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Friday, July 27, 2012

Hiccup, Not a Glitch

After suspending treatment last Friday because of low blood counts, I went into DFCI on Tuesday hoping that I had recovered enough to resume the Vel/Rev/dex therapy.  It was not to be.  Despite my having skipped the Velcade on Friday and stopped taking the Revlimid, my numbers were actually worse on Tuesday!  My white blood cell count (WBC) dropped from 2.4 to 1.8, and my absolute neutrophil count (ANC) went down from 994 to 750.  Gulp!  At least I hadn't become officially neutropenic, which is when the ANC drops below 500.

I was obviously disappointed.  Again, my Velcade infusion was skipped and I was told not to take either the Revlimid or the dexamethasone until my neutrophils have recovered.  To help this process along, I got a shot of neupogen to stimulate white blood cell production.  Muriel Gannon reassured me that this is a very common problem, and it is just a hiccup, not a glitch.  She was pretty sure the problem is due to the Revlimid, not the Velcade.  This surprised me at first, because during my induction therapy, I was taking 25 mg of Rev without any problems.  Now I am only taking 15 mg.  Muriel said that the reason is my stem cell transplant.  My body still hasn't fully recovered and I am more sensitive to the drug side effects.  I guess that makes sense.

I immediately put all this behind me as I drove directly to Dartmouth, MA and embarked on a relaxing two-day sailing adventure with my friend, Lew.  We moored his boat for the night in Cuttyhunk and watched the beautiful sunset as we ate oysters on the half shell delivered to our boat and grilled filet mignons for dinner.  Not too shabby!  Lew makes a mean martini, which I have to admit I imbibed, but don't tell Dr. Richardson.

The next day, another friend, Sam, came over on the ferry, and we sailed to Menemsha on Martha's Vineyard, where we picked up some harpooned swordfish (yum!).  Dinner that night was even more delicious, if that's possible. We all went swimming, but I have to say that on a relative scale, I would rather have an IV stuck into my arm than dunk my whole body into the cold Massachusetts ocean.

I came back home yesterday, happy but exhausted, and collapsed until this morning.  I went back into DFCI with my fingers tightly crossed, hoping for the best.  I guess the neupogen shot did the trick, as my WBC has jumped up to 7.7 and my ANC skyrocketed to 6,160!  Now, I am back on the consolidation therapy, but my Revlimid dose has now been reduced from 15 to 10 mg going forward.  I have next week off before going into the final cycle of my Vel/Rev/dex consolidation protocol  I hope there are no more glitches, hiccups, or whatever to contend with as this therapy continues.

Monday, July 23, 2012

Minor Glitch

Last Friday, we went into DFCI for my blood draw and infusion of Velcade planned for Day 4 of Cycle 3.  However, it didn't work out that way.  One of the numbers they monitor closely during treatment is the absolute neutrophils count (ANC).  Neutrophils are white blood cells that protect against infection.  Since the previous Tuesday, my ANC went from 2,610/uL to 940!  The cutoff threshold for a safe level is 1,000.  As a result, I didn't get my Velcade push Friday, and I was told to stop taking the Revlimid as well until I go back again on Tuesday.

This was a bit disconcerting, as this has never happened to me in the past.  The only time my ANC went below this was during my stem cell transplant, when it basically went to zero before my new stem cells rebuilt my immune system.  However, Heather told us that this is a very common occurrence and not to be concerned about it.  Still...  I have to keep in mind that these are powerful chemo agents and that there is nothing routine about this therapy.  Hopefully, everything will be copacetic by my next appointment tomorrow.

On the positive side, there was some good news that came out on Friday.  The FDA granted accelerated approval for Kyprolis (carfilzomib) as a new treatment for patients with advanced Multiple Myeloma.  Kyprolis is a proteasome inhibitor in the same class of drugs as Velcade and MLN9708.  It is the first MM therapy drug approved by the FDA in the last six years and will hopefully be a harbinger of more drug approvals to come.  This is another potential weapon in the arsenal against MM.  I hope I won't need Kyprolis any time soon, but it sure is nice to know that it will be on the shelf if I do.

Today I had a followup visit with the orthopaedist to monitor my recovery from the ladder incident.  Fortunately, the broken bone in my hand is healing fine and there is no residual rotator cuff problem in my left shoulder.  My muscles are still a little sore, but that is normal, as they tend to heal slowly, so I came away with a clean bill of health.  I am one lucky duck!

After my DFCI appointment tomorrow, I am off to sail on the bounding main for a couple of days with my friend, Lew.  I am really looking forward to this, especially since I didn't do Block Island Race Week this year for the first time in twenty years.

