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!

Myeloma panel with Dr. van Rhee of UAMS next Monday

Next Monday I am participating as a patient panelist on another Cure Talk call, hosted by the wonderful Priya Menon and the Cure Talk organization, which will feature Dr. van Rhee who is BB's head of research.

As of now, I plan on asking him about the current cure curves for TT3 and TT4 -- TT3 data is now 10 years out so the low risk patients should have achieved a true plateau is there is one.  The last data that was routinely spoken about was in a 2009 publication called "modeling for the cure" but that data has been pulled down.  Is this because the data did not hold up to longer-term study?  Or for a less distressing reason?  This reporter wants to know!

I'll also be asking very specifically about the monoclonal light chain that is believed by some to be a sign of disease eradication but could also be disease return.

It should be an interesting conversation -- all of the ones in which I've participated have been very enlightening.

The call is December 16th at 3PM pacific time, 6PM EST.   Registration and dial-in information is below for those interested.

Have a great weekend!

Registration link:  http://curepanel.carefeed.net/event/rsvp/12/

                   Dial-in:  718-664-6574

No longer suffering from chemo brain

I went to a neurological oncologist to get a "new baseline" for my cognitive abilities.  I wanted to make sure that I had survived chemo brain.  Frankly, I went through a period in my job where I wasn't thinking as adroitly as I was accustomed to and lacked a lot of energy.  It impacted my performance and career prospects, and frankly was something that I had heard existed but didn't really understand.  I'll say this -- it's difficult to self-diagnose when you have it.

Essentially, high dose chemo of any kind bathes your brain in chemicals and there's an impact on executive function -- attention, memory, focus, energy, decision-making, etc.  These are the types of things that executives (duh) rely upon in their jobs.  It usually takes around four years, it turns out, for these effects to subside.  The amount of chemo I received would indicate that I should have this worse than most, but my age and general mental acuity before all of it would indicate that I would fare better than most.

Anyhow, I'm relieved to report that I scored off the charts on most of the stuff including the areas that were once impacted.  My IQ is 98-99th percentile (140+) and executive function is intact, as are memory and attention.  I'm under a tremendous amount of emotional stress right now due to everything from the overall cancer situation, the M protein signature that has appeared, the car, my job (stressful on the best day), and other things and that's depleting energy so I've got to find a way to deal with that, but the core intellect and processing power is back.  So onward!

Enough already! Or, be thankful and hugs your kids.

So here I am, busy not dying from cancer, when I almost died from an auto accident.

Near as I can tell (because I couldn't see anything) a truck with a flatbed / auto carrier ran into my left rear quarter panel hard enough to severely bend my rear axel, wreck the wheel and tire, activate the side air bag (which exploded with a force and sound that immediately deafened me) and spun my car counter-clockwise.  So I went from moving along no problem to being deaf and having the car spinning wildly out of control before I had any idea what was going on.  Then, as I was spinning, part of the same truck (near as I can tell) rammed full force into the passenger side of my car with enough force to knock me across three lanes of freeway traffic to come to rest facing the wrong way in the slow lane on the freeway.  All of this at 45 MPH, mind you.

Somehow, I walked away from this unscathed, other than deafness (hopefully temporary) in my left ear from the airbag going off and first degree burns on the back of my left arm and on my left side from the same airbag.

I might add, had the car flipped (which it certainly could have) I would have tumbled off this stretch of freeway over an 80 foot drop-off.

Then the driver of the truck -- which was the only other vehicle involved since no other cars were struck, miraculously -- drove away.  Nice guy.

Look, I realize my great great grandmother back in the old country spit in the eye of the village witch and invited a curse upon the family but ENOUGH ALREADY WITH THE NEAR DEATH EXPERIENCES!!!   I'm not gonna beat supposedly incurable cancer just to die in a car accident, for Pete's sake!

Happy Thanksgiving to you all.  Not gonna lie, I'm half in the bag here already from a few mimosa and I envision spending the rest of the day in a bit of a haze so...this reporter is signing off.  : )

Past and future Myeloma panels

Hello folks.

I had the opportunity to participate in another Myeloma Panel hosted by Cure Talk and the wonderful Priya Menon.  Last week's guest was Dr. Asher Chanan-Khan of Mayo in Jacksonville.

Dr. Chanan-Khan was speaking about monoclonal antibodies (elotuzimab, daratumumab, etc.) which are emerging therapies that didn't exist even a few years ago.  They're exciting because most of the developments in Myeloma over the past five years -- chiefly Carfilzomib and Pomalyst -- have been continuations of existing families of drugs.  Carfilzomib is a proteasome inhibitor, like Velcade, and is essentially a more effective version of the same drug.  Pomalyst is next generation Revlimid, which itself was next generation Thalidomide -- all immunomodulatory drugs.  And like Carfilzomib vis-a-vis Velcade, it's more effective and is easier to tolerate.  Because Velcade and Relimid are themselves so effective against Myeloma, and because Carfilzomib and Pomalyst / Pomalidomide are effective in patients that have MM with resistance to Velcade and Revlimid, Car and Pom are usually used as "salvage" therapy to extend the lives of people who have otherwise run out of options.  This is all good and fine, and 18 months may be a lot of time to somebody who is otherwise looking at packing bags (not to be overly morbid).

But 18 months isn't long enough for somebody that wants to live many years.  And so new drugs that are whole new ways of attacking MM have special interest.  There are others (believe it or not, one is called a hedgehog inhibitor) but the ones that are now "in market" so to speak (meaning in Phase III trials) are monoclonal antibodies.

I knew very little of these prior to the call, so I was excited to learn a bit about them.

Essentially, myeloma cells express certain proteins -- these have names like CD138, CD38, CD27, CD45, etc (the CD stands for, I think, "cluster designation" since the proteins are in clusters).  Monoclonal antibodies attach themselves to these proteins and allow the body's immune system to attack them, killing or weakening the cells.  Consequently, these are effective both on their own and in conjunction with other therapy (e.g., Velcade, Revlimid, etc.) that kill cells.  As a result, adding an antibody to treatment with Velcade can reduce drug-resistance to Velcade.

Because not all MM cells express these proteins, and because the key is still getting a weakened immune system that wasn't particularly good at getting rid of MM in the first place to respond and kill the targeted cells, this is not a perfect therapy and it's not a cure.  But it does represent an advancement and, combined with other therapies, could make a significant impact.

Looking at my MRD test, UAMS tested for the presence of seven proteins in my marrow (CD138, CD38, CD45, CD56, CD81, CD27, CD20 and CD19, for those playing the home game).  Of the 3,562,010 cells analyzed, none exhibited any of these proteins.  That sounds good!

On December 16th, there will be another panel conversation and the guest physician will be Dr. FVR, who works for BB.  I will have some specific questions for him about the current "cure curves" for Total Therapy 3 and 4, now that there has been 10 years of follow up for the first group and five for the second.  I will also be asking about residual monoclonal protein, per my last post.

If any of you have other questions, feel free to post them in response to this, or email me and I'll see if we can't get some of them answered.

Meanwhile, for those that celebrate the holiday, let me extend a hearty Happy Thanksgiving to you and your families!

More research on the new protein

As I suspected, Mayo was not willing to let me have a phone conversation about this particular topic.  So rather than contemplate flying to Rochester, MN in winter for what will amount to a 10 minute conversation, I'm going to see if BB will be kind enough to arrange a scheduled call with Dr. K or Dr. VR when I next visit UAMS, if not sooner.   My local guy could also call one of them -- but I'm sorry to say I'm not sure they would take his call, as busy as they are.

In the meantime, I've done more digging.

The prevailing wisdom as of 2006 -- as agreed upon by a host of doctors, including BB, VR and several others with whom I have consulted (GT, KA, PR) or mentioned here -- was that any return of protein under immunofixation constitutes disease relapse.  That would be bad.

In 2008, however, this study, published in the British Journal of Haematology, noted that people with a "high degree of response" to therapy exhibit "atypical serum immunofixation patterns."  They go on to say that this is "not associated with new clonal plasma cells or other lymphoproliferative processes, and molecular remissions were documented."  Molecular remission is no longer the state of the art but it does mean that people in complete remission can exhibit monoclonal proteins under IFE.  In fact, in their study of 72 patients, these patterns were seen in 71% of those who achieved complete remission under their protocol, versus in 23% of people that did not, and they were seen in 100% of those who exhibited some response to therapy.  Now these include those with oligoclonal protein, which I had as well -- not everybody had monoclonal secondary MGUS.  This study is one of the ones referenced by the Mayo paper yeterday.  The other is quite old, and didn't have much to add.

