Stupid lesions have not yet resolved. : (

I am currently awaiting my bone marrow procedures, which will include three pulls, I think -- the standard bone marrow, the gene array (which I may yet veto) and a new test for Minimal Residual Disease.

Since I make them knock me out for this with propofol (the Michael Jackson sleep drug) I was getting a pre-op consult with one of the physician assistants here.  He was kind enough to pull up my MRI -- they have new software which allows you to scroll through your body bit by bit -- it was fascinating to see!

Less fascinating was the tech's write-up, that indicated "stable small lesions are observed in the thoracic spine and pelvis."  I'd never seen one in the pelvis before -- that was troublesome.  However since it's characterized as "stable" it must have been there before.  Perhaps just not on the last MRI for some reason?  I didn't recognize the name of the tech so it may have been somebody new...generally they like to have the same tech read the scan to ensure it's done consistently but it's now been five years of coming here, just about, and personnel change.

I saw BB at dinner last night and he noted that he has new talent coming in...he's lost some doctors who have moved on to private practice but he's retained his research specialist and one of his former doctors who moved on to work for doctor GT in Utah is coming back here, which is nice.  I mused that he's a bit like a Head Coach for a top football team whose assistant coaches are constantly being poached or lured away by other jobs.  Talent recruitment and retention is a big part of his job.

At any rate, there will be more to review and discuss about these persistent lesions tomorrow.  It does mean there's probably no end in sight for the Velcade.  And depending on what the MRD test shows, I'll either view it as an inconvenience or a critical necessity.  Or perhaps I might even need to switch to new drugs if there is residual disease.

Greetings from Little Rock

Boy, is it cold here...and rainy.  I'm currently hunkered down in the 8th floor of the cancer center, which is where the entire Myeloma team moved about six or eight months ago.  They've got a couple of computers here so I thought I would avail myself of the Internet connection and update you folks.

There's not that much to report just yet, other than the blood draw went off without a hitch for once (this means they knew to expect me on the 4th floor at the infusion center rather than at the blood lab on the 1st floor).  I had found the little topical freezing spray that my local oncology nurse had given me and a little spritz of that led to a painless port access.  I came back an hour later for a lab printout and everything that's back fromt he labs looks good -- the cancer markers will take another day or so but I'm anticipating everything will be consistent with complete remission.

The PET machine was out of service so my 9:30AM PET scan has been rescheduled.  They gave me the choice of 5:30PM today or 5AM tomorrow morning.  Astute readers will likely guess that I chose the former option.  Still being on West Coast time, even this morning's 7AM wakeup call seemed brutally early.  4AM is not in the cards.

I briefly visited with the irrepressible BJ, BB's right hand.  The visit was enough to answer a couple of questions I had about a new test, the Minimal Residual Disease test which is being done in conjunction with a group in Salamanca, Spain.

The link below addresses a study wherein this test was used to identify those "high risk" myeloma patients that lost remission versus those who did not.  I've not read this carefully enough to paraphrase it here but perhaps I'll do so at some point soon.

http://bloodjournal.hematologylibrary.org/content/119/3/687.long

The second link talks about which of the two tests is more accurate, and what a typical measurement is.  The lowest measure was .001%, or 1 cancer cell in 100000.  The median was 14 cancer cells in 100000 and the high was 1100 cancer cells in 100000.  Notably, everybody in the study was in complete remission.  So some of us with complete remission could still have 1 cancer cell in 1000 cells.

http://www.haematologica.org/content/90/10/1365.short

In this study, they also establish the threshold of "minimal residual disease" being 10 cancer cells in 100000 (.01% cancer cells).  It seems like a subjective threshold, clearly, but it does serve a comparative purpose for test sensitivity.

I was told by BJ that the MRD test at MIRT is sensitive enough to detect one cancer cell in 6,000,000.  It's a bone marrow test using some type of flow cytometry but I recall BB telling me something about an "8-way color array" (this is almost certainly wrong...consider it a placeholder, perhaps referring to the "multiparameter flow cytometry" that the first link above mentions).  In any event, I shall be paying keen attention to the results of that test.

I'm off to the next appointment.  More when events merit and time permits.

Part 2 of the statistical update

I'm so sorry, folks, to be behind.  I've received a number of terrific emails from the newly diagnosed to long-time fellow travelers and I want to thank all of you for writing to me.  I'm particularly thankful, always, to hear from patients who have found this blog to be helpful to them as the lead their own fight against this disease.   You inspire me and I'm thankful to play any part whatsoever in your battle.

So...where was I...

Ah yes, the lack of a plateau.

I sent BB a lengthy email explaining my concerns, and the basic math that I'd done on the back of an envelope to arrive at somewhere around 50-60% cure versus 87%.   He commented quickly in an email that the 87% figure had been updated as a result of longer follow-up, and that this is expected, but that the Blood article (from which I presented figures below) indicated that "cure is still there."

It's a question of what percent.

He told me, in his playful way that has a serious undercurrent, that I was "doing a lot of arithmetic that was not really getting anywhere" and that I was a bit of a "pain in the ass."  :)    I know this is an endearing term from him so I relish it.

It is a huge testament to this doctor that, despite not having an appointment with me scheduled, he called me and spent 45 minutes not just discussing this data but also forwarding me articles, both published and unpublished, to help educate me.

He agrees that the final number will be somewhere better than TT2-Thal, but not the 87% that looked like could be the case.   The numbers for TT4, which include more extensive maintenance than TT3 (the beginning of TT3 used only one year of Velcade, for example), are better than TT3, so the current cohort can be expected to do marginally better.  BB has never in his career seen a decline in efficacy as therapies advance -- recall that in all the studies for pediatric leukemia as well as the TT regimens, the curves move up the Y axis towards the top of the graph as they advance.

The real answer is, we won't know until 10 years out where the final curve is.  He also reminded me, as did a couple of blog followers, that these curves include mortality from other causes so you have to take those out -- doing so flattens the lines significantly, though they still don't reach a plateau yet.

I was casting about for something that would give me slightly better news on this, and BB was kind enough to tell me that they have compared PET scans after the commencement of treatment with treatment outcome.  Before treatment begins, a PET scan is performed to identify the number and intensity of what are called "FDG-avid lesions" -- thriving cancer tumors.  Then, after the first week of treatment, another PET scan is performed to see the impact of the treatment on patient biology.  These same tests are done with MRIs, as well.

I've got some data to share, but presenting it is going to take some time, so I'll get back to that tomorrow.  I will say that the news is slightly more optimistic than the 60% figure.  Not 87%, but something.  :)

Lies, Damn Lies and Statistics.

A targeted Google search (perhaps one of this blog's contents would do the same, of course) reveals that I already used this header back in 2009, and yet that turn of phrase (whether from Benjamin Disraeli or Mark Twain) remains meaningful.

Before I jump in, though, let me say that if anybody missed yesterday's Curetalk broadcast and wants to listen to it, the link is right here.   It's four panelists with Myeloma, myself included, answering questions from patients about various aspects of treatment and side effects.

Now...to the matter at hand.

I've been contemplating for a few days how to address this.  It's fairly significant news and it's not good.   It's not about me, personally.  I remain in complete remission.  But it is sobering because of what it might mean for me down the road.

The upshot is this: we now have a longer follow-up period of data from UAMS on the survival curves of patients treated by the TT3 regimen.  And while the survival curves are still very impressive and while many patients are being cured, the cure rate is not what we thought it was.

Long time readers who are into these types of details will likely remember two curves that show the percent of low-risk patients who have achieved complete remission that have maintained this remission.  Or put another way, it shows the percent of patients that lose remission.

Figure 1

The blue line shows low risk patients in TT3 that have kept remission or near complete remission (this includes those patients who have a very low "MGUS" type residual level of the disease -- recall that MGUS exists in over 3% of the general population over 50 and is oftentimes meaningless).  The red line shows low risk patients in TT2, which used a different protocol and didn't have the advantage of Revlimid, Velcade or even Thalidomide in one of the arms.

You can see that after six years, the red line of TT2 has "flattened out" at around 45%.  This type of flattening out is the core principal of Total Therapy.  It was first observed in treating childhood leukemia (ALL) at St. Jude's over a period of several decades.

To explain the significant of this chart, I'm going to take a step back historically.

Figure 2

So you can see from Figure 2 here (which are the trials done at St. Jude) that a flat line exists -- that's cure.  If you get to the flat line in the curve, the disease does not return.  In the simplest terms, you can see from the yellow line (studies 1 to 4) in figure 2, after 15 years, nobody lost remission.  And really, after 5, very few people did.   Over time, the percentage cured increased and the therapies became more effective.  By the time of studies 11 and 12, about 70% of people were being cured.  By the time of study 15, the projection was that around 90% of people were being cured.  All good stuff for a disease that used to be considered incurable.