Wednesday, July 18, 2012

Consolidation Cycle 3 Update

Yesterday I started the third cycle of my Vel/Rev/dex consolidation therapy and we met with Dr. Richardson.  My blood test numbers improved nicely from the last two weeks due to my 1-week holiday from the Velcade and Revlimid.  My WBC went up from 2.6 last week to 4.2, and my platelets rose from 83 to 166.  Both are now back in the normal range.  The only nagging area that doesn't improve over time has been my anemia (Hgb and HCT are consistently low).  I've been a little tired lately, which could be partly due to the anemia, but Muriel said that this is normal and that most patients suffer some fatigue while on the consolidation therapy.  Other than that, I'm doing fine.  I won't get the blood and urine phosphoresis and immunofixation results until next week, but those results have been improving steadily since my ASCT.

Muriel Gannon and Paul Richardson both said that I am doing great!  We also ran into Kathy Colson, who was the head nurse on the MLN9708 clinical trial.  She said that these trials are still going great with 98% overall response rate, which is extremely good.  She also said that I am still the "poster child" (so to speak) for how well this drug is working.  Nice!

While meeting with Dr. Richardson, I had a chance to ask about some of recent research I have been posting on lately.  My first question was on the recent Actemra (tocilizumab) paper showing the improved M-Spike in the patient being treated for Rheumatoid Arthritis who also had Smoldering Myeloma (SM).  He was very interested in this paper, so I gave him a copy.  He felt it might be significant, since it is well known (but not by me) that IL-6 is a particularly important enabling factor in precurser forms of MM (MGUS and SM), more so than in active MM.

I also asked him why MM research on Actemra seems to have dried up so quickly.  I gave him an excerpt from another paper co-authored by his boss, Dr. Ken Anderson, in 2011 extolling the virtues of tocilizumab as an anti-IL-6 agent (see Section 3.2):

Antibody-Based Therapies in Multiple Myeloma

His answer was very informative but a bit oblique.  He said that trials for the anti IL-6 monoclonal antibody, elotuzumab, are showing excellent results (OK, that's good).  Another antibody, daratumumab, has been effective against MM by binding to CD38 on the MM cell (that's good too, but it's not IL-6).  A third anti-IL-6 antibody, siltuzumab, has not been shown to be effective (too bad, but doesn't that strengthen the case for studying Actemra?).  All this was very interesting, but he didn't quite answer my question.  I didn't pursue it further, but I might bring it up again next time.

I also asked him about the other paper I blogged about recently regarding finding the RNA component, ACA11, which is found to explain the poor prognosis for high-risk t(4;14) patients.  Richardson has a high opinion of the author, Michael Tomasson, from Washington University in St. Louis, and said he is a good researcher.  That's encouraging, but when I asked him whether this would be a fruitful area for research, his response was pretty much what I expected.  He said that since Velcade and Revlimid both overcome the high-risk prognosis of t(4;14), he doesn't see it as a high priority now.

"But, but.", I was tempted to ask, "If I become refractory to these agents, what would I do then?"  I guess this is a question for another time.  Hopefully, I will never need to ask it.

Friday, July 13, 2012


One year ago today, Gretchen and I met with Dr. Richardson at DFCI for the first time.  During our session, he responded to my question with these fateful words that changed our lives forever:  "You have Multiple Myeloma".  From that instant on, I became an MM patient and Gretchen became a caregiver.  Nothing would ever be the same again.  And so began our journey.

One year later, I can look back at a remarkable year.  It's hard for me to believe how fortunate I have been.  I was diagnosed early with Stage 1 MM, with my only symptom being anemia.  I had no bone destruction or kidney issues to deal with.  On that first day, I got the opportunity of a lifetime to participate in the MLN9708 clinical trial.  I jumped at it.  It worked beautifully, and after 6 cycles, I had achieved CR.

I struggled mightily with the decision to undergo a stem cell transplant, but again I had the opportunity to participate in an important clinical trial.  I underwent the ASCT in March, and while it was no picnic, I responded well and recovered quickly.  I drew what Dr. Richardson considers the best random arm of the trial, involving both consolidation and maintenance therapy.  I am now half way through the Velcade/Revlimid/dexamethasone consolidation phase.  I am still in CR, and so far have not suffered any of the feared peripheral neuropathy side effects from the Velcade.  So far, so good.