In this British study, they had a couple of observations.  The first is that while they used to see this in post-transplant patients, they now see it in people that DIDN'T have a transplant as well.  They take that as a sign that novel drugs alone are able to achieve the same depth of response as transplants, and they anticipate seeing more of these proteins as therapies are more effective.

The second piece of information is rather interesting.  Their hypothesis on what causes it is roughly as follows:

* The spectrum of proteins in our immune system is like a cup of water that must always remain full.  The cup itself may get larger or smaller (consider this the total protein number) but regardless of the size of the cup, it must be full of water (the individual proteins).

* With myeloma, the monoclonal protein crowds out the normal protein and results in a non-functioning immune system.  As M protein goes up, it displaces the regular part of the immune system.

* When the myeloma is beaten down, the immune system gradually returns in order to fill the cup back up.

* If the myeloma is treated particularly well, there is so much myeloma gone before the immune system can fill the glass back up properly that the water that's in the cup looks around and says "oh crap, we better make more of ourselves" but that results in some non-cancerous duplication since there isn't enough "original" water to keep the cup full.

The more medically correct (and jargon-filled) version of this is as follows:

Recent reports demonstrate that in normal bone marrow, there is a plasma cell compartment that has a capped, or finite, population of cells. In order for new, normal, plasma cells to occupy this bone marrow niche after antigenic stimulation, older plasma cells must be replaced (Odendahl et al., 2005;Radbruch et al., 2006). It may be possible that BiRD therapy (or high-dose chemotherapy) clears the bone marrow of malignant plasma cells in such a rapid and complete manner that an environment is created that allows benign plasma cells to expand within the predefined niche without competition. Certainly, the wide spectrum and variability of the ASIP protein isotypes, the recent confirmation that normal plasma cells express the inhibitory FcγRIIb receptor which suppresses normal polyclonal Ig expression, and the finding that administration of tetanus toxoid vaccine after stem cell transplantation induces oligoclonal banding patterns, all support the theory of rapid oligoclonal plasma cell expansion after the clearance MM cells as a potential cause for ASIP generation (Gerritsen et al., 1994; Xiang et al., 2007).

Once again, though, what's important is to be sure that the new protein is NOT the same as the original protein.  So I'm back where I started, kinda: if this is the old protein, I'm in deep doo-doo.  If it's a new protein, it's probably consistent with profound remission or cure.

I *must* get that blood immunophenotyped.

New energy to get to the bottom of this new M protein

Howdy folks.

So I got my monthly tests back last week and saw that "faint monoclonal lambda light chain" present under IFE.  Still nothing under SPEP.  But this isn't noise -- it's not going away on its own.

I need to get to the bottom of this.  It's not like me to sit back and just let this happen without thoroughly understanding it and taking appropriate action.  I think I was occupied with the first order question -- is this bad? -- and then when information was (as with everything with Myeloma) equivocal, I reverted to trusting in BB to see what happens in January.  And I do trust BB.

But this isn't proactive enough for me.

I first took a look more thoroughly at the work that is out there on this topic.  The most direct reference is from work done by Mayo, Minnesota, published in 2011.   The full article can be found here.

First, secondary MGUS refers to a new monoclonal protein, distinct from the original protein.  We will need to determine whether or not the protein I exhibit now under IFE is different from the one I originally presented with.  This can be done -- hopefully -- through a process called immunophenotyping.  A bunch of antibody tests are done on the blood to help triangulate it.  I have asked BB to have this done when I next visit UAMS in January, although I would like it done sooner.  Like, now, basically.  I asked BJ (BB's right arm) to look into this for me last week, but as UAMS is planning for the ASH conference in two weeks it's probably fallen between the cracks.  I will gently prod.

Anyhow, back to the Mayo article.

The highlights:

* They looked at almost 2,000 patients

* 6.6% of these patients had a secondary MGUS

* A good portion of these were in complete remission for the primary Myeloma at the time they developed the secondary MGUS

* Among the population that received a stem-cell transplant (about 25% of these patients -- 458 of them) 104, or 22.7%, were identified as having secondary MGUS.  Among patients who were followed at least 8 times over two years (248 of this 458) the incidence rose to 36.2%.   So of people that transplanted and were monitored regularly, over a third of them exhibited a secondary MGUS.

* It has been hypothesized that secondary MGUS is the result of "recapitulation of early B-cell ontogeny following stem-cell transplant."  I am informed by an online dictionary that ontogeny is the development of an organism.  So this is the immune system reasserting itself.  Sounds like good news -- but it's just a hypothesis.

* "Overall survival was significantly superior in MM patients who developed secondary MGUS compared with the rest of the cohort -- 73 months versus 38 months."   This is plainly good news.

* "The occurrence of a secondary MGUS 6 months after transplant was associated with better OS, median 102 months versus 68 months."  This, too, is good news.  Median survival of 9 years.

* In conclusion, "secondary MGUS is a favorable prognostic factor for OS, independent of year of diagnosis, age, stage and renal function."  Again, good news.

HOWEVER...nothing is this simple.

If I look at some of the key citations referenced in this article, there are qualifications.

* The statement right after that conclusion is "this is consistent with findings from other studies."  However, following that citation leads me to Dr. GT, who told me that he needed to know more about the protein before we can breathe easy (this goes back to the need to immunophenotype that protein as noted at the top of this posting).

* We need to look for spontaneous resolution of this secondary MGUS, because the failure of it to do so "may effect OS, but this needs further study."  So I need to monitor those labs.  Maybe it will go away.  Spontaneous implies without treatment, so there's that to consider.

And then there are the lingering questions:

* Mayo does single transplantation, without aggressive pre-transplant chemo or consolidation chemo.  What do they think -- if anything -- the implications of secondary MGUS would be for someone who went through Total Therapy?  If it's the immune system rebuilding, then there should be no difference -- but if it's something else, there could be a difference.

* I've spoken so far with two doctors about this, other than BB.  GT says I should discontinue Velcade as whatever is left is resistant to it, and that he doesn't know if this protein is bad and needs to learn more first.  Dr. PR, a colleague of Dr. KA and a very prominent doctor, says I should resume Velcade and Revlimid (he modified this after I explained my secondary cancer) and had no opinion on the protein.  Disconcerting that neither could assuage my concerns, and disconcerting that they had opposite perspectives on resuming Velcade.

* Most disconcerting: BB's comment that he doesn't know what this means.

There is more research to be done.  Two papers referenced in the Mayo paper are key.  The first is from  2010 and published by a group of doctors with whom I'm unfamiliar and its title ends with "...a matter of undetermined significance."  Their attempt at a clever self-referential play on words doesn't help resolve my unease.   The second paper is much older -- from 1989.  It is likely overtaken by more recent research, but it may be at such a fundamental level that it could be useful.  It is titled "Monoclonal and oligoclonal gammopathy after bone marrow transplantation."  We know (and BB is confident) that oligoclonal gammopathy is a positive thing -- if monoclonal gammopathy in that same content is a positive thing, it will be helpful.  But again -- why is BB not seeing this at UAMS, with all his transplant patients?

That's enough hardcore science for the day.

I've requested a phone consult with Dr. VR at Mayo, who was one of the authors of the study.  In my limited experience, Mayo doesn't do phone consults but as this is such a specific question, perhaps they will make an exception.

Onward.  I have renewed focus!

Well, well, well...five years passes.

Yesterday was the five year anniversary of my diagnosis.

I had had my bloodwork come back and the doctor had said that "everything is pointing to MGUS" since I had proper red, white, and platelet counts, calcium was okay, B2M was okay, albumin was okay.  Other than the M spike which elevated my protein, it looked like it wasn't Myeloma.

My dear friend Dr. BM had told me that people die of Myeloma and this was a terrible thing and even MGUS was bad.  Dr. SH, the hematologist, had laughed this off and said not to worry and don't be silly and all that good stuff.  So I wasn't as concerned as I might have been.

