Monday, September 17, 2012

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 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 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 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!)


  1. Nick -- Again, prayers for the best outcome possible on Friday. You are amazing at keeping us up todate and teaching us new things about the disease-- all while sweating this out. Truly an inspiration. Thank you, Linda (in Chicago)

  2. Hi Nick - UAMS is fabulous and has contributed immensely to the therapy of Multiple Myeloma. It would not be disrespectful to get a second opinion concerning c-Myc from Dana Farber. They are doing amazing research there. Nona

  3. Linda, thank you. Nona, that is an excellent idea and I had been thinking along those lines, both with respect to Dana Farber and with respect to perhaps Tricot because he has a similar approach to UAMS (having worked there). I spoke with Ken Anderson at DF before beginning therapy so I might try to revisit things with him.


  4. Nick, Prayers from The Netherlands for you !!

    Pieter From Holland.

  5. Nick, a second opinion is an easy process at Dana Farber, and it is not that expensive. I wrote a post on my blog about it and you can see it at the following link:

    Good Luck and God Bless/Gary

  6. We love and care for all of you so much. Lean on those you love and those who love you to lift you up. Keep fighting the good fight. We're here for you always. XOXO, Julie

  7. Wow, Nick, I really didn't understand most of what you posted. It sounds really scary. I would be really freaked. But it sounds like you are in excellent care and a plan is in place. Keep us posted. If you need the antidepressants take them, for me when I have extreme anxiety, Ativan relieves it . But I don't know if I had to face this if Ativan would be enough. Best wishes to you I hope the next tests results are positive.

  8. Nick, that is a lot to process. We are definitely pulling for you and will be praying for you and Jill this week. May all the news you receive be positive, and may you be surrounded with lots of peace in the mean time.

  9. Keep up the good fight, Nick. We've never met, but I've been a fan of the band for a few years now. I'll spin "This Mortal Coil" once again and say a prayer for you and your family...

  10. Nick - just wanted to let you know that I am thinking about you as you traverse these latest mountains. Your extremely well written and comprehensive post gives me great pause for thought as I will soon be ending my UAMS TT4 maintenance, if circumstances allow. Count on my deep and continued prayer for you, Jill and your family. My family has been praying for yours since we met in the stem cell floor in 2009. Sean

  11. That's an incredibly thoughtful and astute post Nick. I learned a lot. No advice on conjugating that last paragraph - it flowed smoothly when my eyes went past it.

    I hope that the Friday results will put you a bit more at ease.

  12. Nick,

    Thanks for the deep caring in your beautiful post. I know you will do your very best-- and things may not be as adverse as 4 AM suggests. I do have the sense that you will come out on top. Just getting off Revlimid and Dex will have you feeling better soon-- regardless of the juniper berries.

    Should it reach that point, I would second the suggestion of Dana Farber as they were working on several therapies that show good promise.

    I meet Pat Killingsworth later this week at his support group; we'll both toast you with a beverage and good wishes.


  13. I have followed your blog now for quite some time. I have read every entry that you have posted and have been encouraged by many of the things that you have written. The only thing that has bothered me is UAMS claim of a "cure". When I was diagnosed, three of my doctors, a hematologist/oncologist, a neuro-surgeon, and my GP, all said myeloma is incurable, but it is treatable. I trust them all. I have also gone by the vernacular that there is no complete remission, rather a complete response. Every myeloma patient is different. My doc has had some patients live fifteen years beyond diagnosis and others only a few. I'm hoping for the fifteen range, but you never know. Nick, I know you think BB walks on water, but I've always had this suspicion that he has been making promises to people that won't always pan out.

  14. Nick, we are hanging on your every post and sending encouraging thoughts and prayers your way. If anyone can beat this thing, it's you. Keep the updates coming - we will be looking for them.

  15. As a possibly amusing distraction, I'd like to point out that the whole "don't end a sentence in a preposition" rule was singlehandedly foisted upon us by Restoration poet John Dryden, who personally hated the construction. Moreover, he pronounced it in the 17th century equivalent of a rap diss directed at Ben Jonson, whom he held to be whack. Let this trivial bullshit be a comfort as you medicate from the cellar!

  16. Continuing to intend that you are getting good news, good advice and good medications, whether from your cellar or elsewhere... for the highest and best good of all concerned, so be it and so it is!

    I have to say that although I have followed your blog from the start, this is one of the most detailed and informative works you have posted. I continue to be impressed with your diligence and details, knowing you are sharing so others can have knowledge, too. Hats off to you!

  17. I don't even know where to start, Nick. You shouldn't be worrying. Instead, enjoy your remission! Cured, not cured... You are OK TODAY! One note: What, Barlogie's patients are immune from myeloma developing drug resistance? Really? Get off the stuff! That way it will be available if you relapse. (Note I said "if," not when like I would write on my site for all the rest of us...