There have been a few rough patches along the way.  Last fall I contracted  cellulitis, which required serious IV antibiotics to control.  I have also encountered occasional bouts of low energy, fatigue, and/or diarrhea.  Of course, my latest self-inflicted trauma from the ladder incident didn't help.

It has taken quite a bit of adjustment for both Gretchen and me to deal with our new reality.  Anxiety and uncertainty are never far from our minds, and being tethered to DFCI has defined our schedules for the past year.  Overall, however, I have no complaints.  My health now is better than I could have dared hope one year ago today.  We are blessed, and we are grateful.

Expanding on my last post on cancer research, my fellow patient friend, Steve, recently sent me an article about an existing drug used to treat Rheumatoid Arthritis (RA) which might have some benefits for MM.   Here is a link to the abstract:


A patient with both RA and Smoldering Myeloma was given the anti-RA drug, tocilizumab (trade name Actemra), and surprisingly, her M-Spike went down.  Tocilizumab helps block the protein Interleukin-6 (IL-6), which causes inflammation in RA.  IL-6 is also a bad guy in MM, as it stimulates the proliferation of the myeloma cells.  So far, attempts to control IL-6 in MM have been unsuccessful.  Here is an example where cross fertilization between different medical specialties may speed the development of new treatments. Could tocilizumab be a possible miracle drug for MM?  Is anybody actually looking at this?

Tuesday, July 10, 2012

Cancer Research

I'm tempted to say that this is an exciting time to be diagnosed with MM, but that's not exactly true.  I wouldn't call having MM really exciting in any way.  However, the landscape has changed dramatically in the last 5 to 10 years, and there is now a lot more reason to be hopeful for extended remission and even possibly a cure coming down the road.

The recent ASCO conference in Chicago unveiled a number of promising new therapies that have been successful against a number of cancers.  While there were no dramatic breakthroughs for MM, there is a lot of cross fertilization, where an an agent successful against one cancer might be useful in another.  Basically, current research efforts are focusing on more individualized and targeted therapies, based on more detailed diagnoses using sophisticated tests, as well as genetic profiles.

This past weekend, an old high school friend of mine, Ken, sent me an article that ran in Sunday's New York Times.  (Ken's not that old, but he's a bit older than I am, which I am fond of reminding him.)  Here is the link:  Genetic attack on cancer shows promise.  This is a case where a cancer lab researcher contracted acute lymphoblastic leukemia and was dying.  His lab colleagues went to work sequencing his genome and RNA and found a rogue gene that was spurring the growth of his cancer.  Fortunately, there was a drug available that was approved for kidney cancer that worked on that particular gene.  He was the first person to take it for leukemia and his cancer is now in remission.

Last week I came across an interesting paper referenced in the Myeloma Beacon regarding a culprit behind the t(4;14) high risk MM.  Of course this is of particular interest to me.  Here is a link to a discussion about this paper:  Culprit behind chemo resistance to t(4;14).  What they found is that there is a particular genetic RNA component in t(4;14) patients, called ACA11.  This RNA gene allows the cancer cells to grow better and be resistant to chemotherapy.

This is great news!  While there may not yet be a drug available that can specifically attack this ACA11 genetic RNA aberration, this is an important clue telling researchers where to look.  As the summary to this article explains, “Now we have an angle for just focusing on the drugs that we know work better, as well as on experimental approaches for these patients,” he says. “It gives us a new way to study how we can improve their care.”

Fortunately, Velcade and Revlimid both seem to be chemo drugs that work effectively on t(4;14) patients, such as myself.  However, if researchers can find a mechanism to shut down the ACA11 effect, it can only be to the benefit of all of us t(4;14) patients.

I think the future of cancer research in general and MM research in particular will be to isolate specific genetic sources of the cancer, and then find targeted drugs to specifically attack these rogue genetic aberrations.  There have already been some successes, but to really push the envelope here, genetic sequencing will have to become less expensive and more available as a routine diagnostic procedure.  Then, it will become easier to identify specific genetic cancer markers and concentrate on finding drugs to neutralize their effects. 

I am very hopeful that all these research efforts will prove to be successful during my lifetime. 

Thursday, July 5, 2012

Immunofixation Fixation

As you know, I have been somewhat fixated on my immunofixation results lately.  Prior to my stem cell transplant, my blood serum protein electrophoresis (SPEP) results showed "no M-spike detected", and the more sensitive corresponding immunofixation results showed "No monoclonal gammopathy".  Those were great results from my induction therapy with the MLN9708.