On the basis of this work, TT for Myeloma was pursued.  Over the years, it, too, has established curves that look similar to the progress of ALL.

Figure 3

So here, you can see the progress made from TT1 (which looks like a cure rate of about 17.5%) to TT2 with thalidomide and TT3.

Now, along the way UAMS developed a means of testing bone marrow to assess whether or not one has "high" or "low" risk.  About 85% of people have low risk, 15% have high risk.  The graphs in figure 3 include all patients.  But here in this next chart, we see the results of TT3 on those with high risk (red) versus low risk (blue) disease:

Figure 4

You can see the folks who are unfortunate enough to have high risk disease are not able to remain in remission very long.  While a large percentage of the people with low risk disease DO remain in remission for a long period of time.

All of this information was published in a document called The Myth of Incurability which was presented by Arkansas in late 2007 or early 2008, I believe, shortly before I was diagnosed.  At the time, they were about four years into the TT3 protocol.

I'm beginning to feel like this guy.

Bear with me, dear readers.

So far, so good, right?  I went and got tested, I'm in the blue group, I went through TT4 which was like TT3 but less toxic because TT3 was believed to be so effective that it couldn't be improved upon.

All's well.

A couple of years later (fall 2009, just as I was finishing my transplants) a new document was published and presented.  In this one, called Modeling for the Cure, we saw even better outcomes.

More information was available from the TT3 trial.  Figure 4, shown above, was updated.  And it was more fantastic news!

Figure 5

Notice here, the line in blue is FLAT at around 4 years.

The poor high risk folks continue to lose remission, while the low-risk cohort has plateaued.

This, my friends, is the chart that I have followed meticulously for the past three years.  I achieved complete remission in September 2009.  I'm approaching four years and all looks good (save for the lingering pits in the spine which I keep hoping will go away).  In fact, temporally speaking I have reached the plateau in this graph.  I'm cured.

Awesome.

On the basis of this data, UAMS used some standard statistical tools to forecast the "cure fraction" of these patients.

Figure 6

Here, the green line shows low-risk TT3 patients that have achieved CR or near-CR.  That's not the whole group.  But I made that group, and there looks like a plateau, again, at four years.  It hasn't been absolutely reached here, but it certainly looks pretty darn close and according to these common statistic tools, 87.6% of patients can expect to be cured.  The P statistic is a measure of "confidence" in the forecast -- a P of .0001 is very, very good.  In other words, this 87.6% is, statistically speaking, a number in which we can place a lot of confidence.

That is, if every curve behaves as they have in the past.

Meanwhile, more time goes by, and the numbers continue to look good, leading to the publication in a periodical called Leukemia in 2012 (love these periodical names: Leukemia, Blood, etc.).  In this publication, which can be found here, the numbers look great, still, but the goalposts have moved just a smidge.

Figure 7

Now I've got some color issues so I frankly couldn't even tell you what line to look at by color, but it's the one on the top.  That's TT3.  "Landmark" refers to four years after achieving CR -- that's the point where the plateau was observed in Figure 6, above.  Essentially the assumption is made that between treatment related mortality and disease recurrence, that stuff gets out of the way in the first four years according to previous work, so we can now measure from that point.

Some salient observations:

* It takes a long time to see where the TT1 plateau is reached.  It's not until around 11.5 years after the four year mark, or 15 years from the onset of CR.  That's pretty close to what we observed in Figure 3, above, so that makes sense.

* TT2 plus thal appears to have reached a plateau a bit earlier and much higher -- it appears to be leveling off at the 6 years post-landmark point.  It was a little early to see this on Figure 2 but Figure 2's data shows the beginning of it tapering off, so that comports well with this chart.

* TT3 looks very good...94% of people are still estimated.  So the 87.6% number from figure 6 isn't quite as good...it's 94% of that figure, or 82%.  In other words, 82% of low-risk patients achieving CR under TT3 are cured.  And since I've made it to the landmark, it's 94% chance that I'm cured.

According to this data.

Now the other shoe drops.   Here's where I would be tempted to end this post and make it a cliff-hanger, but I won't be doing that.  :)

A fellow patient, blogger and friend of mine, Gary Petersen (who was also on the Curetalk panel with me), was recently given new survival figures from UAMS.  And they are very good!  Take a look at this, for example:

Figure 8

So here, you can see that after 9 years of enrollment in TT3, including both high and low risk patients, and including both those and have achieved remission and not, about 70% of people are still alive, and about 55% or so have not seen their disease progress.  That means about 79% of people that are still alive have not relapsed.  Bear in mind, this includes death from ALL causes, not just Myeloma.  The National Cancer Institutes data is only 19.6% alive after 9 years -- so UAMS is more than 3X that good!   All great.

So I excitedly reached out to my friend Gary Petersen and said "I bet the numbers are even more impressive when you split out low risk from high risk."

Here's where things get not so great.

Figure 9

This shows overall survival with 9 years of data, now.  Again, this is all deaths, not just myeloma.  So both the curves fall off faster than would be the case if we just looked at Myeloma.   Nonetheless, you see a plateau for the high risk patients, but it's a straight line down for low-risk patients.  No plateau.

The next chart shows progression-free survival -- meaning no disease recurrence.  We expect this to be lower numbers than overall survival, obviously, since some people might have experienced a loss of remission but not have died yet.

Figure 10

Here, again, the red line of high risk patients plateaus.  But there is no plateau in the blue line.   I repeat...no plateau.  In the immortal words of Scooby Doo...

RUH ROH, RAGGY.

Or, in English...sh*t.

Which brings us to the next piece of data...for those who achieved complete remission, what percent have maintained that remission?   Recall (or simply use the "page up" or scroll bar here) in figure 1, for ALL patients (including high risk) this number looked to be in the high 80s and looked headed for plateau.  In figure 4 we hadn't seen a plateau yet but the number was in the high 80s.  In figure 5, we saw a plateau at four years that pointed to 90% of people not losing remission -- being cured.  This led to figure 6, which showed with a high degree of confidence that there was a plateau at 87.6% of people being cured.  And figure 7, with a couple more years of data, supported something close to this (82% maybe instead of 87.6%, but still 82%).

But now...

Figure 11

There's no plateau at all.   What looked like a plateau from about years 3-5 was a false plateau.  Remission losses resume again shortly thereafter.  In fact, six years after complete response shows only 76% of people are still in remission and it's ticking down at a steady rate.  You can see where it looks like it's going to flatten off...only to resume again.  I've never seen anything like it before in 20+ years of looking at data for a living.

Regardless, the medical import of this is fairly clear: we have moved beyond "Ruh Roh, Raggy" and directly into "ZOINKS!!!" territory.

ZOINKS!

(Interestinlgy enough, when I searched the web for this pic, it found it, ON MY OWN BLOG, haha...must've used it before somewhere).  Anyhow, it is fitting.

Zoinks, indeed.

Naturally, this updated statistical news went over a bit like a turd in the punchbowl at my prospective "victory over Myeloma" banquet.  

So, what can we assess from all this?

Well, we know that the outcome isn't gonna be any worse than TT2 with Thal was, and that stands at an overall cure rate of 45% for low-risk Myeloma.

While TT3 remission loss appears to be lower in the interim, we might end up at the same end state.

Which leads to the potentially REMARKABLE counter-intuitive conclusion that the new drugs in which everybody holds such promise -- Velcade and Revlimid -- might not be curing anybody whatsoever, and the cure could simply be coming from PACE and Melphalan, same as 10 years ago, and all the novel drugs do it keep remission longer.

Ugh.

Now, that's the worst case scenario.  Bear in mind, also, if somebody falls in a manhole or is stuck by a meteor (no offense to our Russian friends) they are included.  So the curve should be flatter.  Maybe the cure rate is 55%?

55%, for those playing the home version of the game, is not close to 82%.

Moreover, since the remission loss appears to kick in earnestly after about 5 years after CR (1 year from "benchmark") it's not as though I can say "well, I've made it this far, so I'm no longer at 55%, I'm at some higher number."

I'm thinking I'm looking at more like 60%.  That's not based on statistics.  That's based on my gut.  (Note: subsequent research will change this somewhat -- I'm reporting "real time" as it were from when I got this news).

Now, if I started treatment and somebody said "there's a 60% chance you will be cured" I'da been happy about it.

But I've gotten this far, and endured this much, and was anticipating a high number here...closer to 98% at this point than 60%.  The goalposts have moved.   Hawkeye Pierce was expected to leave Korea, and the mission county just went up on him.