I had met at UCLA with the Director of the Jules Stein Eye Institute earlier that day.  My daughter has a genetic condition with her retina that has left her with poor vision that cannot be corrected with glasses and I was trying to get involved in some capacity.  A friend who has some influence with that organization made the introduction and I was thinking I would go there to discuss being on the Board of Directors for the Eye Institute.

The Director there didn't see it the same way (no pun intended but hey, that's pretty funny).  I left there with his suggestion to drive around bad neighborhoods in LA in the "Vision Van" and encourage gun-toting gang members to get their eyes checked once every two years.

This was not what I had in mind.

I left in a rather poor mood, having wasted my time and been somewhat humiliated in the process.  I was driving to my house.  It was a sunny afternoon.  A graduating student from Harvard Business School was being recruited by Disney, and my colleague EP and I were on the phone with him convincing him to join our group when my call waiting kicked in.  I saw it was Dr. SH's office.  My heart started racing, and I dropped off the work call with my apologies.  I said a quick little prayer and picked up the call.

Dr. SH said "I have the bone marrow results back, and it looks like you have Myeloma."

I was shocked.  Numb.  This was supposed to be MGUS.  I can't remember if I asked if it needed to be rechecked, but I think I did ask.  It did not need to be rechecked.

"Am I going to be alive in five years?"

"That's a difficult question to answer."

REALLY?!?!?!   Two days earlier it was a joke when I relayed my friend's concern, and now all of a sudden he can't tell me if I'm going to be alive in five years?!?!?!?

He continued.   "I want you to come in on Friday [the 15th, I believe].  You will be my last patient of the day so we will have plenty of time to discuss options."

I called my wife.  We were both in hysterics.

And that began this journey in earnest.

I considered posting yesterday -- but I thought not posting would send a message.  Yeah, it's been five years.  Yeah, I'm past the point where that particular doctor couldn't confidently say I'd still be alive.  Yeah, I'm still in complete or near-complete remission.  All good stuff.

So to drop everything and post yesterday would have been acknowledging too much to the disease.

I still have to respect it, unfortunately.  I still can't confidently dance around, laughing in its face.  It could still come back and if it comes back, the results have not been good.

BUT...I found a doctor that believes he can cure the disease.  I went through aggressive treatment.  The disease has been gone for over four years.  My recent tests, while inconclusive on blood, are highly promising on bone marrow.  We'll see where we are in January.  I also want to have a conversation with Dr. R at Mayo, who wrote about this "secondary MGUS" condition that it appears I have.  In their research, they don't understand causality or the prognistic value, but they have seen the late-emerging secondary MGUS is associated with significantly greater OS.  At it was seen in about 15% of the people they studied.   It bothers me that Dr. BB hasn't seen enough of it to immediately recognize it in my biology and to assuage my concerns -- but we'll tackle that when we can.

Meanwhile, I'm here.  I've adjusted to the "new normal."  Yes, there are issues -- I'm not sure I'll ever get 8 hours of sleep on a consistent basis again.  My GI tract doesn't work as well as it did before I got cancer.  I'm missing a chunk of fingernail (and a bit of finger) from the tip of my right index finger and it's unpleasantly numb when it touches something, like somewhere between a foot falling asleep and a funny-bone being hit.  And I tire more easily than I used to.   And then, I must admit, there's chemo-brain...which has had more of an impact on my career than the rest of my life but which has been an issue.

All this said, as I pointed out, I'm still here.

And that, really, is what matters.

So on this five year anniversary plus one day, to the newly diagnosed: there is hope.  In fact there is even more hope today than there was five years ago.  To BB and company, THANK YOU THANK YOU THANK YOU for saving my life.  To SH, my diagnosis hematologist, THANK YOU THANK YOU THANK YOU for being open-minded enough to mention BB to me.   I'd like to also thank my caregiver and wife, Jill, the other doctors that have weighed in with their opinions and help (both formal and informal) over the years, and to the wonderful friends and followers I have on this blog, and my fellow patients in a broader sense.

And as far as five-year anniversary comments to the disease...well, Myeloma, you can go !*&&)(*!@#! yourself.  :)

Five years ago today, my first detailed blood test for Myeloma

I remember going to the hematologist, who had told me that I could have MGUS or Myeloma but that it was very unlikely that somebody my age would have the latter.

He told me I needed to have a bone marrow biopsy done, and I didn't want to do it that day.  It was a Friday, and I scheduled it for Monday.  Little did I know that would be the last weekend that I didn't worry about this stuff.   How silly that seems -- to have not worried!  But at the time, both my primary care doctor and this hematologist downplayed the likelihood that I had Myeloma, and downplayed its severity.  No need to be alarmist, I suppose...

Five years...the first of several posts on the topic

I'm sitting at my desk right now.  It's a sunny October day in southern California and the sun in streaming in.  The desk is a pipe of papers.  The scene is very much like it was five years ago.

Five years ago, essentially to the day, my primary care physician called me to tell me that he observed high protein in my blood.  I had no idea what it meant.  I'd been on a moderately high protein diet for some time, was that what he meant?  No, he said.

I'd been on Lipitor for some time for genetically high cholesterol.  I don't like needles (irony alert) so I'd avoided the required blood test for about a year.  Lipitor is hard on the liver and to make sure everything is still working, they want blood every 90 days.  I'd avoided it as long as I could, when my primary care doctor told me I had to man up and get the blood drawn or he wouldn't renew the prescription.

I went in, they did bloodwork.

Two days later he called me back to give more blood, only saying he wanted to run one test over.

Two days later he called me back to tell me about this protein.

He said it was unlikely, but it could be one of two things.  One is called MGUS.  And he said it was VERY unlikely but that it could also possibly be something called Myeloma.

I said "anything that ends in Oma is bad."

He chuckled.  He said "it's a malignancy of the blood, but not like Leukemia or anything like that."   To rule that out and just confirm that this was nothing (or MGUS at worst) he wanted me to see a Hematologist.  I made an appointment.

I was still blissfully unaware.

That night I called my longtime best friend Dr. BM, who was considerably more concerned.  He said people die from Myeloma.  That didn't sound very good at all.  But I wasn't worried.

Silly me.

More to come.

But...five years later, here I am.  In complete remission (we think...that stupid marker in my blood has me nervous even though there is other data that says I shouldn't be).  Surviving.  I've been through a lot.  The treatment has derailed my career, if only (hopefully) temporarily.  It's left me tired, poked, prodded, and more familiar with the inside of a MRI machine.  It's gotten me up close and personal with those needles I didn't care for -- and still don't.  I've learned what I can from it.  I'm still here.  But all in all, this has really, really sucked.

I guess we call that perspective qualified optimism.  It's the best I can muster.  My frame of mind relative to pre-diagnosis is hard to put a brave face on.  My frame of mind relative to diagnosis and prognosis, I assure you, will be more positive.

Interesting reflections.  And more to come.

Interesting publication on benefits of transplant

I rarely re-post other articles -- there are other blogs for that sort of thing.  But this one struck me as important.

There has been considerable debate about whether or not novel drugs alone versus novel drugs plus transplant would achieve the same outcomes.  Dr. Berenson in Los Angeles, to name one vocal proponent, believes this to be the case and that there is no benefit from transplantation.

I've not dug into this study other than to read the abstract, but it does show that overall survival and progression-free survival were both superior when transplantation was part of the regimen.

Bear in mind, as well, this was a single transplant.  Tandem transplantation should be superior still, if in fact this data is accurate.

Food for thought.

Note: some considerations with respect to the study: we don't know if the non-transplant patients were transplant-eligible, we don't know if the type of disease (IgX, kappa vs. lambda, and most importantly risk assessment) was evenly distributed, etc.

Still, while maybe not as statistically significant as we'd like, it's at least a data point, even if anecdotal.

I will likely ask Dr. Paul Richardson about this on this week's CurePanel talk on the 24th of this month, where the topic is "To Transplant or Not to Transplant."  If you have any questions you'd like me to ask, please let me know!

The Strep That Wouldn't Die, and other stories. Or other story. Or question, really.

So after being symptom free for a few days I woke up yesterday with a painful sore throat again.  Took a Vicodin immediately, and a Tamiflu, and a Keflex.   Went to my morning workout.

