Followup to Last Post

OK, I didn't come back last night to expand on my previous post.  I was sorely tempted to, since I lay awake in bed until after 3:30 this morning, but I took pity on you.  

You might say, 'Why don't you take a sleeping pill?".  Well, I'm a bit loath to add yet another pill to the impressive array I already take every day, enough to choke a good-sized horse.  The sleeplessness usually only lasts one night, so I can live with it.  Actually, I should get outside with a flashlight and work on some of those house projects.

It's a good thing I'm on a protocol that calls for low-dose dex (40 mg, once a week).  Prior treatment regimens used to call for high-dose dex.  I really feel sorry for those poor blokes.  If I were on high-dose dex, I would have been out in the treetops in our yard last night, swinging from branch to branch. 

While we were at the recent Patient Symposium, one of the doctors mentioned a patient requesting to get off the dexamethasone.  Another of the panelists jokingly questioned whether it was the patient or the family members making the request.

I promised to explain the MM response criteria in my last post, so here it is if you can decipher it:

International Myeloma Working Group uniform response criteria                       

Category                                                                           Criteria ______________________________________________________________________

Stringent complete response       (sCR)	CR as defined below PLUS: Normal SFLC ratio, AND Absence of clonal plasma cells in marrow by immunohistochemistry or flow cytometry _____________________________________
Complete response (CR)	Negative immunofixation on the serum and urine, AND Disappearance of any soft tissue plasmacytomas, AND ≤ 5% plasma cells in bone marrow ______________________________________
Very good partial response (VGPR)	Serum and urine M-protein detectable by immunofixation but not on electrophoresis, OR ≥ 90% reduction in serum M-protein plus reduction in 24h urinary M-protein by > 90% or to < 100 mg/24h _________________________________________
Partial response (PR)	≥ 50% reduction of serum M-protein, AND reduction in 24h urinary M-protein by ≥ 90% or to < 200 mg/24h, AND ≥ 50% reduction in the size of any plasmacytomas present at baseline _________________________________________
Stable disease (SD)	Not meeting criteria for CR, VGPR, PR or progressive disease __________________________________________
Progressive disease (PD)	At least ONE of the following: > 25% increase in serum M-protein in 3 months (absolute increase must be > 5 g/L), OR > 25% increase in urine M-protein in 3 months (absolute increase must be > 200 mg/24h),  OR > 25% increase in bone marrow plasma cell percentage (absolute percentage must be > 10%), OR Development of new bone lesions or soft tissue plasmacytoma, OR Development of hypercalcaemia

Day 1 of Cycle 3

Today was the first day of my 3rd cycle and the chance for us to meet again with the medical team.  It started with the blood draw, where they sucked 13 vials out of me.  Yikes!

After that, I renewed my Revlimid prescription.  I expected my copay to skyrocket today, since I thought the Good Days supplemental payments were going to run out, but they still only charged me $20.  It feels kind of like when the IRS sends you an unexpected refund.  It seems almost too good to be true, and in the end, it usually is.  So I'm waiting for the other shoe to drop on this, but in the meantime, I'll take it.

I had a bunch of questions for today, and I got most of them answered.  I was curious about the status of the MLN 9708 clinical trial (No. TX93639).  I was the last patient to be enrolled in Phase I of the trial.  It is now on hold waiting for administrative approval to move into Phase II.  Interestingly, they have decided on a different standard dose of MLN 9708 for new Phase II patients.  Instead of  calculating the dose based on Body Surface Area (see my Sept. 4 post), they will give all new Phase II patients a fixed dose of 4 mg.  I am taking 5.8 mg, and it is planned for me to continue at this dose as long as I am in the trial.  I don't know why they decided to modify the dose going forward, but as long as I have no side effects, I'm glad to be getting the higher dose.

I already know that two of the three prior DFCI patients on this trial have achieved a complete response to the medications, I was curious about how patients at the other participating facilities have been doing.  I didn't get a full answer on this, but apparently the DFCI patients are doing the best so far.  I'm still curious  to know what percentage of these Phase I patients are achieving either Very Good Partial Response (VGPR), near-Complete Response (nCR) , or Complete Response (CR).  I'll explain these criteria in a later post.


Another issue that has been bothering me for a while is how to interpret the M Spike value versus my total IgA gamma globulin value.  I have searched the Internet fruitlessly for a straight answer to this question.  The M Spike from the SPEP test supposedly estimates the amount of the malignant monoclonal protein (mine is IgA Kappa).  This value is reported to two significant figures in units of g/dL.  Here is a picture of how this looks:


The SPEP test doesn't identify the specific type of globulin in the M Spike.  The corresponding Immunofixation Test gives the breakdown and amounts of all the immunoglobulins, including the total amount of IgA.  These values are reported to four significant figures in units of mg/dL.  Now why would the units and number of significant figures in the reported test results differ?  My simple mind tells me logically that subtracting the M Spike value from the IgA value (in comparable units) should give the amount of good polyclonal IgA floating around in there.  I asked Dr. Paba-Prada about this.  Her answer was that they measure different things.  Hmmmm.  I was underwhemed.  I know the objective is to get the M spike to zero and all the other immunoglobulins back into their normal ranges.  That's nice, but it doesn't answer my question.  You haven't heard the last of me on this issue.