I remember Hawkeye being more upset than this a lot of times but couldn't find a picture of him sobbing or screaming.  Trust me, I feel more frustrated than wistful.

So what does this mean?  What changes?

Nothing, really, other than I'll probably opt for continued Velcade even if it costs me my head of hair.

I'll fight.  I'll probably win.  I mean, what else am I gonna do at this point, give in to this sh*tty disease and die?

No, I will dig in and prevail.

But this sucks.

A preview of Part 2 to come early next week:  I've spoken with BB to get his thoughts on this and dug into some additional data about my own particular biology that augurs well.  It's not quite as bad an ending as the worst case from this blog entry.  It's still not 98%, though, which is where I started out last week.

Dammit.

Curetalk panel coming up on the 28th

Hello friends!

First, Alice Cooper never called me so I'm guessing those biopsies were negative.

Second, the Velcade is definitely causing the hair loss.  I stopped it for three weeks and the hair started thickening again and I felt better.  However, for reasons I will discuss in an upcoming blog, I'm going to keep with the Velcade, I think...lots to report on statistics and what not, not all of it great.

But, having said that, I'm still in complete remission as of my labs today -- everything looks good.

And so rather than kvetch, I wanted to let you know of my upcoming participation on another panel put together by my friends at Curetalk.  My other panelists and I will be answering questions about how we deal with therapy, side effects, and our condition.  I've seen some of the questions that have been submitted and it should be a very, very interesting discussion.

You need to register to participate and I think it's limited to 50 callers.  You can register at the link below, and a description of the panel follows.

I hope some of you can join us!

http://trialx.com/curetalk/panels/myeloma-cure-panel-talk-show-with-pat-killingsworth-on-28-february-6pm-est/.

Myeloma Cure Panel Talk Show on Thursday 28 February 2013 @ 6pm EST.

This February our Myeloma Cure Panel is going to be a complete patient oriented panel, an ‘ONLINE SUPPORT GROUP DISCUSSION’

A chance for patients, caregivers and their families to call-in and ask questions of our experienced patient panel including,

Not sure how to deal with all of the wondering and waiting?  When is it time to seek a second opinion?  What makes up an effective healthcare team?  How to cope with taking dexamethasone?  What can I do to help my peripheral neuropathy symptoms?

Cure Talk is proud to present an hour dedicated to answering your myeloma questions.  Please send in your myeloma questions to be answered by our experienced panelists on Cure Panel Talk Show - Pat Killingsworth, Nick van Dyk, Gary Petersen, and Sandy Hirsch

Welcome to my nightmare... (song title, not bad news)

Folks, it's been a little while since this blog has been amusing, so I thought I would post a minimal update here just because it struck me as funny.

In a post-Revlimid world, I have to be cautious about secondary malignancies.  Regular readers will recall I had to have my index finger carved up to remove a squamous carcinoma (skin tissue cancer).  Plus I had that nasty viral issue that manifested as hand / foot / mouth disease (not to be confused with hoof and mouth disease, which I might get one of these days).

The upshot is, I am pretty watchful as to my skin these days.

My wife noticed a freckle that seemed to be changing pigment, so I was finally, after some difficulty, able to get a dermatologist on my insurance plan who was recommended by my primary care physician.  I went to see her.  I won't even use initials here because what I'm going to say isn't the nicest thing in the world and I'm sure she's a very good doctor.

For starters, she was a dead ringer for Alice Cooper.

I mean this is almost an exact copy of her except Alice's eye makeup is a little less extreme than hers, and her hair was much more...uhh...vertical than this and quite a bit messier.

Now, I'm no prize myself most days so far be it from me to pick on somebody for their appearance, particularly when they're involved in my care.  But it was an amusing comparison.  I mean I feel like I'm looking at a picture from her medical school yearbook when I look at this photo here.

After giving her my illustrious medical history, including the skin cancer and the weird hand / foot / mouth thing, we went into an exam room.  The exam room smelled like...

Well, let's put it this way.  Ever know an extremely socially awkward, nerdy guy who was very booksmart in high school but whose parents never informed him about body odor?  When I was in business school in Boston, I took one class at MIT.  Every student there is, by some measure, a genius. But many, seemingly, fall into this category of brilliant kids unaware of basic anatomy when it comes to sweat glands and armpits.  I remember walking into a stairwell with about 100 of these kids and the concentrated BO was almost enough to make me black out.

The exam room smelled just like that.

Ugh.

I almost said something because I didn't want Dr. Cooper to think it was *me*, after all.  Then I though "my God, what if it's HER and I say something?"  So I kept my mouth shut.  She couldn't *possibly* think it was me, I thought to myself.  It smelled like an elephant had died in the place, had decomposed, and had only recently been removed.

I withstood a couple of biopsies of tissue on my back and will get the results in a week, after which I shall dutifully report them, dear reader.

The other thing I had Alice look at was my fingernails.  After falling out from the H / F / M virus, they have regrown fully (except for the mangled forefinger where only some of the nailbed is capable of growing tissue -- I'm growing that out as best I can so I have something there, but it ain't pretty).  There are some strange anomalies like a non-rounded nail on my left thumb (instead of just being one smooth arc from left to right across the face of the nail, it's ridged somewhat).  Dr. Cooper said this was nothing to worry about and was likely the result of the virus, which should resolve over time (months).

There you have it folks.  Next time you hear "Schools Out for Summer" or "No More Mr. Nice Guy," remind yourself to make an appointment with a dermatologist for a checkup.

Setting the record straight on my MRI

Okay...so this is one part public service announcement and one part making sure I've got my act together!

For some reason, I always want to think there are a "couple" of pits left in my spine.  I was looking through my last MRI, and there are five.  So in order for me to remember this important fact, I'm making a post on it.

The public service announcement is what I've learned about MRIs and how to read the report.  So I'm going to put mine up here and say what I think it means.  :)   The italics are my comments.

9/11/12

MR OF THE SPINE AND PELVIS  I got out of a full body one this time, saving me some time in the machine

MR TECHNIQUE: Sagittal T1 and STIR weighted studies of the entire spine and coronal T1 and STIR weighted studies of the pelvia.    Sagittal refers to the plane of the scan, as does coronal.  T1 and STIR are different types of scans.  My understanding is that the T1 has higher image quality, and STIR causes any lesions to stand out more prominently, so the two are used together.

COMPARISON STUDY: MRI of the spine and pelvis of 4/9/12  Obviously we're looking at how things change over time

FINDINGS:

STIR weighted studies of the spine and pelvis demonstrate a hypo to isointense marrow in relation to adjacent muscles.  On T1 weighted sequence, the marrow is hyperintense in relation to disc interspace.  Signal intensity is heterogenous on STIR weighted study and homogenous on T1-weighted studies.

Well this one is a mouthful.  There are three ways to describe the intensity of marrow relative to nearby muscles: hypointense (there is less of it), hyperintense (there is more of it) and isointense (it's the same signal strength as the muscles).  Because the T1 scan reacts more strongly to the presence of water in the body, it makes things look more hyperintense so the STIR study is the more important one to go by. According to this, I have hypo to isointense marrow, which means there ain't as much of it yet as a normal person would have, I think.  Probably not surprising since normal people haven't had their bone marrow totally destroyed twice by high dose chemotherapy, and then suppressed on a drug cocktail for three years.  :)

The other vector here is homogeneity (all the marrow is distributed the same) versus heterogeneity (it is more splotchy).  I'm homogenous on T1 but heterogenous on STIR; I'm not sure what that means although perhaps it means I'm not quite normal but getting there, in terms of distribution of the marrow.

In the cervical spine, heterogenous marrow is identified with no distinct focal lesion noted.  Degenerative disc changes at C5-6 and C6-7 is noted with disc protrusion as identified at C5-6 and C6-7 unchanged from the previous study.

These discs were on their way to being destroyed by the myeloma, but we got to them before they broke.  So they're a little tweaked but should be okay.  The marrow, again, is heterogenous -- MM attacks the spine in many cases and I was no exception -- it was active in a lot of places in the spine.  We'll eventually want the marrow to be homogenous here, I think.  C5-6 and C6-7 refer to the cervical vertebrae -- these are the 7 vertebrae beginning with C1 at the base of the skull and continuing down through the neck.

In the thoracic spine, small focal areas of hyperintensity involving the vertebral bodies of T2, T3 and T4 are again seen.  Fracture with vertebroplasty changes at T4 is again identified.  Vertebroplasty changes at T11 remain stable.  Focal areas of hyperintensity involving T10 and T12 are again identified.