Then I felt nauseous.

Great, I says to myself, I says.

I called my primary care doctor and told him what was up.  I didn't know if I got the same thing AGAIN, or if I didn't get rid of it the first time, or what.   I got in to see my doctor a few hours later.  Supporters of the ACA, remember that sentence in a couple of years -- you probably won't see it ever again.

I digress.

Anyhow, the doctor thought because of the stomach issues I originally had that it was probably a virus, but he did a swab for strep anyway.  Told me to see what happens and go back on the Keflex.  He was surprised that it had responded as quickly as it had before, and this, too, led him to believe it was a virus.

Long-story short, it was strep.  Probably stuck around because I didn't take the full course of antibiotics.  Stupid me, took about three days worth and when the symptoms ended, I figured I didn't need any more.  THIS WAS DUMB.  Take the full course of antibiotics.  I feel like a putz because (a) I didn't get all-the-way better, and (b) those superbugs that are resistant to all antibiotics and will eat through steel and become sentient and take control of the world's nuclear weaponry and hold us all hostage unless we come up with money are being strengthened by (1) the use of very powerful antibiotics to treat stuff that would respond to less powerful stuff, and (2) people like me who stop using something before it's all the way gone.  I'm sorry world: I vow to do my part from here on out.

As for the nausea, that was likely just taking those drugs on an empty stomach and then working out.  I usually don't need food to take stuff but I think the combo of the three may have been enough to tweak my innards.  Blech.  Anyhow, false alarm, thankfully.  After two solid days last week of projectile vomiting that would have impressed William Friedkin, I'm glad that didn't come back.  Although I was kinda looking forward to dropping these last five pounds...

God bless the good people of Arkansas, including BB and BJ, who responded to my email immediately and were prepared to sync up with my doctor out here.  I also got a long list of tests to run on my blood which attests (no pun intended) to UAMS' thoroughness and emphasis on prolific testing, which I love. As it turns out, they weren't needed in this instance.  But I was ready to get tested for everything from Parvo (sounds gross) to salmonella to feline distemper to Gumbo Limbo virus.     The last two are not serious.  In fact that last one came from a google search I just did for "funny sounding virus names."   Turns out there are a LOOOOOOT of viruses out there, folks.   See for yourself if you are astonishingly bored.

Now, as for the other story / question.   My friend EW commented in the last post that I should get a flu shot.  My primary care doctor suggested this, too.  The traditional wisdom from UAMS is that a flu shot in my current state (or perhaps recent stake) is useless as my immune system won't mount an immune response, and that was probably true for a while.  But my CD4 count is 510 now, which means it might actually do something, and my PCP said "better to have a muted immune response than no immune response."   So I guess when flu season starts up, I'll get a shot.

Maybe.

I still like Purell and Tamiflu, personally.

How a simple cold turns into hell with a compromised immune system

Hello friends.

So there's been a little bug going around.  Seems some people have a sore throat which then turns into a cold in some people if they haven't fought off the sore throat part.

That's what happens for people with healthy immune systems, that is.

Me, not so much.

I report this not for sympathy but because it could be of value to people assessing the response of their own post-SCT immune system.

I have been enjoying a pretty healthy last few years -- I don't think I've had a cold lasting more than a day or two in two years time.  I attribute this to taking Tamiflu the second I feel a tickle in my throat.  90% of the time, if I feel this coming on and get in front of it, the feeling is gone the next morning.   Maybe twice in two years (if that) it's turned into a cold that has gone away in a couple of days.   If I feel a tickle in my chest, I take an antibiotic (usually Amoxy-Clavicin) designed to wipe out respiratory infections.  I do this because when I first had my SCT, any sniffle turned into six weeks of bronchitis.  I spent my first year sick probably 60% of the time since it took so damn long to recover and as soon as I did, I'd get sick two weeks later.

Anyhow, through use of Tamilu, Amoxy-Clavicin and more importantly Purell, I've been pretty healthy for the last couple of years.  Enough where I must have gotten complacent.

I flew up to San Francisco last weekend to celebrate my mother's 91st birthday.  I didn't use Purell and came into contact with the germs of whatever parade of deranged, disease-ridden folks had used the airline seat before me.  Without thinking, I probably ate peanuts or pretzels on the flight which means germs went from the arm-rest to my hand to the peanuts to my mouth.  That's how colds get spread.

Sure enough, Thursday night I felt a tickle.  I sourced some Tamiflu from a local pharmacy and popped a pill.  Friday morning I felt okay, maybe the same tickle.  I figured worst case it would go away in a day or two.

Oops.

Saturday morning I got up to have breakfast and after two bites of an innocent egg white omelette, went to the bathroom for some violent vomiting for about 10 minutes.  I was supposed to meet an old college roommate for a lunch or a drink so I trudged along, sat down, had an innocuous mimosa (so I thought) and a small fruit plate.  Bad idea.  More violent vomiting.

Maybe some fresh air would help.  I had a sip of water (no more food or anything else, I finally determined) and walked for a bit.  Bad idea.  More violent vomiting.  On the street.  I felt like a heroin addict.

Got a car back to my hotel.  Went up to my room.  You guessed it: more violent vomiting.

About the time that I realized this was stomach flu and not just food poisoning is around the time that my throat felt like it was being slashed with a straight razor every time I swallowed.  I'd had that feeling before once or twice in my life...strep throat.

Yep.  A simple bug that wouldn't be anything went to town on me and manifested as stomach flu PLUS strep.  I flew home and got into bed immediatley, and tried Levaquin -- a carpet-bombing antibiotic -- and that didn't seem to help.  I was having to take a strong Vicodin (the 10mg of the good stuff plus 325mg of acetominophen) every two hours just to take the edge off the pain.  I was actually considering dipping into my remaining Dilaudid -- the pain was THAT bad -- and because I was worried about the amount of acetominophen on my liver.  Before doing that, though, I called my PCP who told me that Levaquin is a great general use antibiotic but isn't great for strep throat.  He put me on Keflex and about eight hours later the pain in the throat finally abated.  This was, lessee...Monday.  I went from probably ten Vicodin on Sunday to two on Monday to none on Tuesday (I'm not addicted to opiates, thank God -- was very easy for me to not take it).   As of now, things are downgraded to a mild chest cold with no symptoms other than coughing and respiratory congestion that will clear up in a few days, I'm sure.

Not a lot of fun.

The moral of the story: be ever vigilant, and use Purell!

An idiot's guide to cytogenetic abnormalities.

This will be a curious post in some ways, because it will provide partial answers and half-truths.  Not in the sense that I'm keeping anything or being intentionally misleading, but in the sense that my understanding is not fully formed.

In keeping with the philosophy of this blog, I report things as they occur, to record my understanding of events as they happen.  Other blogs will fully research something and present it in a way that is clinically correct, but may be less penetrable and will be less personal.

So the upshot of this is to give you a glimpse into a complex topic in a way that reflects my own limited understanding at this time.  It can be seen (I hope, anyhow!) as an invitation to other MM patients to learn more about their own condition -- and also as a platform for correction and further illumination.

So without further ado...

Cytogenetic abnormalities refer to tweaked (highly clinical word there) chromosomes within one's cells (in this case, myelomic plasma cells).   A normal cell has 46 chromosomes (23 "diploids" which consist of 23 from the mother and 23 from the father).

The severity of one's Myeloma can be impacted by both the number of cytogenetic abnormalities, and the type of cytogenetic abnormalities.  Typically, these abnormalities take the place of either an extra copy of a chromosome (which results in a "hyperdiploid" -- too many chromosomes -- characteristic to the cell), the deletion of a chromosome ("hypodiploid"), or a translocation of chromosome pairs (like let's say the 4th chromosome of one pair has gone off and paired up with the 14th chromosome of another pair and vice-versa, resulting in what's called translocation (4;14).

Some of the more well-known cytogenetic abormalities include del 13 (deletion of the 13th chromosome, which used to be perceived as a high-risk trait), del 17 (which remains a high-risk trait), translocation (4;14) as noted (formerly high-risk but responsive to Velcade), etc.  Additionally, a "hyperdiploid" diagnosis (too many chromosomes) is generally a better factor than a "hypodiploid" diagnosis.  I have no idea why this is -- others may be able to inform.  Particularly SuzieRose who again knows more about this stuff than any other patient I've encountered.

