I'd rather be the 1000th person going through it there than the first person doing it in California under somebody else.

I went back to GD's the following week and had a nurse I'd not met administer my Velcade.  The other nurses are pleasant enough and good at their jobs, but I feel like I know much more about Myeloma than they do.  However this nurse was extremely knowledgable.  I mentioned Arkansas and she brought up BB.  We discussed Total Therapy, etc.  I was surprised at how much she knew, when one of the other nurses came in and said "oh, you've met E...did you know her husband is Dr. RV?"  (RV, whom I've not mentioned here some time, is a prominent Myeloma specialist out in LA).  Anyhow, this led to a discussion of Revlimid.  RV has had, per his wife, "prescribes a LOT of Revlimid" and has never had any issues with secondary cancers.

More good news!

Speaking of which, all my labs look good.  I get a week off meds next week -- cannot wait -- in preparation for my trip to Arkansas the following week for MRI, PET, bone marrow, and all that good stuff.  Can't say I am looking forward to the process but I am eager to see results, hopefully, in resolution of the four remaining formerly-active lesions in my bones.  If they are all healed up, BB will hopefully breathe a little easier with me.  That's the next hurdle in the road to being cured.

Happy New Year to you all!

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...