These are the thoracic vertebrae and they run from the middle of the neck down through the back. Here, I have some patchy marrow (the hyperintense areas haven't recovered) and we see two of my repaired vertebrae and T4, and T11.  There are focal areas at T2, T3, T4, T10 and T12.  So five small spots that are still here.  They don't specify the size -- the time before they had been identified as 4mm or so.  

In the lumbar spine, no new focal lesions are identified.  Fractures of vertebroplasty changes at L3 and L4 are again seen.

The other two broken vertebrae are in my lumbar region, at the bottom of the back.  So that's a total of four repaired vertebrae.

In the pelvis, a slightly heterogenous marrow is noted without distinct focal lesions.  No evidence for avascular necrosis of the femoral heads are identified.

So again, the marrow is a little patchy here, but there are no remaining focal lesions.  This is good -- I had an 8cm lesion here at one point!  Avascular necrosis is bone death from a lack of blood flow that can be caused, it is believed, by chemotherapy.  So I'm glad they checked it, and I'm glad I don't have it!

IMPRESSION:

1.  Hypointense heterogenous bone marrow on STIR weighted studies.   I need more marrow, more evenly distributed, for this all to look normal.  How much is due to the Myeloma versus the treatment is unclear -- I suspect mostly the latter.

2.  Stable small focal lesions of T2, T3, T4, T10, T12 vertebral bodies.   This is the part I don't like.  Five of them, and they are stable -- meaning they didn't shrink from the last scan six months before.  This is what BB wants to go away.

3.  Stable vertebroplasty changes at T3 and T11 vertebral bodies.   They didn't sum up the lumbar ones...I wonder why?  I also wonder about the "fractures" reference -- is the vertebroplasty fracturing?  Or is this simply because those vertebrae had actually fractured before the vertebroplasty was done there, whereas in T3 and T11 they damage was caught before the bones actually broke.  Hmm....something to ask somebody about.

4.  No evidence for avascular necrosis of the femoral heads are identified.  Whoopee!!  :)


So there you have it, folks, the readout of an MRI.  And I have a reminder that I have FIVE lesions that I want to see fully resolve.

Thought on maintenance from a friend

Two posts in a week...been a while since there was that much newsworthy stuff to share!  :)

I'm pleased that among the many fellow travelers I've met on my journey is one terrific lady, CP.  I believe CP was diagnosed in 2011 and has been kind enough to tell me that she found this blog and her subsequent conversations with me useful in determining where and how to be treated.  She is being treated by Dr. GT, who worked with/for (depending on whom you ask, I suppose, haha) BB.

Like BB, GT believes the disease can be cured in a good portion of cases, though GT is more guarded about using that word, from what I can tell from the people I know that have seen him.  GT uses a similar program to BB.  Induction with VDT-PACE, two transplants, conslidation chemo (VDT-PACE again) and then maintenance.

A couple of interesting differences: during the second transplants, GT uses a different agent from Melphalan...I believe it's Bendamustine.  Another version of mustard gas, essentially.  I'm not sure if this is because he doesn't want as much Melphalan used, or if he wants to mix it up yet again.  Bendamustine is, I'm sure, part of the 9-drug cocktail SUPERBEAM that BB uses in "high risk" patients but he doesn't use it on low risk patients.

The other difference, which I learned from CP just yesterday, is that GT only does two years of maintenance.  And this is what I thought was notable enough to blog about.

The BB protocol is three years of VRD in maintenance (for those new to the blog or just reading this out of nowhere, I'm using a lot of acronyms in this entry -- please email me if you have questions.  In fact maybe I'll put a glossary entry up one of these days!).  After the three years, if all has gone well, you get a pat on the back, a hearty handshake*, you are told you're cured, and you go on about your business, with annual checkups to make sure everything is still good.

In my case, I had these stubborn pits in my spine, and at the time BB was very concerned (as was I) about the MYC gene that I had originally overexpressed in my baseline cytogenetics.  He took marrow from some former lesions and while we waited for the results, I contemplated the unusual position of having to undergo significant additional chemo (VDT-PACE, probably) despite being in complete remission.

Thankfully, the marrow came back negative and all looks good, including the MYC gene being normal.  And we settled on single agent Velcade as maintenance, because BB's theory (which he readily admits is just that: a theory) is that as long as those pits in the spine are there, some MM cells that haven't gotten with the program could be hiding under the proverbial rock, waiting to resume the party after the police leave.

So we stay on Velcade, as noted with some regularity.

At any rate, I had asked CP if she would ask GT for his thoughts on maintenance and she was able to do so, and he reported back a few things that are interesting both for their consistency and points of divergence with BB's protocol:

•  He doesn't believe in more than two years of maintenance, due to (1) diminishing returns, and (2) the likelihood of secondary malignancies.  It is worth noting that with respect to (1), the rest of my lesions other than the spine pits filled up with new bone during year two of maintenance, and the pits shrank during this time, and during the last year they have been stable.   With respect to (2), I'm typing this with nine fingers since my pointer finger had a chunk cut out of it from the squamous cell carcinoma I endured during the third year of maintenance, and this was also when pre-myelodysplastic cells (an early indicator of potential leukemia) showed up in my marrow.  So I would say that GT (whoops, almost typed his real name, although at this point I'm not sure why I bother with a thin veneer of anonymity) seems right on with regard to these points.  Sorry (and hello) to any UAMS folks reading this!

• He thinks that any lingering lesions are unlikely to have any MM in them.  

• He recommended doing a FNA (biopsy) of those pits, which is what BB wanted to do but they are too small or inaccessible to do that with.  So BB did the next best thing which is to needle several other spots that used to have active lesions.

• He said if they were still positive for MM, he would radiate them.  BB is not, to my knowledge, a big radiation guy.  And in any case I am negative for MM elsewhere, so hopefully these are negative as well.

The sum total of all this?  I'm sticking with the Velcade...but I might have gone to single agent Velcade a year ago and avoided getting my finger chopped up, and the scary pre-MDS cells...

All stuff for your consideration, fellow patients.





*n.b.,  Before editing the typo, I had originally typed "heart handshake."  Given the aggressive approach employed by BB and crew, I made sure to correct this lest people think that was an actual medical procedure!

Another reference to Myeloma being curable.

I'm involved in a number of online forums for the discussion of Myeloma (including some other blogs) and there is occasional a zesty debate about whether or not the disease is curable.

I have noticed, in the four plus years since my diagnosis, a growing number of doctors saying that the disease is being cured in some cases.  Of course BB's contention that the majority of newly-diagnosed cases can be cured is still an outlier, but it's increasingly less so (is that an oxymoron, or just poorly-written?) these days.

In one online exchange, a patient named Reed Whitener posted a reference to "his story" at the cancer center where he was treated.  Since his name is featured on the web page, I hope I can reproduce it here without offense.

At any rate, the website uses the "cure" word -- albeit in quotes.  Something to think about.  I've not hear of the Massey Cancer Center and I'm not even sure what their protocol is, although it looks like tandem transplants, which has been the centerpiece of BB's protocol for 20 years.

Here's "Reed's Story" at the VCU website. That's Virginia Commonwealth University, not Vet Care Unlimited! :)

More on Velcade allopecia

Hello folks.  I don't want to keep carping on this situation, particularly as I have consistently counseled people that hair loss in Myeloma treatment is a necessary evil that you shouldn't dwell on...but my primary therapy has been over for three years, damn it, and of all the crappy genetics that I've got, the one thing I've been fortunate enough to have is a good head of hair!

Anyhow, it's worth mentioning only because the guy who has been cutting my hair for the past ten years commented that the hair is definitely different than it was even two months ago -- more frail, brittle, etc.  There is definite thinning, and it's not happening in a normal "male pattern baldness" way.  It's happening on the crown or just behind it, but according to the hair dude I would have shown thinness there when I was 18-20 if it was going to happen, and since I didn't have that, this is not natural.  Hence, Velcade.

I will certainly deal with it and I'm not going to stop Velcade therapy just to keep the hair healthy, but I will not miss this drug any more than I miss Revlimid or Dex.

I document this mostly so those who search for "can Velcade cause hair loss" can find somebody to attest that yes, it can.

Onward and upward.  Hug your hair today.

Not much to report, other than ongoing Velcade inconvenience!

Happy New Year and good health to you all.

A brief update for you.

I was off Velcade for two weeks (meaning three weeks between infusions), though I did visit the doctor for bloodwork one week (the other week was Christmas).

I did get the stomach flu twice.  It had been going around, and I documented my first bout of it here.  The second bout came at the doctor's office, actually, on the day I was worried about extreme GI pain.  Turns out it was related to another bout...or at least I *think* it was given that I got sick in the parking lot after the appointment.  Eep.