I was aware that I was hyperdiploid, but didn't ever really know the extent of my cytogenetic abnormalities.  How many did I have?  They are "nearly universal" in Myeloma cells -- in fact I'm not sure how one could have Myeloma without any.

At any rate, when I was last in Arkansas, I dug through my file and took a photo of the result of the marrow analysis that was done at "baseline" -- before treatment started.

Here's what it looks like.

54,XY,+2,der(2)t(2;2)(p11.1;q21),der(2;3)(p10;q10),+3,der(4)t(1;4)(q12;p16),+5,+6,+9,+11,+15,+18,+19[cp22]/46,XY[cp8]

Yikes!  It's a miracle I wasn't staggering into the emergency room with smoke pouring out of my butt with that much wrong with me.

(pause for laughter...thank you, thank you)

I refer back to part of BB's recent dictation when he commented, in reference to my current (normal) marrow, "flow cytometry [the test through which this is assessed] was negative, and originally had shown rather profound hyperdiploid lambda light chain restricted disease."

By "rather profound" he probably means that's a long string of gobbeldygook up above, versus a short string.

I recognized only a few things in here, and I was able to determine a few things on my own, but to really make sense of this without calling a microbiologist, I reached out to SuzieRose to see if she could help decipher it.  She was kind enough to invest some time in doing so, noting that every lab reports this stuff differently.

My sole contributions to the deciphering were (1) to note that the "cp" refers to "cell population."  By looking at the two numbers, there were 30 cells analyzed, of which 22 had all the crap wrong with them that is delineated, and 8 of them were nice, pretty, 46 chromosome cells that had their act together; and (2) that the 54 referred to the number of chromosomes, so I had 8 extra copies somewhere versus a normal cell.

As a quick aside, subsequent bone marrow analyses show that after one cycle of VDT-PACE, in a 20 cell sample, I had 3 goofy looking ones exactly like the ones above, and 17 normal ones.  After my first transplant, I had only normal ones.

So, to the goofiness.

Of the 22 messed up cells, here's how SuzieRose helped me decipher it.

* When there are translocations, they leave a piece of the chromosome behind at the site of the translocation.  This is said to be a "derivative" of the chromosome that was translocated and is appreviated "der".  So in my case, I had a derivative of chromosome 2, and a derivative of chromosome 4

* Whey they catalogue the chromosome changes they pinpoint them to a specific "address" on the cell, and in this case the changes occurred at 2p11.1 and 2q21, as well as 2p10 and 3q10.   I also had a translocation of chromosomes 1 and 4 that occurred at 1q12 and 4p16, respectively.

I don't know what p and q refer to -- perhaps they are the two strings where the pairs of chromosomes are supposed to align?  I don't know.  I suppose I haven't...wait for it...been minding my P's and Q's.

(pause for groan...these are the jokes, people -- they can't all be gems).

I continue.

I gather that the first marker in a pair is the "long arm" and the second is the "short arm."  So Suzierose said I have a translocation of chromosome 2 on the long arm of p at band 11.1 and on the short arm of q at band 21.

All those plusses refer to trisomies -- an extra copy of the chromosome.  I had nine of them, of chromosomes 2, 3, 5, 6, 9, 11, 15, 18 and 19.

What does all this mean?

Not much, to me, anyhow.

UAMS uses more advanced genetic analysis to determine risk characteristics of Myeloma.  So this is interesting information insofar as it shows how mangled my marrow was and shows the impact of therapy (significant reduction after one cycle of induction) -- and if there were any high-risk signs (for example, del 17p, del 1p, gain 1q) it would be valuable to know.  But in Arkansas, the real value is from the gene array that draws upon thousands of marrow samples and can assign risk based on a profile of characteristics from studying 80 different genes.

Maybe I'll take a picture of my gene array analysis next time and try to figure that one out!  : )

Special thanks again to SuzieRose -- or maybe I should call her SuzieRosettaStone.  : )

An update, with help from a fellow patient

I have had the good fortune to connect with two fellow MM sufferers on a couple of different topics recently and would like to acknowledge both of them.

Today's thanks go to SuzieRose, aka Myeloma Cinderella.  SuzieRose and I differ on our opinions of Arkansas, BB and Total Therapy but she is a remarkably educated patient and has been extremely kind to help "talk me off the ledge" with respect to the recent lab results, as well as digging into my cytogenetic abnormalities.

I'll be acknowledging the help of another friend, DC, in my next couple of posts.  But I'd like to share what SuzieRose told me.  By the way, she keeps her own blog, which can be found here.  It can be rather technical, which may make it somewhat more challenging to approach at times, but it is incredibly well-researched.

Anyhow, in the wake of the last update, I emailed BB and told him I was concerned that he didn't know the significance of the Immunifixation results that showed a faint monoclonal band, noting that I had first reported this result several weeks ago and was told it was nothing to worry about but that it seemed this might have changed.  I reminded him I was negative for MRD, but was concerned that we were no longer confident I remained in complete remission based on his carefully-worded letter.  I asked if I should come back sooner than January for the fine needle aspirations of the persistent focal lesions in my vertebrae (again, these are not active lesions -- they are holes in the bone, essentially, where active lesions used to be).

BB and BJ both wrote back, assuring me that I shouldn't be concerned, and that they'd be reviewing my case with their colleagues to discuss, but that the MRD trumps the IFE test.

This was somewhat calming, but not as much as I'm sure they intended.  After all, if your life depends on your car working, and there's a funny rattle, and the mechanic says "I'm not worried"...well, it's still a little worrisome.

Now, I'm no dummy when it comes to this disease.  I'm a pretty smart guy and I've researched this as well as a non-biologist is generally able to do.  But I don't hold a candle to SuzieRose in this area.  She is the most informed patient I've ever come across.  So I emailed her to ask her opinion about the biology of somebody who is MRD negative but IFE not-so-negative.

Her response was very helpful, citing research from three institutions that indicated that protein bands in the blood were a sign of successful treatment.  Some of this research refers to oligoclonal bands -- multiple monoclonal bands that appeared in my blood in the months after my transplants and which BB at the time said were consistent with profound remission.  However, my current bloodwork doesn't say that there are multiple monoclonal bands.  It says there is a faint monoclonal band that may or may not be the original protein.  So I wasn't going to get any comfort from that.

On the other hand, some of the research indicated that a "second MGUS" of sorts -- a single abnormal protein -- can also emerge after treatment.  And further, this research notes that this cannot be interpreted as disease recurrence, but in fact may be consistent with "eradication" of the disease.  I rather like that characterization.

So for others out there who may find this type of signature in your blood, take heart.  I'm still spooked, of course, and probably will be until the remaining lesions have either fully resolved (more on this in a future update...some doctors don't think they ever resolve) or at least until the marrow from each is tested for MRD and is negative for myeloma.

That said, the research that SuzieRose pulled together for me that references the monoclonal bands was comforting, and is recounted here:

MAYO:

... during the course of MM, new monoclonal gammopathies of an isotype (heavy and/or light chain) distinct from the original MM can emerge.17^,18 This entity, termed secondary MGUS,17 has been hypothesized to be caused by recapitulation of early B-cell ontogeny after stem cell transplantation (SCT).18 Previous investigations suggest that the appearance of a secondary MGUS is associated with better outcome.19^,20 We studied the frequency, characteristics, and natural history of secondary MGUS in MM.

"we have shown by ASO-PCR and sequencing that oligoclonal serum Igs post transplantation is not caused by myeloma related clonal B cells but rather by the regenerating B cell compartment, indicating that the oligoclonal serum Igs post transplantation can not be considered as a sign of relapse of the disease."

Australian Group

"Thus, the initial development of APB (abnormal protein band) appears to be associated with marked reduction in the malignant plasma cell clone as evidenced by the achievement of complete remission and may be a surrogate marker for myeloma eradication.In summary, the development of small APB post-transplant in patients with myeloma is common, appears to have no adverse clinical significance and cannot be considered a sign of disease relapse. "

I'll post again on how SuzieRose helped me understand the incredibly complex lab report that described the cytogenetic abnormalities (i.e., things wrong with my cells) in my bone marrow at diagnosis.

From the Doctor's mouth...

