Thursday, November 28, 2013

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.  : )

Tuesday, November 26, 2013

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!

Tuesday, November 19, 2013

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.

Monday, November 18, 2013

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!

Thursday, November 14, 2013

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.  :)

Thursday, November 7, 2013

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...