The hair issue certainly feels Velcade-related as well.  It feels finer, dried out and more delicate when on Velcade than it was even with only two weeks off.  I notice it falls out when on Velcade as well.  The head itches, too.  I'm sure they are related.  It's not going to be enough to keep me off the drug as I want those damn pits in the spine to heal up.  But it's irksome.

The other GI ailments -- dysyntery, basically -- continue unabated.  They continued even while OFF Velcade, albeit not quite as badly.  So my poor intestines are going to need an undetermined amount of time off before I return to normal, even when off meds.

I confess to a bit of unease these days as I look around me and see friends who entered treatment around the time I did started to fail primary treatment and look for new methods of controlling their disease.  We're entering the phase where the "cured" start separating from the "controlled" and...well, I sure hope BB is right, is the point.  I have essentially reached the start of the plateau of the graph for low-risk patients that achieved compete remission.  In another three years I'm pretty sure I'm in the clear for good; in another two the life insurance vultures can start trying to sell me more product.

Meanwhile, it's watch, and wait, and hope I keep my hair!  :)

I do want to add that "chemo brain" is real.  I noticed a definite lack of focus and drive over the past 18 months.  I am still hoping to avoid Cymbalta (an anti-depressant), which BB has recommended from time to time.  However I'm starting to be more open-minded to it.  Still, I would rather get off all drugs for six months and see how I'm feeling before I decide I need something to keep the ol' serotonin in balance.

More to come as events merit...next visit to Arkansas in about 10 weeks.

A Velcade holiday?

Howdy folks.

Been an interesting and somewhat unpleasant couple of days here.

In order of severity:

Went to bed Sunday night with a lot of stomach pain.  I've gotten used to it conceptually, and although it's getting worse each week I figured I could ride it out until March when, hopefully, those stupid little pits in my spine have gotten with the program and I can stop meds.

I took a Vicodin, which usually dulls the pain enough to permit sleep.  It did, but I woke up yesterday morning with a terrible pain that I usually don't experience in the AMs.  I took one Vicodin and it did nothing.  I took another and it did nothing.  The pain was pretty terrible.  If I had one of those smiley face charts...




...I would have been Mr. Orange over there, second to the right.

I called GD's office, fearing that this could be C Diff or something awful like that.  Jill was concerned that it could be a "boomerang" effect from the acetaminophen (which is part of the Vicodin pill), as she had experienced something similar from migraine treatment years ago.  GD thought it wouldn't be this, and was unlikely to be C Diff, but could be something viral or bacterial.  He ordered some tests and we're going to wait it out and see.  I feel better this morning, although I still have a bit of a fever and some pain.  I was sick to my stomach yesterday but today the nausea has abated.

In other news, I think I am a rare case of Velcade-related allopecia (read: I'm losing my hair from this crap).  It's not a common side effect, but it does happen.  I've noticed some thinning and checked with the guy who has cut my hair for ten years and he said he'd not noticed anything.  So I'm watching that, as well.

Been a slow news day for a month or so...

Howdy folks.  I hope you and yours are off to an enjoyable start to the holidays.

Not that much to report, but a few things I should note for those playing the home game:

* I've been off Revlimid and Dex for almost 90 days now.  Tiredness is improving.  Mental acuity (which is one part related to tiredness or lack thereof, and one part independent of it) seems to be improving somewhat.  Face is not quite back to normal but probably 70% of the dex bloating is gone.  Heartburn gone.  What little neuropathy I had from time to time is gone.  Leg cramps gone.  Hurray!

* The Velcade dose, upped to 1.5mg/m2, is tougher to tolerate now than ever, in part because of the increased dosage, in part because the body is getting worn down from dealing with this weekly for almost four years now, and in part because the Dex used to mute the effects of the Velcade.  Sorry for the TMI squad here but in the interest of science I must report: the diarrhea remains unabated, although the frequency has dropped from 15X a day (yes, it really was this bad) to maybe half that.  The GI pain is more pronounced and intermittently affects me all week long, now -- I might have one or two pain free days before the next injection.  I use Vicodin to cut the pain; occasionally it is intense enough that I need to take two of them.  Not great, but I'm not taking more than six or seven pills in the course of a week so I don't think I'll develop a habit.  Nonetheless, I'm looking forward to not needing it!

* After being pretty healthy for a year (other than the hand/foot/mouth disease, that is!) I have had the stomach flu and now the regular flu in the last two weeks.  My white counts are no longer as suppressed as they were while on Revlimid, but we Brethren of the Weakened Immune System must remain ever-vigilant with our use of Purell lest we come down with something.  Tamiflu and Levaquin are holding the flu at bay but it's never pleasant.

* I recently had my blood tested for childhood innoculation antibodies, which SF at City of Hope had told me sometimes the body "remembers" after transplant.  Well, the body don't remember this stuff after two transplants...at least not in my case.   I have ZERO immunities...except to Chicken Pox since I had Shingles a couple of years ago.  I wonder if the presence of antibodies to Shingles means I can stop taking Acyclovir?  Something to consider...although I really don't want to do that until the killer cell (CD4?) count is back in normal range.  I do NOT want Shingles again.

Meanwhile, steady as she goes until my next visit to Arkansas in March.  I will nonetheless keep you posted in the interim!  As advance notice, BB will be on a Curetalk panel in February which I'm very much looking forward to joining.  And I'm sure there will be the occasional bit of news along the way.

Be well, all!

The Cure versus Control Discussion

As noted in a previous post, I participated in a panel hostel by CureTalk during which we discussed the issue of cure versus control in Myeloma treatment.  My fellow panelists (Jack Aiello, Gary Petersen and Pat Killingsworth) and I discussed a number of questions, including the following:

• Right now, there are two possible therapies that might “cure” select patients; donor transplants and Total Therapy. My question is this: From a patient’s perspective, are either of these intensive therapy options worth the small risk of a possible cure?

• What does “quality of life” mean to you? How poorly would you have to feel before deciding to stop a therapy that might significantly extend your life? and

• Specifically, if you were given the option of living five years relatively drug free, or six years using aggressive maintenance therapy all six years- complete with a long list of side effects – which would you chose and why?

It's worth noting that Jack, Gary and I all took issue with the phrasing of the last question -- because to us it's not a choice of five years with minimal treatment versus six years with extensive treatment.  We viewed it as five years versus ten or twenty.  And even then, the choice is not cut and dry.

You can listen to the 60 minute broadcast here.

http://www.blogtalkradio.com/curepanel/2012/10/29/myeloma-cure-panel-talk-show-with-pat-killingsworth

It's interesting to note that there seems to be a general feeling of the tide turning in terms of awareness that Total Therapy has the potential to cure many newly diagnosed patients.

Bad language but boy is this funny!

For those of you who may not be familiar with them, The Onion is a satirical website that mimics a newspaper or news-site.  The Onion originated 20+ years ago as a fake newspaper, started by (I think) students at the University of Wisconsin.

They've continued over the years, and for several years have been publishing a website.

I popped by there today and found a headline:  "Latest Study Finds Cancer Calls Now Cruelly Mocking Researchers."   Related articles include "98% of Babies Manic Depressive" and "Doctors Closing In On 'Second Head-Bonk' Amnesia Cure'".

Anyhow, the article in question is not only funny but also pretty well researched.  For example:

"The report confirmed that while all types of carcinomas are beginning to make researchers feel like garbage, myeloma cancer cells in particular think they're God's gift just because they're resistant to the frontline drug Velcade."

Bad language abounds, but for those not offended by such things, this is definitely chuckle-inducing.

http://www.theonion.com/articles/latest-study-finds-cancer-cells-now-cruelly-mockin,30074/

Myeloma Cure Panel Discussion: Cure versus Control

Hello folks.

On Monday, October 29th, I will be participating in my second panel discussion organized by Curetalk, an organization that hosts a number of dialogues related to cancer therapies.  I spoke on one of these a few weeks ago and was going to post about it here but my comments were overtaken by other events that I wanted to cover.

At any rate, I'm going to participate next week along with some other panelists including fellow Myeloma blogger Pat Killingsworth.   The tantalizingly controversial topic is, as noted above, cure versus control.

After we tackle that, we will address other questions such as "which is the one true God?" and "the definitive, simple solution to lasting peace in the Middle East."

The conference call, which is free to join, is limited to 50 callers, all of whom can ask questions of the panelists.  I urge those of you interested to register through the following link.

http://trialx.com/curetalk/panels/myeloma-cure-panel-29th-october-2012-7pm-est-on-cure-vs-control-co-host-pat-killingsworth/

For me, I'm very excited to participate in the discussion.  I will, however, be calling in from the airport in Las Vegas at the end of a much-needed mini-vacation.  I will try to find a quiet spot populated by people in the fetal position, listlessly searching their pockets for their once-full wallets.