Every time I think I don't need to worry, I find more to worry about.

In the wake of last week's little goof-up with the remission terminology, BJ wrote to advise me that the people filling out those forms don't know the difference between the two diagnoses and I shouldn't worry about it, but instead should focus on what BB says and does.

He did say, via text, that I had not lost remission.

Reading his clinical notes from my last visit, though, there's enough here to create low-grade unease.

As always, he dictates his notes in a letter addressed to all my doctors in LA on which I am copied (this is routine and a wonderful aspect of what BB does).  I am reminded that my doctors in LA -- SF, GD and especially RV -- constitute a pretty darn good team as well, alongside BB.  Anyhow...the salient points:

"I am reporting to you on nick who has IgG lamba myeloma in complete remission..."  so far so good.

"Immunofixation analysis [this is sensitive blood work] suggested that the original IgG lambda band might still be present and I am going back to a March investigation when this was not hte case and I am not sure about the implications."

No longer very good.

This is the thing that I saw in my blood more than a month ago when I was told not to worry about it.  By BB, BJ and CR.  BJ again said not to worry about it when I asked her before leaving the clinic the other day.  It seems like I'm "not sure" if it's a big deal or not...that's enough to justify a bit of worry.

Then, some good news.

"The bone marrow examination dated September 4, 2013 showed no morphological evidence of myeloma...No MDS changes [this is good: don't want MDS, which is pre-leukemia, essentially, and which Revlimid can impact].  The MRD, or minimal residual disease, test was again negative."

Fine and dandy.

"The DWIBS [a type of MRI] study by MRI showed again sub centimeter focal lesions remaining in thoracic spine and pelvis also noted on dedicated STIR weighted image analysis [another type of MRI] of the axial skeleton showing 1 cm lesions at T2-4, T10 and T12.  No focal lesions in the pelvis."

These are a frustration, but by themselves would be no big deal.  However, here's the upshot.

"Thus, the patient appears to continue in complete or near-complete remission of IgG lambda myeloma qualifying for MRD negativity with persistent FDG non-avid focal lesions on MRI."

Worried emphasis mine.  These are not confident words, and BB chooses them carefully.

The clinical follow-through is as I have explained:

"I would like to see the patient back here in January 2014 when I would like to perform fine needle aspiration examination from at least 2 or 3 of the persistent focal lesions...and I would like to resume Zometa at 2 mg monthly."

I have had a couple of extraordinarily helpful email exchanges with two other patients, both of whom know a lot about the disease.  The first conversation helped me dig into the abnormalities in my marrow at diagnosis.  The second provided the perspective of another doctor (GT) on these persistent lesions, thyroid issues, cure fractions and that immunofixation test.  I'll post about these topics over the next couple of days.

Lastly, for fellow patients or caregivers that follow along, I wanted to report that it's okay to have moments of despair.  I am generally pretty strong, being mindful that it's easier to be strong when you are responding to therapy.  I had a bit of a breakdown Saturday night when I read this letter for the first time.  I felt a little like I was being told not to worry when in fact there is reason for concern.  Normally BB is as straight a shooter as it comes...so I should perhaps take at face value his telling me not to worry, except that it does contradict the letter if not the spirit of this particular dictation.

Anyhow, it's okay to be weak.  Once in a while, anyhow.  Back to being strong for now.

Talk about false alarms! What a day I had yesterday...

Regular readers will know I encourage patients to learn as much as they can about their disease and their treatment.  This is, generally, a good thing.  But sometimes, when you know just enough to be dangerous, it can have unintended consequences.

Regular readers will also know that my aggressive treatment plan for the disease has been in pursuit of a cure.  Looking back five years ago (I was diagnosed in October of 2008, so at this time five years ago I had a pain in my shoulder that was a tumor and I had raging disease but no idea) I had two options, really.  Option one was to treat the disease sequentially, hoping for a good response to each successful drug cocktail, until I ran out of combinations that worked, at which point I would have drug-resistant disease and a poor prognosis.  Option two was to clobber the disease with everything at once, hoping for a cure, and if it failed I would end up with drug-resistant disease and a poor prognosis.

I went for option two and I'm glad I did.  While it has meant prolonged treatment, I have had four years of continuous complete remission this month.  And while complete remission may not mean a cure in every case, there's no doubt that there can't be cure WITHOUT it so at the very least it's a positive sign that my remission is profound.

Nonetheless, if I *lose* remission, it's a dreadful thing.  It's not the same thing as somebody who DIDN'T pursue a cure losing remission, because most people with low-risk disease that achieve complete remission in Total Therapy DON'T lose it.  Most are cured (the exact percentage is debatable and will be proven out over time).

The downside is if remission *IS* lost, it means drug-resistant disease.  And it often returns in a high-risk variant.  Oh, sure, a couple of new drugs (Kyprolis/Carfilzomib and Pomalyst/Pomalidomide) have come out in the last five years and they can extend life by a little bit but at 45, I'm not looking for a little bit.

So every six months, when I check in and the remission has sustained, I'm closer to being confident that I'm cured.  And if it's lost, then it's pretty dire.

So this dynamic, and my acute awareness of it, sets the stage for an episode of panic yesterday that thankfully has a benign ending.

After last week's visit when I wasn't able to meet with BB because his rounds had him later than usual, I was a little uneasy about those residual lesions not fully resolving yet, and the monoclonal signature in my blood which is either a sign of profound remission and recovering marrow, or a sign of return of the disease.  The fact that my bone marrow was negative for residual disease was definitely encouraging and lends credence to the fact that the blood is a non-issue, but I'm still eager to have those damn lesions resolve so that I can feel confident I've beaten this thing once and for all.

I got my paperwork Monday via Fedex and perused it.   Put me back on Zometa for bone strengthening.  Come back in January for two fine needle aspirations (of the T10 and T12 vertebrae, for those playing along with the home version of the game).   Seemed like low grade stress at most.  All tests were negative.

Then yesterday morning a dear friend called and said he was sorry to hear the news.  I thought he was taking yesterday's blog post a bit hard.

Then I found out that my wife had informed him I had lost remission.

I then calmly told my wife that wasn't the case.

Then she texted me a photo of something on the paperwork.  A tiny little check-the-box thing that I hadn't even looked at because it has been so rote for the past four years.  Of COURSE I'm in remission, right?

Except that's not what it said.  Instead, it looked like this:

Forgive the rotation of the photo, but you get the point.   The big circle around "without Remission" was the scary thing.

My wife had thought I was aware of this due to my consternation at the need for more bone marrow work and the mysterious blood results.  So she hadn't said anything to me, thinking I already knew.

I texted BB (thank God I have a direct line) and said "Paperwork says I have lost remission.  Is this true?"

I also texted his chief administrator BJ, and my PA who is named JA after my former PA (CR) moved on from UAMS to other pastures.  Sorry for the overload of initials, by the way.

While I was waiting, it occurred to me that I thought there were other places that indicated with a check box what my diagnosis was.  I called my wife and had her pore through the papers for it.  We couldn't find it.  The closest thing we could find was this, in indecipherable doctor script:

About all I can make out of that is...uh...nothing whatsoever.  In the cold light of day today, GL probably means IgG Lambda.  Then there's a symbol that could mean "with" or "without" followed by CR.  Again, in the cold light of day, what I thought was GIRD with a weird symbol is really MRD negative.   Then underneath it is a FL with a plus sign and in the cold light of day that probably means focal lesions still persist.   So, dammit, I figured it all out, a day later.  Except I still wouldn't know whether that symbol meant in complete remission or not.  And even then, they wouldn't say that "complete remission" has been lost -- they would say "remission" has been lost.  So any mention of CR has to be a positive thing.

No need to panic after all.  This could have allayed my fears.  However, dear reader, I can assure you that adrenaline was interfering with this simple analysis.

About 40 minutes after I sent my text to BB, he wrote back "Hell no."  I do love that man.  "Have I lost remission?"  "Hell no."

He confirmed it was a transcription error.  BJ later emailed me the same thing.

I was in a bit of a daze the rest of the day -- if the cancer doesn't get me, I might have a heart attack from that kind of stress!  :)

There's probably a lesson here about just living each day and enjoying it for the gift that it is.  That, too, is something that is easier to recognize when you aren't in the heat of it, believe me.

