Hmm...partial answers from Dr. FVR from UAMS

So I was on this panel today with Dr. Van Rhee, who did an admirable job of explaining the total therapy philosophy.

I told him I was a fervent believer in their approach, thanked him and his colleagues for saving my life, and then told him I was going to ask him tough questions.

I pointed out that the "cure curve" presentations that had formerly been featured on the UAMS site were now down, and that BB is now looking at administering Revlimid post therapy to see if there is a difference in outcome.  I wanted to know what the cure curves looked like now -- how long until a plateau is reached and what percent of patients under TT3 look like they will exit in a "cured" state.   I mean, look -- it's disturbing that the folks who have been saying they can cure this condition are (a) removing their formerly strongly-worded documents to this effect from their website, and (b) doing a test to see if medicine should really be stopped after three years of maintenance.  There could be very legitimate reasons for both of these things (for example, the papers are now 4 and 6 years old, respectively, and the ongoing maintenance could be a test to demonstrate that the existing maintenance already does as good a job as possible).  However it is disconcerting.

I'm looking back at my copies of these papers, starting with one called "The Myth of Incurability" that was published in 2007.  The original data on TT3 -- ignoring projections for the moment -- was that low-risk patients had a event free survival rate of about 80% and things looked like they were flattening out at that point -- meaning that if you made it to four years without a recurrence, you were highly likely to sustain remission.  High risk patients, unfortunately, are not so fortunate -- only about 35% of these folks were still alive, and only about 20% of them had maintained remission.  There is no claim of cure for high risk MM through Total Therapy (or any other therapy).

Based on this performance, the first projected "continuous complete remission" for both low risk and high risk combined was forecasted and showed what looked to be a 35% cure rate for both cohorts (low and high risk).  If we assume 15% are high risk that are not cured, this implies about 50% of low-risk patients being cured overall.   Bear in mind, these figures includes deaths from everything -- if somebody gets diagnosed at 68 years old and lives for 8 years and dies of heart disease, they fall off the graph.  So the cure rates are likely understated for that reason.

Moreover, performance is better for low risk patients that achieved complete remission.  Here, the forecast was for ">60% 10-year continuous complete remission" for both cohorts.  Again, if we assume that high risk patients representing 15% of diagnoses are unable to achieve 10-year continuous complete remission, that implies about 70% of low risk patients achieve 10-year continuous complete remission.  And since not all patients achieve complete remission in the first place, the implication is that a very high percentage of low risk patients that achieve complete remission are projected to be cured.   In fact, looking at another chart, it looks like of the total TT3 cohort of 303 patients (including both low and high risk) about 52% achieved complete remission, taking an average of one year (based on the median of this group) but up to 30 months to get there.  Meanwhile, the relapse rate of those who achieved complete remission fell to zero, basically, after about three years.  So if we say 18 months to get to complete remission and three years of remission to get through the time period where there is a risk of relapse, then somewhere between four and five years out people can be confident they are cured.

Fast forward now to 2009, and a follow-up paper called "Modeling for the Cure."  This paper I can't even find, unfortunately, although I'm sure I have it somewhere (probably at my office -- I may update all of this later today).  In this paper, I remember clearly the forecast was that low-risk patients that achieve complete remission have an 87.6% chance of being cured, and that by the end of four years, the plateau has been reached.  In other words, the 13.4% chance of relapse exists at the beginning of remission and is slowly reduced over four years to the point of it being basically nothing.  This seemed to tie to the earlier data.  All good, right?

I should be able to breathe easy.

Except this paper has now vanished.  It's not referenced anywhere any longer and it's as though it's ceased to exist.

I pressed Dr. van Rhee on this, and he said that the plateau now appeared to be at "7-8 years."   I'm not sure whether or not this means 7-8 years from the achievement of remission (unlikely) or 7-8 years from the commencement of therapy (more likely, and obviously better since it takes a while to get into remission).  If the plateau is reached at 7-8 years from the start of therapy -- let's say 8 years to be on the safe side -- then I've got three more years to go.

He also said that the rate of patients still in complete remission at that point was about 50%.   Now again, this includes high risk patients as well, and it includes death from other sources.  If we make the adjustment to remove the high risk patients once again, we are back to around 60% of low risk patients being cured (the number is probably higher, again, if we consider deaths from other causes as well as the fact that patients achieving complete remission is higher).  Nonetheless, worst case, 60%.  And if we assume an even "failure rate" of remission over the total eight years from therapy, I'm now just about 5/8 of the way through.  Which would imply that I've got an 85% chance of being cured, which should increase steadily over the next three years until eventually, I can rest easy.

This is all rough math based on numbers from different sources, often interpolated and extrapolated to provide approximations for numbers I don't know.  So it's far from perfect, but it's something.  It's more than a 50% chance I'm cured, and it's less than the 100% that I expected by now.

All this estimating is almost enough to make my head explode -- which, if taken literally rather than figuratively, would convolute my own statistics due to morbidity from something other than Myeloma!  :)

Which brings me to my second question for Dr. Van Rhee -- that of the monoclonal light chain under immunofixation that I have had in my blood for several months.  Is this the harbinger of remission loss? Or is it a sign of deep response to therapy that would be consistent with significantly extended survival if not cure?  The bottom line is: he doesn't know.  He seemed to be somewhat familiar with the Mayo paper that observed this, but said they hadn't observed this "secondary MGUS" at UAMS.  He did reference to a sub-population of low-risk patients that had MGUS likely before it became Myeloma, and were treated for Myeloma, and did fine (as in no return of the disease for many if not most of them) post therapy, but who retained the original MGUS.  I'm not sure I fall into this camp -- my monoclonal signature now may not be the same protein.  If it *is* the same protein, then maybe I have this "cure with MGUS" hope, per that cohort of patients.  If it is *not* the same protein, then it seems more likely that this is consistent with the Mayo interpretation of an immune system repairing itself.

I've written to BB asking this question more directly, and we will discuss it when I have my next follow-up in a few weeks (early February) if not before.

Ugh.  I'd love to be able to close the door on this chapter but the Myeloma has its food wedged in there pretty firmly.   Let's fight another day at a time, shall we?

Meanwhile, I want to have a shout-out here to my friend MAdAM (funny, that really is the acronym, but I'm not referring to this puppet

(As an aside, per my Google search that came up with this picture, it's provenance was an auction site that had "authentic Madame puppet with fainting couch" as the listing -- yikes, the mind boggles).

Anyhow, I digress.  My friend MAdAM was being treated in LA by an anti-transplant doctor of renown and was told he'd run out of options for her, she had a good run, get her affairs in order.  That was several months ago.  MAdAM went to BB and just came out of her transplant in remission, and has a plan with plenty of options going forward.  Will she live another 2 years?  Another 10?  Long enough to find a definitive cure?  Let's hope so.  One thing is for sure -- she's a lot better off now than she was a few months ago.  So for whatever long-term questions I have about the final cure fraction of TT, it remains highly effective against Myeloma.

So ONWARD, BB and team!