In other news...Velcade Sub-Q has (thus far) the same side-effects as intravenous Velcade for me, with the added negative of painful bruising at the injection sites, reminiscent of Neupogen shots.  I am strongly considering switching back to IV Velcade -- they have to tap the port to check blood anyway...

Anybody have experience / thoughts on this?

Have a good week, everybody!

BD consult

Okay, on to more positive things.

After a couple of scheduling snafus, I was able to speak with BD, a long-time eader in MM research and therapy.  He was one of my original consults when I was diagnosed and I thought the current end-of-protocol-decision-point would be a good time to reconnect with him.  I was able to approach this with considerably less trepidation than would have been the case before getting the good news about my MYC gene a few weeks ago, so it was an almost philosophical conversation about when to end maintenance.

Highlights:

* I am doing very well.

* He observes that getting to four years of CR in the Total Therapy program is a meaningful achievement in terms of there being a flattening of the survival curve.  Readers will note I have mentioned this before.  I've got about ten more months.  For whatever reason, BB would have been okay taking me off therapy at three years of CR if those pits were gone, but as they're not, we continue.

* He suggested that Zometa will not cause those pits to heal up -- Zometa stops osteoclasts from destroying bones, but it doesn't accelerate healing.  So that means no more bisphosphonates needed.

* He believes, unlike KA, that I shouldn't be on proteasome inhibitors forever -- even if they become a simple oral alternative.  Rather, I need to get off all this stuff to allow the body to heal.  He noted the squamous cell carcinoma in the finger is an example of my body having been pushed to its limits by the therapy and I don't disagree.

* Having said that, he believes single-agent Velcade is not a bad idea until the pits clear up, which could take quite some time.

* He thought Interferon wouldn't do anything, though as I pointed out BB's musings about this were before we saw the normalized expression of the MYC gene.

* He thought radiation of the four pits could be a possibility in the event there are any rogue cells in there...but he also thought that without any evidence of the disease, it wouldn't be worth it, and he further noted that radiation impedes the healing process.

All in all, his hope would be that I could get off Velcade in the next 3-6 months, pending the results of MRI/PET that would show the pits are gone completely.  As I'm going back to UAMS in March, that is a logical time to stop the Velcade if I'm able to do so -- but I want to wait until those pits are straightened out first.

On the strength of this and the normalized MYC, I'm feeling like I may not need my third "second opinion", which was to come from MAYO Scottsdale and a doctor there who specializes in MYC.  That's scheduled for this Thursday but it can only be done in-person and for anybody that knows my job, it's a real pain to get time off to do anything.  They give me time to go to Arkansas twice a year now and I appreciate that much -- taking off more time seems like it may not be critical.

I shall have to think about it!

Quick post on the Beacon drama

No good deed, it has been said, goes unpunished.

And how.

A doctor from another institution recently published an article calling into question the mortality statistics from UAMS.  Essentially this article didn't dispute the percent of patients who were still alive at a given point in time (UAMS' strong suit) but it disputed the percent of patients whose cause of death was reported as "unknown/undetermined" instead of treatment-related.  He accused UAMS, essentially, of downplaying the percent of patients that die from the toxicity of the program.

UAMS is defending itself, though frankly not as aggressively as I'd like.  It's uncommon, I believe, for doctors to wage public war over stuff like this but this episode has certainly given those opposed to BB for whatever reason an excuse to vent their spleens.

I went to the Myeloma Beacon website after have been warned of some of this by BJ -- and I feel I owe a little something to BB and the team since they've saved my life.

I ended up stepping into a snake pit over there.  I've already over-participated in the thread so I won't be posting anything further there but I have an observation and a request.

Observation: the fact that people with a life-threatening disease don't have better things to do than denigrating both those working against the disease and those patients who choose a different treatment plan than their own would be mind-boggling were it not so depressing.

Request: For any of you who read this blog and are "offended" when I point out that BB used particular protocols before they were generally accepted...do us both a favor and stop reading this blog.  It wasn't meant for you and we'll both be happier.

BB's phone message, KA's advice and sub-Q velcade

Some quick and sundry updates here.

First, although I had pried the information from his team last Friday, BB himself called me on Monday (I don't know why but I didn't see the phone "ringing" or vibrating).   I was hoping to actually embed the audio here but I can't do it at this time (will do my best since the cadence is what makes this humorous).   Anyhow, the voicemail is:

"Hey Nick, this is Bart.  All studies are good and negative.  Okay?  Great news.  Calm down.  Thanks, bye."

I feel like saying, in full Walter Sobchek mode, "I'm perfectly calm, dude...calmer than you are."   And I am, in fact, pretty calm these days.

So the plan at present is to continue on single agent Velcade in a ~20% higher dose (1.5mg/m2) until those damn pits in my spine heal up, with a check-up (including bone marrow, PET, MRI, etc.) in six months' time and cancer markers run every two weeks from blood.

I spoke with KA yesterday on a phone consult to validate this approach.  It was a very pleasant conversation, the highlights of which were:

• He agrees that I should remain on something to ensure the full adherence to BB's approach with its hope for cure

• He agrees that Revlimid should be discontinued since I've had a ton of alkalyting agents (e.g., platinum, adriamycin, cytoxan, etoposide, melphalan in high dose) that alter DNA and it is in combination with these alkalyting agents that Revlimid use is most likely to lead to myelodysplasia and, potentially, Leukemia

• He thinks Interferon wouldn't do anything other than make me feel like I have the flu constantly

• He thinks a proteasome inhibitor (like Velcade) could be a long-term option for me (as in potentially forever) and that in a couple of years there is likely to be an oral version (i.e., a pill) that would make it easier to take.  I think he doesn't full subscribe to Bart's confidence in a cure provided the MRI is clean.  We'll see -- this stuff remains poison and I don't want to be on it forever.

• He "wouldn't sell the house simply because of the MYC gene."  While it is no longer over-expressed, I still wanted KA's thoughts on it.  He said that "with respect, [BB] is probably guessing about its responsibility for the remission loss" and I'm sure BB might agree, but I don't know how extensive the regression studies are so it might be a very educated guess -- or it could be statistically proven.  At any rate, the fact that it is normally expressed gives me some comfort -- particularly when combined with BB's voicemail.  I asked KA what maintenance drugs target MYC and he said "a few years ago, I'd have said none...but it turns out they all do.  Revlimid is particularly effective."  So perhaps Revlimid is what caused the MYC to normalize over the last three years of therapy.

• He noted that over time, the bones should resolve and the heterogenous marrow should probably even become homogenous but that he wouldn't use the latter as a requirement of remission (he wouldn't say cure, obviously).  He said that PET scans were extremely sensitive and the marrow funkiness could be caused by many things (e.g., an inflammation).  I didn't bother to mince words and point out that we were talking MRI since clearly Arkansas and Dana Farber diverge on treatment long before this point.

I thought it was good that one of the world's foremost experts on novel drugs (versus transplants) essentially concurred with BB at this point.  I'm going to continue with a couple more opinions because one other common point of commentary between BB and KA was that "we're in uncharted water here" insofar as there are no studies to point to.  So it can't hurt to get a couple more viewpoints to corroborate the approach.  Next up is BD.

PHEW!!!!!! Good news from Arkansas!

First of all, thank you all SO much for your prayers, emails, voicemails, texts, comments, intentions, positive vibes and well wishes.  They do make a difference, both in how challenging news is handled and, perhaps, in the outcome of events.   I deeply appreciate them!

So, let me share the good news.  My gene array came back about as good as it possibly could have, which means:

1.  Negative for myeloma (and this was in the heterogenous marrow of a former lesion, so if it was gonna show up anyplace, that is where it would show up)

2.  "No cytogenetic evidence of myelodysplasia" which means, most likely, that there were some funky looking white cells but they are made to look funky by the Revlimid, rather than my body manufacturing them.  We're off Revlimid so hopefully that will all resolve by next time but meanwhile, my marrow doesn't appear to be pre-leukemic.  Phew!!!

3.  The MYC gene which was over-expressed (the numbers being 18,390 and 13,928 in the two gene arrays I did before I started treatment, 17,000 after one day of Velcade and 19,602 after one week of treatment) came back at 3,200.  This puts it clearly in the second quartile (meaning somewhere between 50 and 75% of patients have more of this gene than me).  I need to speak with Bart to find out what this means, exactly, but it's no longer over-expressed.  So that MAY mean that I don't need to worry about spontaneous remission loss.

Triple phew!