So for now, steady as she goes.  I'll be back in January to have my spine poked and that will hopefully tell us more -- unless, of course, the Zometa helps those lesions resolve fully by then.  It's worth noting that many doctors don't think these things ever go away...but then I didn't go to just any doctor.  :)

Ruminations on last weeks' tests

I try not to overthink all this stuff, really, but it's a fine line between wanting to know everything I can about my condition and the likelihood that I'm cured and what can be done to ensure that outcome, versus obsessing about it.  Generally speaking, I feel like I've done a very good job of managing this.  I don't feel or live as though I have a Sword of Damocles hanging over my head.  I don't think about cancer -- consciously -- all that much, all things considered.  I hear about people who approach upcoming tests with dread and I don't really have that feeling.  I have 10 minutes of eagerness reading through results on the day I'm to meet with BB, but other than that, I've got it under control most if not all of the time.  And part of the reason I don't have that dread, I think, is because the tests are so frequent and I am sufficiently on top of things that the "unknown" part is kept pretty well managed.

For this reason, I'm permitting myself to indulge in some "what if" thinking at the moment, based on last week's test results.

At the end of the day, if I have a thyroid problem, that's controllable with pills.  It might even explain some of the fatigue and GI issues.

Similarly, I'm not really worried about the presence of "small lymphocyte aggregates" in my marrow, because if it was something serious, they'd have told me instead of telling me not to worry about it.  While I want to learn more about this, the little research I've done indicates that it's present in a benign form in much of the population.  It's connected to lymphoma but I think it's correlation without causality and if I had other lymphoma markers, they'd be evident.

What I *am* worried about is the connection between the unresolved lesions in my bones, and the mysterious reappearance of the monoclonal signature in my blood under sensitive tests (normal tests still show that it's negative).

When they perform the fine needle aspirates of my spine and hip, they will pull marrow (assuming the sites are accessible) and analyze it for the presence of myeloma.  They last did this a year ago during the "great MYC gene scare of 2012" and the one site they were able to access at that time was the hip, and it was negative.

They did not, at that time, have the ability to run an MRD test -- the Minimal Residual Disease test there is dozens of times more accurate (I seem to think 60X) than a standard bone marrow analysis.  I haven't had the chance to speak with them about this but it's certainly possible that they may want to pull the marrow from there to run MRD tests on it.

The one marrow site they did access -- my hip, not where the lesion was but in one of the sites where the marrow is most prominent in the body -- was negative for MRD, and that's great.  If I was MRD negative throughout the body, I'd be considered cured.  The issue is that it's from one site, and marrow could be clean in one place and not-so-clean in another.  BB told me he is working on developing a test that would perform MRD on the blood, rather than the marrow, which would tell all.

But we don't have that yet, so instead I will be pin-cushioned here once we get it scheduled.

The best case: the former lesion sites are all accessible, each is MRD negative, the marker in the blood is a sign of marrow recovery rather than returning disease, and BB tells me I'm cured and can go off meds.

The worst case: one or more lesion sites show residual disease, the marker in the blood is a sign of its return, and I need to determine whether or not to undergo aggressive chemo to keep on the potential cure path -- or accept that relapse is inevitable and join folks who are waiting for more treatments to come out of big pharma.  After all, if I still have disease, it's resistant to Velcade at a minimum.

The likely case: not all lesion sites are accessible, the one or two that are are negative for MRD, we chalk the blood up to marrow recovery but deep down inside neither of us is all that confident in it, and I stay on Velcade and continue to wait out resolution of these lesions.

More news to come as events merit.  Be well, all.

An update: the good, the bad, and the ugly...

Clint Eastwood:

* My MRD test (the most sensitive marrow test they have) tested more than twice as many cells as last time, owing to a better marrow sample.  With around 3.5 million cells tested, not a single myeloma cell.  From this part of my hip, at least, there is no disease remaining.


Lee Van Cleef:

* My bloodwork under Immunofixation says "the original IgG Lambda M Protein may be present.  An in distinct monoclonal band is present in the lambda region.".  This COULD, I am told, just be the product of recovering marrow.  Of course it is also what it would look like should the disease return.

* My T4 thyroid count is very low.  Not sure what this means but it requires more testing.  T3 is normal but on the lower end of the normal range.  T4 has dropped significantly.

* My marrow, while negative for myeloma and MDS, is reported as having a "significant hematologist abnormality" called a "small lymphoid aggregate.". BJ told me not to worry about this but anything that is a significant abnormality seems definitionally to be something to worry about.  I don't yet know what it means although initial research indicates it may be present in up to 60 percent of the general population so I will see what I can learn.


Eli Wallach:

* The lesions in my spine and hip are unchanged.  As they haven't made any move towards further resolution in two years, BB wants to stick needles into each of them and test the marrow from those spots.  I suppose if they are all MRD negative, he might say I am cured regardless of the fact that they persist, but I don't know as he was running so late I didn't get to speak with him directly about this.

That means a return visit to Arkansas for more bone marrow biopsies sometime soon.


I am tired of this -- and yet mindful that many others with this disease have it far worse than do I.

On balance, then, I probably don't feel as crestfallen as Eli Wallach did when his agent called and said "they're considering you for a movie called 'The Good, the Bad and the Ugly'...the good and the bad parts are taken."

Concern allayed

I had the pleasure of having dinner (and wine!!!) with BB, his lovely wife, his irrepressible chief of staff BJ and a colleague of theirs who has recently joined in a consulting role after years of doing this with the IMF.

Among the stories, laughter, jokes and discussion of all things Myeloma, I did speak with BB about the ending of the lite arm of my study.   As it turns out, because the stated goal of the study was to reduce toxicity (mouth sores, most prominently) and because this wasn't achieved, the study was ended early by a review board.  All patients now receive the standard arm.  BB said that there were no meaningful differences in outcome and in fact depending on what cytogenetic abnormalities a given patient has, some patients fared better under the lite arm.  He said they were working to try to understand why but did not have this figured out yet.

He also told me he is working with some colleagues on a new MRD test that will seek to overcome the imitations of the current one -- primarily that marrow from one individual site in the body could be free of cancer cells but there could be some elsewhere.

All good news.

Now we wait to see if the MRI is clean, if my MRD is negative in marrow, and if the bloodwork is clean and I can write off that mysterious monoclonal signature that showed up recently.

We should know on Friday.

An unnerving update from Arkansas

I have been in Little Rock for about 16 hours, and already managed to get my pizza fix in from the always-delicious Dam Goode Pies.

Sadly, that is the highlight of the trip so far.

After early morning MRIs, the scheduling snafus began.  I am in the infusion center for my third attempt at getting labs done today.  I mention this primarily because I think back to nearly five years ago when I was running around City of Hope.  I have grown more tolerant of delays and scheduling mistakes -- I wonder how much is that I cut the good people of Arkansas slack given that they have hopefully saved my life, versus me just having mellowed.  Perhaps a bit of both.

I met with the data manager, a usually innocuous meeting that involves me updating the center here on anything of merit (for example the endoscopy, side effects, etc.) and signing some consent forms once in a while.  Velcade now has a small risk of some kind of horrible brain virus that kills ya dead. Very rare, I am told.  Nobody has seen it here in Arkansas, but it must exist.

That wasn't what troubled me, however.

I was told that the "lite arm" of Total Therapy 4 had been discontinued.  The lite arm involved one less cycle of induction (pre-transplant) chemo, and one less cycle of consolidation (post-transplant) chemo, and the transplant chemo spread out over more days versus the standard arm of the study.  The goal of doing the two arms was to see if they could achieve the same clinical efficacy (ie cure rates) and achieve less toxicity.

I was told the lite arm would not result in any less efficacy of outcome or it wouldn't be studied as it would be unethical to do so if the doctor had any reason to believe the outcomes wouldn't be as good.  So on we went and I was happy to get the lite arm as it meant less chemo.

In explaining why the study had been discontinued, the data manager said that it was because there was no difference in toxicity noted between the two arms, and the "gold standard" remained the standard arm so they didn't want to change it.  That is one interpretation.  The other is that the lite arm outcomes weren't as good.   Sadly, my money is on this as the real reason.

It is very disturbing, to say the least.

I see BB on Thursday and will ask him abut it then, if I don't see him before then for a drink or dinner.