However, since my stem cell transplant, these test results have been more problematic.  Starting in May, I noticed that the immunofixation results started showing "a faint M-spike that cannot be quantitated" and "Double gammopathy with free Lambda protein".  This is when I questioned Richardson and was told that after a transplant, there are spurious test results that are not clinically significant.  OK, fine.  However, on May 22, the interpretation got more ominous, with the result, "Double gammopathy with IgG Lambda paraprotein."

That's when I freaked out and found that my initial diagnosis a year ago showed an IgG Lambda component of MM, along with the dominant IgA Kappa.  My next test result from June 5 showed the same results.  That's when I wondered whether this was lurking in the background to take over once the IgA component was vanquished.  As I mentioned in my last post, Dr. Richardson still feels there is no clinical significance to these results.

I can get most of my test results online using the DFCI Patient Gateway.  That is very helpful and informative, but unfortunately, it doesn't include the SPEP and Immunofixation pathology reports.  I have to get printouts of those the week after the blood tests.  This past Tuesday, when I went in for my infusion, I got the pathology report from my most recent June 26 SPEP test.  The immunofixation test still shows a faint M-spike, but the interpretation is now back to "Double gammopathy with free Lambda paraprotein".  The IgG component is now gone!  Whoopeedoo!  I don't know if this is due to the effect of my Vel/Rev/dex consolidation therapy or whether it's just going away by itself, but either way, I'm happy about it.  Obviously, I will continue to track this closely.

After my clean bill of health from the dentist, Dr. Treister, I received an infusion of the bisphophonate, Zometa, on Tuesday.  I will continue getting these infusions monthly, which should help build up my bone strength.  Fortunately, my bones must be in pretty good shape to start with, considering how well they survived my fall off the ladder.

Speaking of that, I am still recovering nicely from the fall.  The aches and pains are slowly subsiding, and I am starting to get back to feeling pretty good most of the time.  I've been sort of a bad boy and haven't scheduled the physical therapy my orthopaedist wants me to undergo.  My shoulder is actually feeling pretty good, so I don't think I need it.  Maybe I'll do it next week if I think about it.  Naughty me.

Sunday, July 1, 2012

Consolidation Cycle 2

This week I began the second cycle of my Vel/Rev/dex consolidation therapy.  I met with Richardson on Tuesday and questioned him on the significance of the trace amounts of IgG Lambda M Spike found in my recent immunofixation tests.  He reaffirmed to me that he felt it was of no clinical significance, so I guess I'm somewhat mollified.  It still bothers me in the back of my mind. however.  If this doesn't go away soon, I'll be bringing it up again, mark my words.  He also suggested that I start using Dr. Katz Therabreath mouthwash daily as a prevention against infection.  (He reassured me that it's not because I have bad breath, although who knows, maybe I do.)

I've been fortunate that I still have had no symptoms of peripheral neuropathy (PN) since starting the new treatment regimen.  I have a prescription for Neurontin (gapapentin), which helps PN, but I'm waiting to fill it in case I need it.  At the first sign of PN, I will start the gapapentin and request lowering the dose of Velcade.  I still hope to persuade Richardson to allow me to go to subcutaneous Velcade if PN rears its ugly head, but maybe that won't be necessary.

Wednesday, I went back to the othopaedic surgeon for a followup visit.  The broken metacarpal in my left hand is healing nicely and the dislocated pinky finger is doing fine.  My upper body was still pretty sore, which he said was normal.  I have some pain in my left shoulder from moving my arm, which he thinks might be a strain of my rotator cuff muscle, so he prescribed 4 weeks of physical therapy and wants to see me after that.  I haven't scheduled the PT yet, so I may start that tomorrow.

My body is slowly healing from the abuse I subjected it to.  It's not letting me forget this incident too quickly, which is probably a good thing.  Each day is slightly better than the one before.  I still find that I like to rest in a comfortable position as often as I can.  Excuse me while I go lie down for a bit...

...OK, I'm back.

Friday, I had a followup visit with Dr. Treister, the dentist at Brigham and Women's Hospital.  He had expressed some lingering concerns before my stem cell transplant about all the dental work I had done last fall.  Just in case your have forgotten, one of the issues with the bisphosphonate, Zometa, is the potential for osteonecrosis of the jaw (ONJ), as I reported on in my post of Sept. 19, 2011:  bisphosphonates-and-me.  Just to be safe, Dr. Paba Prada wanted me to get a clean bill of health from Treister before resuming my Zometa treatments.  After examining me, Triester said everything looks fine, so I should start back on a monthly schedule of Zometa infusions, probably starting this week.

I hope everyone has a happy 4th of July holiday!