One lingering question I have is whether or not my friend BB (the patient, not the doctor) who unfortunately lost remission due to this MYC gene had experienced a similar "normalization" through therapy -- in which case I'm not out of the woods -- or if his MYC gene had never been "normalized."  If the latter is the case, than it likely means that I won't face a high chance of remission loss -- and it means that BB (the patient) can look to his own MYC marker going forward in treatment as something that could indicate the efficacy of his therapy.   If the former is the case, then I still need to worry -- because he lost remission and if his MYC gene was normalized, then even though mine is not being over-expressed, I'm still at risk.

At least until those lesions resolve and the bone marrow becomes homogenous.  I had thought we only needed to look for the first but based on BB's (the doctor, now) concerns last week I might need to wait for the heterogenous marrow to give way to homogenous marrow.  Although I'd also been told in the past that this may never happen given the destruction of the marrow during transplants.  So I'm not sure.

Another conversation with BB (the doctor) is in order and I'm setting that up.

We still need to figure out what maintenance drugs to use since I'm now off Revlimid -- we want those stupid pits in my spine to heal up so we can breathe easier and get back to the "you're cured" track!   How I long for those words...

For the moment, though, the concerns of last week have abated.  Good lord, it's hard to explain how much stress that puts somebody through -- I'm not sure I fully realized it myself until the burden of that anxiety was lifted with this news.  I'm really emotionally spent.

Time to celebrate this evening with a great bottle of champagne!!!

Thank you all -- I will continue to update frequently as I learn more, including in numerous consults over the next couple of weeks.

The second opinion derby, redux

Howdy folks.

After getting knocked about a bit, I think I have found my sea-legs a bit and am going about the process of speaking to people that have specifically studied this MYC gene and may have thoughts on how to target it with specific maintenance drugs.  Of course my hope and expectation is to still handle all of this through UAMS but it can't hurt to be informed and I feel like BB is operating from the gut versus from a pool of data so it also can't hurt for me to understand how other's guts would lead them.

It may be challenging to do so.  Consider the fact, for example, that I remain in complete remission.  I can't send anybody slides of bone marrow because it won't show any myeloma cells.  I can't send anybody blood because it will be normal.  Nobody else really uses MRIs the way UAMS does; if I sent them an MRI it would show a few small inactive lesions and some heterogenous marrow which is to be expected from myeloablative therapy.

I think there are probably a limited number of doctors who would even consider ANY kind of maintenance for somebody in my condition, having concluded three years of VRD and retained remission that whole time.

Nonetheless, I've begun looking at which doctors have looked at the MYC gene -- either with respect to Myeloma or even with respect to other blood cancers.  The people whom I'm hoping to speak with include:

- KA at Dana Farber.  He's done work on MYC and he's a leader with novel agents.  Ironically, friend and fellow blogger GP was incredibly kind and sent a brief summary of my situation to KA's partner, PR.  He responded immediately by saying I should be speaking to somebody else outside Dana Farber. : \   Oh well, I'm still intending to do my phone consult with KA next Tuesday.   But this leads us to...

- RF at Mayo Scottsdale.  He evidently has done extensive research on MYC and is considered the leading expert on this gene (or at least one of them).  He's done presentations with BB on treatment of high risk MM before so they at least know each other.  I've sent an email to him asking to set up a consult, but haven't heard anything as yet.

- BD at Cedars Sinai.  A luminary researcher, he's done work on MYC and probably understands this disease as well as just about anybody.  I have a call into him to schedule a phone consult, although I could also drop by since he's local.

- SF at City of Hope.  He's got a tremendous amount of experience across different types of blood cancers and has done work on MYC.  He also understands BB's protcol.  And he's a great person.  And close to home.  So that checks a lot of boxes.

We'll see if I can speak with at least two of these people -- I'm particularly keen on speaking with RF.  Then we'll have some idea of what to throw into the mix along with Velcade if the gene array indicates that I still have this MYC gene running amok.

If I don't, then this is all much ado about no--  well, much ado about very little.  I'll still need to stay on Velcade until the lesions resolve even if I don't have the gene problems.   But that will be a bump in the road versus a majorly disconcert event.

Fingers crossed for good results on Friday.  BJ sent me a little text, since we had trouble getting cells from one of the bone marrow sites, that the results are "going to be good...or it wouldn't be this hard" (to collect the cels, I hope).   I presume that at least means that if I had myeloma cells the marrow would be more substantive.  This is part of what we hope for, but really we want:

* No myeloma cells
* No myelodysplasia
* No over-expression of MYC

If we're good on all those fronts, then we return to our maintenance program with Velcade alone, most likely, and watch and wait for those little spine pits to resolve.

I shall keep you posted.

I must also say I am particularly touched, as always, by the emails, calls, texts and posts offering support, prayers, positive thoughts and intentions, and even humorous and insightful historical commentary on the evolution of certain conventions in grammar!  :)

A more thoughtful recap of my current status

Hello friends.

I've had a couple of days to think through what the current situation is and so I'm going to try to recap it here.

I've finished three years of maintenance therapy.  This is supposed to be the "woo-hoo!" moment at UAMS when BB tells me "the Myeloma is gone and will not be coming back" and I can drop all meds except Acyclovir (the anti-viral that keeps Shingles away, which I need to stay on while my immune system recovers, which it would finally be allowed to do since I would be off the meds that suppress it).

Quoting the now 70+ year old BB directly from last week's appointment, "my usual approach is to continue to treat until such time as all the sh*t is outta there, so to speak."   This means traditional evidence of complete remission (no M-spike under the most stringent blood tests, normal urine, normal marrow) but also what BB called "Arkansas complete remission" (or MRI complete remission) which also means that all formerly-active lesions in the bones are fully resolved (i.e. replaced / refilled) with new bone, as confirmed under MRI.  His hypothesis is that these lesions are microenvironments in which myeloma cells can restart.  If the lesions are replaced with bone, it means they won't be able to do so.

We have been watching my 19 formerly active lesions resolve over the last three years of maintenance therapy, and all have gone (so I thought) except for five small ones in my spine, which have shrunk from 2.5cm at baseline (i.e., when I showed up to be treated) to 4 mm as of a 18 months ago.  But they have remained stable over these past 18 months.  I was hoping to see them gone since in addition to the normal maintenance protocol of Velcade, Revlimid and Dex, I was on the bone-strengthening bisphosphonate agent Zometa, the frequency of which was increased to one infusion per month over the last six months (I think I got four of them, actually -- same difference since this aspect of treatment is far from an exact science).

Last week, the MRI revealed that the five spinal lesions had still not resolved.  They were termed "small" and were not sized, but in the summary of results they were considered "stable" relative to the last scan six months ago.  This was problem number one.  BB wants to continue to treat until such time as...uh...well until such time as these are fully resolved, to use more polite phraseology than was employed in the actual consult.  In and of itself, this wouldn't be a huge deal...but this prompts questions about what medicine(s) to continue to take while waiting for resolution, and how effective they will be.

I've been on Velcade, Revlimid and Dexamethasone for three years of maintenance, but readers will know that I've had concerns about continuing on Revlimid.  It has been a key agent in maintenance therapy since Total Therapy 3 was begun in around 2003 and is widely used now.  About a year ago, it was noticed (by numerous entities, including the company that produces it) that Revlimid was associated with secondary malignancies -- solid cell tumors and leukemia, to be precise.  I had a squamous cell carcinoma in my finger, so we can check that box.  I had pre-leukemic cells in my marrow six months ago...so before we check that box, BB wants me off this stuff.  I agree.  For a while, the value of Revlimid (inclusive of these risks) is a no-brainer.  But after three years, has it done everything that it should do?  Is it now at the point where the risk of continued use is greater than the risk of remission loss?  Perhaps.  In fact, normally I would be pretty easy to convince except for certain aspects of my current situation.

Then there is the matter of -- for someone looking to continue maintenance with some urgency -- what it can be replaced by.  I want to keep up the attack on whatever rogue cells aren't yet with the program and make my body as inhospitable as possible for Myeloma cells while my bones continue to heal.  I suggested Pomalidomide, which as many readers know, is the next generation Revlimid.  BB said "yeah, good idea, but we can't get it."  I believe this is because Pomalidomide is still only available -- even to Arkansas -- as a single agent except perhaps in refractory cases, and I'm thankfully not yet a refractory case.  And if we are to use just one agent, BB wants to keep me on Velcade since he believes this is the most effective anti-Myeloma agent there is.  He asked me if I can tolerate it without the Dex and I said "sure!" -- mostly because I want off the Dex.  So that does seem to indicate that Dex in maintenance is not used for its plasmacytolitic (i.e. killing plasma cells) properties but because it helps counterract the effects of Velcade (flu-like symptoms, GI issues, etc.)    I will be increasing the dosage of Velcade from the already high 1.3mg/m2 to 1.5mg/m2 (normal is 1mg, and that's for people with raging disease, not the complete remission which I currently enjoy).   And Velcade has caused a lot of GI pain that requires Vicodin to keep at bay...so I'm not looking forward to increasing it.  However, Dex is responsible for a lot of ills so I'll be glad to be rid of it.