I better not have gone through all this to have a worse outcome than if I had done just a little more.

:(

When does a negative test not feel so negative?

When instead of saying "the original protein cannot be detected", as most of my tests from Arkansas have said, it comes back "the original M protein may be present.  Multiple indistinct bands are found in the gamma region in the area of the original protein."

CR at UAMS assures me it is negative.

I do not like it, Sam I am.  If I wasn't rushed here, I'd come up with some witty play on Dr. Seuss using the words "blood" and "protein" and "monoclonal" even though no rhymes come immediately to mind with respect to any of them.

The local test said there's no monoclonal protein.  The same blood tested at UAMS comes out as above.  So UAMS is more sensitive.  Ugh.

UGH I say.

Oh well.  Probably nothing, and there's nothing I can do about it even if it *is* something.  Come September, the MRI should tell all.  If those stupid pits are gone, perhaps I can breathe a bit easier.

Curetalk panel with Dr. Kumar from Mayo Clinic...any questions?

Hello folks.

I've participated in a number of panels over the last year with various Myeloma specialists.  Thursday of this week at 7PM Eastern, Dr. Shaji Kumar of Mayo, Rochester will be discussing updates from the most recent ASCO conference, as well as taking questions from the panelists, myself included.

If anybody has anything they'd like to ask, please let me know and I'll do my best!

Meanwhile, if you want to listen, you can register for the call here:

http://trialx.com/curetalk/panels/dr-shaji-k-kumar-from-mayo-clinic-discusses-myeloma-asco-updates-on-the-cure-panel-talk-show/

These calls are typically limited to 50 participants, all of whom can also ask questions, or can stay anonymous and just listen.  These are typically pretty interesting and informative so I would encourage those who are interested to sign up.

Only a false alarm. Immunofixation negative!

So I saw my Dr. GD out here on Tuesday, and explained to him I was uneasy about the immunifixation test.  He didn't seem to get the gravity of my concern -- deep down, he still thinks it's unlikely that I'm cured so for him, seeing a return of monoclonal protein is almost expected, just a matter of when.  I explained to him that I'm going after something different, and he said he understood...but I'm not sure he did.

Anyhow, he ordered a battery of additional tests, and I had them draw some blood to send to Arkansas as well.  I'm waiting for their results, but the local lab came back with "normal pattern, no monoclonal proteins detected" under the immunofixation test.

So I'll chalk this up to either a false positive, the oligoclonal noise that BB expects, or possibly my immune system ramping up in response to a potential cold that I may have been fighting off.  Didn't feel that bad although I had a tickle in my throat and my WBC went up to 5.8, which for me is high (it usually is around 4).  WBC will be recovering now that I'm tapering off my Velcade and not on Revlimid any longer, so that could also be the cause.

In any case, until I hear otherwise, I remain in profound remission and hopefully am cured.  Still waiting for those pesky pits in my spine to resolve but we'll see how those are on imaging in September.

I may or may not share some information about a patient I've recently become friends with who was in the care of JB (the anti-transplant guy) and had unsatisfactory results...but for now, accentuate the positive, which is to say, the test is negative.  :)

Have an excellent weekend, all.

Incomplete feedback from a couple of doctors on my labs

So in the wake of my alarming little reappearance of the word "monoclonal" on my labs the other day, I did a little inquiring.

BB told me not to worry, as previously reported.  That this was an oligoclonal band and a sign of marrow recovery.  This is corroborated by that article I posted.

BJ, BB's right arm, was kind enough to follow up with a summary of the immunofixation tests I've gotten from Arkansas over the past three years.  Several (early on, though) did indicate the presence of more than one monoclonal band.  They were not the original MM protein that was reflected by my disease, though, so it wasn't a recurrence.

However, these reports have likewise been clean the last several months.

Dr. GT, a MM specialist in his own right who used to work for BB, has been kind enough to answer a few questions of mine over the last year since my friend CP, whom is in his treatment, has been a great teammate in our little battle here and she referred me to him.

GT said that without knowing which specific protein (both light and heavy chain) this is, it's impossible to say whether or not it's a recurrence of the disease.

Which brings me back to the Arkansas comment that seemingly indicated my original monoclonal issues had both a light and heavy chain component, and since the light chain is the only one that was found here, that's another indication that all is well.

But unless Arkansas sees the detail behind the protein and confirms it's not the same, I won't be convinced.

So I'm going to get some blood sent to Arkansas the next time I'm back at the doctor's.  I'm supposed to be sending it to them monthly but I must confess, years of complete remission and a growing confidence (interrupted by a few crises of faith) that I'm cured has led me to be a bit cavalier about so doing.  I resolve to be better about this going forward.

The likelihood is that this is either (a) a false positive reading or (b) oligoclonal.  That said, as I wrote above, I'll still be trepidatious until it is confirmed.  Until then...I shall try to put it out of my mind.

Another false alarm?

The Iron Law of Oligarchy.

I remember literally nothing else about a class I took in comparative political structures of developing nations during my junior year at UCLA except the professor's name (Edward Kannyo...I just looked him up and he's still kicking around, writing articles about post-Gaddafi Libya) and the fact that we read some book called the Iron Law of Oligarchy (or, rather, were supposed to have read it).  I just knew to throw that phrase around once or twice in a paper.  Somehow I did well in the class.  Hmm.

I should have been studying microbiology, instead, it seems.

Oligo = numerous, mono = one.  Oligarchy is rule by a few, monarchy is rule by a...wait for it...monarch.  One.  Oligopoly is control by a few, monopoly is...well, we all know.

Oligoclonal means several bands of duplicated protein.  Monoclonal is one.  One bad protein, reflective of cancer.

If monoclonal proteins show back up for me, it means the whole attempt at a cure is obviously shot, and more depressingly it means the disease is most likely drug resistant and high risk in its profile, given the experience in the still fairly low (less than half) of low-risk, newly-diagnosed MM patients that relapse under Total Therapy 3 (or 4, its successor therapy) at Arkansas.

I would, needless to say, not like to see a return of the monoclonal protein.

When one is recovering from a transplant, it is not uncommon to find oligoclonal bands in one's blood or urine.  This is actually a sign of a recovering immune system, and is in fact consistent with remission and the natural healing of the body.  Here's an abstract from the NIH on the topic.

I had this when I was first in remission, and it was noted for maybe six months.  Then, nothing.  Not a trace of anything untoward in my blood, for more than three years.  Good stuff.

Imagine my dismay, then, when yesterday my labs from two weeks ago were ready and there was no monoclonal protein in my blood under SPEP (Serum Protein Electro Phoresis, a relatively blunt instrument relative to the other tests but still capable of detecting low levels of monoclonal protein).  However, under the more sensitive immunofixation test, the following result came back:

Faint monoclonal lamba light chain observed in the gamma region.

That's not good.

I had IgG lamba myeloma.

Of course I immediately texted BB and reported the precise wording of the test, including the fact that SPEP was negative.  I ended my text with "should I be concerned?"   This is kinda like the Hindenberg reporter saying "uh, looks like sparks up there, hope it all works out."  In other words, I was already quite concerned.

The next fifteen minutes were pretty tense.  Thankfully, as busy as BB is, he checked he cell phone and within fifteen minutes he wrote back:  "No.  Oligoclonal."

Now...this MIGHT be the case.  It could simply be that the one band is so faint that others which could be there are even fainter.  It could also be that as a light chain (my light chains are normal and the ratio is in balance) versus blood, it might not be anything to be concerned about.  And I did a scan of the Internet and found a site where a doctor said that such a signature was, in fact, nothing to be worried about.

That said, it scares the crap outta me.

I tested negative for any disease with the extremely sensitive MRD test in Arkansas in March -- that's about 60 times more sensitive than immunofixation.  And my marrow was clean as a whistle.  So I'm probably worried about nothing.  Maybe, when I get my next test results back on or around the 23rd of the month, it will show nothing, again, under immunofixation.  It might be a plain ol' false positive, after all.  I've had friends with false positives for this disease.

But like I said, it scares the crap outta me.

Not much I can do other than wait it out and stay strong.  I am once again humbled by the bravery of those patients who struggle to stay in remission and watch their disease progress -- I have very little to complain about.

Have a jubilant Independence Day!