I have to warn you that I got my induction doses of MLN 9708 and dexamethasone today.  I think the dex is starting to kick in, so I might just go on here for a while.  Feel free to take a break and go get a cup of coffee or a tall one, depending on what time of day you're reading this.

Our visit with Dr. Richardson was awesome, as usual.  As for the Zometa issue, he wants me to get started on this (via IV), but he is not in an all-fired hurry, and he would like me to get my oral surgery crap out of the way first, which I hope to accomplish this month.  Next month, I hope to be able to tell him with my new gap-toothed smile that I'm ready to go!

My biggest question has been how to deal with the potential timing of a stem cell transplant.  Assuming continued good progress, Dr. Richardson is of the opinion that I should stay on this current protocol, with an interruption around Cycle 4 to harvest my stem cells.  At that time, I will undergo stem cell mobilization using cyclophosphamide chemotherapy.  My stem cells will then be harvested for future use, and the current plan is for me to go back onto the MLN 9708 protocol and complete the full 12 cycles.  I was hoping he would recommend this approach.  Ideally, I will have a Complete Response (CR) or even better, a stringent Complete Response (sCR) and be in remission.  Of course, at some point, relapse is inevitable.  Since I will likely be in my 70s by then (I sure hope so!), a reduced rather than a full ASCT would be performed.  Anyway, the idea here is to kick the can down the road, and who knows by that time what miracle MM drugs and possible cures may be emerging.

Overall, Dr. Richardson and his team are very pleased by my progress to date.  Of course, the blood test results from Cycle 2 won't be back for 3 or 4 days, but my numbers so far look very good, and he thinks I look great.  I certainly feel great.  It was a very upbeat meeting, and Gretchen and I both left feeling very good.  We don't expect all the meetings to go this well, but we'll take it while we can.  We decided to celebrate by having dinner at Petit Robert.  It was delicious, as usual.

Now look what I've done.  I've gone and rambled on, and now it's not today anymore.  It's tomorrow.  Which means we did all of this yesterday, not today.  I think it's time for me to go lie down and pretend to go to sleep.  If you don't read this in the next couple of hours, be pre-warned.  I might get back up again and this post could get even longer before I throw in the towel.

Another compatriot

Yesterday I played in a Teamsters golf tournament with my friend, Bobby.  (Don't ask how we did.)  Ed, one of the organizers of the tournament whom Bobby has known for years, didn't look quite himself, so Bobby asked his wife if he was OK.  Turns out he has Multiple Myeloma.  I guess the disease isn't so rare after all.

I had a chance to talk with Ed briefly.  He was diagnosed about a year ago,  As was the case with Chuck, he first noticed the effects of MM when he discovered that three of his ribs had broken.  Ed is seeing one of Richardson's other colleagues at DFCI.  He is just about to have an autologous stem cell transplant (ASCT).  The day before the tournament, he had gotten his first dose of heavy chemo to kill all the bone marrow cells.  When he took off his hat, he had already lost most of his hair overnight.  He will spend 3 weeks or so in the hospital undergoing this procedure.  This is not for the faint of heart.  I plan to keep in touch with Ed and see how he is doing.

When and if to schedule ASCT is one of the big decisions I may have to make in the near future.  I am hoping that I can continue on my induction therapy if it seems to be effective, and then move into a maintenance mode until a relapse sometime down the road.  However, I'm getting a little long in the tooth, and they don't like to do ASCT much after the age of 70, so there might be an argument for me to do it sooner rather than later.  I don't know.  I expect to start having this discussion with Dr. Richardson on Tuesday.

While perusing the Internet today, I came across a good blog from another MM patient, Pat Killingsworth.  He contracted MM in 2007 at the age of 51.  Pat then went through the same dilemma I may soon go through in deciding whether to get a stem cell transplant.  He elected not to, but this year, he suffered a relapse, so he had the ASCT this past summer.  One of his blog entries is particularly interesting, as it focuses on providing basic information for newly-diagnosed MM patients.  I thought I would share this with you, since it is a straightforward discussion of a highly technical and confusing topic:

http://www.multiplemyelomablog.com/p/helpful-information-for-newly-diagnosed.html

I hope you find it informative.