So all this would be fine, if a little unnerving...I'm done with maintenance, I'm still in complete remission, I've got some small lesions that haven't resolved yet, and I'm staying on Velcade until they fully resolve.

Except it's not that easy.

UAMS is very advanced in its genetic assessment of the disease.  In an era where most centers still rely on something called FISH (fluorescence in situ hybridization), a test that was developed 25+ years ago to look for out-of-place chromosomes, UAMS uses an assessment of 80 genes which, given its massive database of tissue samples, can indicate the risk profile of a given patient with accuracy.  The test is called a "gene array" or "gene expression profile" and involves a large core sample of bone marrow.  I had four of these done over about a four week period beginning a little before my therapy started in February of 2009 and going a couple of weeks into it.  These tests indicated that I had low-risk disease with some high-risk characteristics, and based on those high-risk characteristics I was given the additional Velcade (1.3mg/m2 versus 1.0mg/m2) in maintenance.  I have not had a gene array done since then because (a) they are painful, and (b) they did not have further clinical significance other than assigning this low- or high-risk categorization.

Until now.  Now they are still painful, but they do have some further clinical significance.

One of the genes they profile is called MYC.  This gene was originally linked to a type of Lymphoma.  Is essentially acts as a "utility infielder" with respect to genetic screwups that cause cancer.  Myeloma cells are abnormal either because chromosomes have been deleted (chromosome 13 is a common deletion that used to be considered a high risk factor, as an example) or added, or because there are chromosomes that have been translocated within a given cell (meaning parts of the cell's genetic code have been swapped).  A common if not typical translocation is 4;14 -- meaning the 4th something-or-other is where the 14th-something-or-other should be and vice versa.  And the commonality of some types of translocations means that there are certain genetic components that are prone to swapping with other parts.

The MYC gene acts as a utility infielder because it can essentially cause any part of the genetic locus on which it appears to swap with any other part.  Having this gene over-expressed is therefore a bad thing.  In the not-quite-four years since I started therapy, they have learned enough to know that it is, in fact, a VERY bad thing.   When I was originally diagnosed and BB was going through the genes with the chief genetic dude in his group, they were puzzled by something.  I had some important low-risk factors, but a puzzling backdrop.  They didn't understand its significance at the time.  Now they do.

This MYC gene, along with the others, is measured in some kind of units.  I don't know the scale, but it looks like, from a review of my data, everything is in the 300 to 1500 unit range.

My MYC genes were between 13,000 and 20,000.

And the significance is this MYC gene can cause a sudden and unexpected loss of remission in low-risk patients that have done well in therapy and are seemingly on their way to being cured.

To wit, me.

And my friend BB (a patient, not the doctor), who unfortunately lost remission about six months ago and has been undergoing absolutely hellish treatment trying to get the disease back under control.  He has been told by BB (this time the doctor), who originally told him he was likely to be able to cure him, that "we are not talking about cure any more...we are talking about control."  And BB (both of them) know the prognosis is dire.  Essentially BB (both of them, but especially the patient) is relying on new agents to be developed so that as current ones fail -- including both Carfilzomib and Pomalidomide in BB's case -- new ones can take their place and keep the Myeloma at bay.

Since my MYC gene is "sky high" to quote BB (back to the doctor now, unless otherwise noted) I am at particular risk for losing remission, and to be frank, losing my battle here.

In short, if the disease comes back, I move from the green line to the blue line.   The Y-axis is remission but might as well be a proxy for survival.

You will see that the green line (hell, I think it's green, I'm colorblind and on a graph of this size I can't distinguish it well...it could also be red, but I know it's not the blue one) is almost flat after three years.   Let's say that 95% of people don't lose remission, among those 148.   But it might be that 10 of those 148 have this MYC gene and 7 of them lose remission.

Unfortunately, that is the sub group in which I may now find myself...

UNLESS the three years of therapy I underwent have caused my genetic profile to change and this MYC is no longer expressed abnormally.

So I underwent several Fine Needle Aspirations of former lesion sites to see what the genetic material in there looks like, and a gene array, and a regular bone marrow.  I will be looking for the results of the marrow (to confirm continued remission and hopefully not to reflect any pre-leukemic cells) in the next couple of days.  It should have been done last week but the sample was damaged somehow -- this has no clinical significance.   They may just have dropped it or it may have been done in a former site where there wasn't enough marrow left to do anything with.   So they are going to use one of the FNA aspirations for this analysis instead.

I will be looking for the result of the FNA to additionally confirm that there are no myelomic cells.  The pits in my spine are not large enough to take a sample from, but they can go to a former site in my hip (which is where they went) for it, so they took a number of samples there.

This brings up ANOTHER problem.  I was told the lesion in my hip (the ilium, for you bone fans) was fully resolved.  But evidently BB and RVH (the guy who does the FNA work and reads MRIs) aren't fully satisfied because there is heterogenous marrow there.  So I may not even be able to be as confident about the lesions I *THOUGHT* were resolved...let alone about the ones that haven't resolved yet.

Anyhow, if the marrow and FNAs are normal, then I will be waiting only on the gene array analysis which will not be ready until Friday.  This will be an important one because it will reveal how extensively the MYC gene is expressed.

If everything is normal, then I breathe easier, stay on Velcade and wait for the lesions in the spine to heal.

If the current marrow is normal but the gene is still expressed, then I have to consider more aggressive therapy -- even though I am still in complete remission.  And I will be scared to death.

If the current marrow is abnormal, then it's even worse.

All this makes the selection of the ongoing drugs that much more important.  If I'm only on Velcade, will that be enough?  After I suggested Pomalidomide, BB said "I'm also thinking possibly Interferon" which was a component of earlier Total Therapy trials but which wasn't demonstrated to have any increase in overall survival -- just progression-free survival.  So it was removed from the protocol in favor of VRD maintenance some time ago...I don't know precisely when but it's out there on the interwebs (sic) for anybody who is really interested.   This makes me nervous...BB normally has an answer for everything and now he is operating on intuition and gut instead of data and protocol, and that scares the crap outta me.

I then said "do I need to do something more drastic, like another round of VTD-PACE."  Long-term readers, as well as other informed Myeloma folks, may recognize this as a cocktail of potent chemotherapy including Cisplatin, Adriamycin, Cytoxin and Etoposide, as well as the comparatively trivial velcade, thalidomide and dex.  BB smiled wryly and said "this was going through my mind as well...this is the problem with you, you know too damn much."  :)    He then suggested that I consider going on anti-depressants as he wanted to be completely honest with me about what he is giving me and why, and that the conversations were likely to lead to a lot of anxiety.  I certainly understand the anxiety part...and I have NOTHING WHATSOEVER against anti-depressants or those who take them.  However, I'd resisted them in the past because I knew I was going to be putting chemicals into every other organ in the body and taxing the heart (Adriamycin), the ears (Cisplatin), the liver (EVERYTHING), the kidneys (likewise, everything), etc.  I wanted to keep the brain as one organ that wasn't targeted for chemical change.  I have also "lost a bit off my fastball" in terms of mental acuity, which is VRD-related and should improve as these meds are reduced or wound down...but I don't want to do anything else to the ol' bean if possible.

Nonetheless, I can't deny that facing the renewed prospect of the sleeping dragon here -- after I thought we'd been going about the process of slaying it rather effectively over the past 3.5 years of aggressive therapy -- is a very disconcerting and stressful thing.  Depending upon the outcome of these marrow tests, I may or may not need to add Cymbalta to the drug cocktail that I will be on.  In the meantime, I shall medicate with mild doses of fermented juniper, grapes and wheat as circumstances merit (usually determined by time of day!)

So my friends, triumph is momentarily replaced by trepidation.  Confidence by anxiety.  Relief by stress.

What remains constant are the love and support of my family, my friends, the readers of this blog, and the team at UAMS -- for all of which I am grateful.

(Addendum: apropos of my recent Churchill reference, he is reputed to have said "ending a sentence in a preposition is something up with which I shall not put."   How does one properly conjugate the preceding paragraph?  I could see "for which I am grateful" except I really want to convey the point that I'm grateful for all the components of support!  Got any suggestions?   This is the type of crap that I think about to keep my mind off my physiology at 5:13AM!)