By the way, my blood tests from last Tuesday all have come back.  I'm not quite sure how to interpret all of them, but I noticed that my total protein is down to the lowest level since I started at 5.9 g/dL.  My albumin has been hanging steady near the bottom of the normal range at 3.7 g/dL, but my globulin level has dropped from 2.8 to 2.2 g/dL since Aug. 30.  My hope is that this reflects a further reduction in my M spike, which was 0.41 g/dL on Aug. 30.  Of course, I won't know until my SPEP tests come back late next week, but I'm hopeful!

FISH test and Chuck

When I had my first bone biopsy back in April, my biopsy sample was sent to the Mayo Clinic for chromosome analysis using Flourescence in situ Hybridization (FISH).  FISH testing serves as a screen to prognostically stratify the risk of MM patients.  My results came back with one favorable indicator and one unfavorable indicator.  The positive indicator was a chromosome addition, called hyperdiploidy.  However, the negative indicator was a translocation between chromosomes 4 and 14, called t(4;14).  Unfortunately, the unfavorable indicator trumps the favorable one, so overall, my situation has to be considered high risk.

Studies have shown that patients with t(4;14) tend to have poor overall survival and short remission times.  This knowledge has been weighing on my mind for some time now.  However, one of the interesting presentations at the MMRF Patient Symposium we recently attended addressed this issue.  Dr. Munshi, a colleague of Dr. Richardson at DFCI, gave a presentation where he indicated that the more recent front-line drug treatments, including Velcade and Revlimid, may partially overcome the t(4;14) risk factor.  This seemed like good news, so I wanted to follow this up with Dr. Richardson when we meet with him next week.

I have a few other questions that I want to discuss with my medical team on Tuesday, so I decided to send Dr. Richardson and his team an email today with my list of questions, including the t(4;14) issue.  To my delight and surprise, Dr. Richardson answered my email within 20 minutes!  He said I am doing great  (yahoo!), and he immediately answered the t(4;14) question by saying that the MLN 9708 is equivalent to the Velcade, and the Revlimid can overdrive the t(4;14).

This is really good news!  As if I don't have enough reasons to be grateful that I am included in this clinical trial, it appears that I am also getting the best available combination of drugs to mitigate my most important negative MM risk factor.  So far, I feel I have been very fortunate in every aspect of dealing with this disease.

This point was driven home to me even more so today.  One of the people we met at the symposium, Sharon, has a husband with MM who couldn't attend that day because of his painful peripheral neuropathy.  Gretchen called Sharon today, and I had an opportunity to spend some time on the phone with her husband.  Chuck was also recently diagnosed with MM this past May.  However, by the time he was diagnosed, he had severe MM symptoms, including three broken ribs, multiple bone lesions, and severe anemia causing breathing problems.  For whatever reason, he didn't have the opportunity to enroll in the MM 9708 clinical trial, so he got started on the Velcade/Rev/dex initial induction therapy.  Unfortunately, he quickly developed severe peripheral neuropathy, which is one of the common side effects of Velcade.  Chuck now has a lot of pain in his arms and legs, to the point that he can barely function.  As I mentioned in a previous post, the MLN 9708 does not seem to have Velcade's side effect of peripheral neuropathy.  I have had no symptoms whatsoever to date.  It's too late for Chuck to get into the MLN 9708 clinical trial, so he has to continue the treatment he is on.  I really feel bad  for him.  I hope Chuck can find some relief from his pain.  I can't help but think that I could just as easily be in his situation.  So far, I'm counting my lucky stars.

Bisphosphonates and me

You may recall in my first blog post that Dr. Richardson has suggested that I take Zometa, which is a bisphosphonate, to help build my bones back up, having been weakened somewhat by the MM.  Zometa is his metaphorical Coast Guard drug, which will help protect the Homeland, while the trio of clinical trial drugs (Army, Air Force, and Navy) are fighting off the foreign invasion of nasty old myeloma cells.

One tiny little eensy weensy problem with bisphosphonates is that they can cause a rare but serious side effect called osteonecrosis of the jaw (ONJ).  In order to minimize the potential of this, one should not undergo any serious dental work (root canals, extractions, etc.) while taking the drug.  So I went to the dentist for a checkup.  Unfortunately, my dental history is far from stellar.  My last visit to the dentist was six years ago to get a root canal.  It now appears that I have another seriously decayed tooth (supporting a bridge) which may either need a root canal or have to be extracted.  And the root canal I had in 2005 may need more work.  (Ask me why I'm going back to the same guy.)  Anyway, I have an appointment for next week to sort this all out.

I was somewhat curious about this ONJ, so I went online to check it out.  Here are some of the pictures I ran across:
                                                    

              

 Holy crap!  Yeeeeewwww!  Grotey to the max!  HOW DISGUSTING!

To hell with the Coast Guard...I do not ever want to be in one of these pictures.  Depending on what dental work I need to have done, Dr. Richardson and I are going to have a good heart-to-heart talk about this before I decide to start taking Zometa.  Stay tuned.