Year End

This has been a tumultuous year.  Gretchen's accident has been the major story of the year for us.  Thankfully, she has recovered amazingly well from her terrible injury, but of course things won't ever be quite the same for her.  However, she is adjusting to her "new normal", and for those who don't know her well, they would not even notice any difference.  Compared to where she was on that terrible day in February, it's a miracle that she has recovered as well as she has.  She is very lucky, and so am I.

As for myself, I am grateful that I have continued in remission from MM.  It will be two years in March since my stem cell transplant, and so far I feel terrific.  Of course, this is month-to-month, and I keep waiting for the "Sword of Damocles" to eventually fall.  But until then, yay!

We have had a wonderful Holiday Season, albeit a bit stressful.  We were blessed to have the whole family visit us over Christmas.  Holly and Ryan flew in from San Francisco on the Saturday before Christmas.  Then Brian, Pam, and our 3-year old grandson, Logan, drove up from New Jersey on Christmas Eve.

Logan and Sophie

Friends and family, including Jeff and his girlfriend, Christine, celebrated here on Christmas Eve, as we savored pasta and our traditional ham.   It was a real treat to experience the excitement of Christmas morning as Logan opened his gifts from Santa.  Everyone, including Jason, was here to enjoy Christmas day.  A feast of roast prime rib rounded out the day.  It couldn't have been better! 

Over the past ten days, our fireplace has been constantly ablaze, as the winter weather has enveloped us.  As in days of yore, the hearth has drawn our family together over these holiday times.  We probably went through a half a cord of wood, but it has been so comfortable and satisfying for us to all gather around the fire and savor our time together.

Yesterday, Jeff, Brian, Christine, and I all went to the Patriots game against the Buffalo Bills.  The weather was terrible, but we had a great time tailgating with Ryan and his family. Despite the torrential downpour of rain during the game, we had a great time, especially since the Pats pulled out another win.

As wonderful as this was, I'm getting a little old to spend a whole day braving the elements to tailgate and watch a Patriots game while freezing my ass off or soaking to the bone and then spending another two hours or more fighting traffic to get back home.  Know what I mean?  I think I'll pass on trying to go to a playoff game this year.  A comfy seat in front of the TV beckons.

Today, everyone returned home, and we are now surrounded by a somewhat blissful silence.  Ah, the sounds of silence!  Tomorrow is New Years Eve, and we have no plans.  There was a time when New Years Eve was a time of great excitement.  One year as a child, I wanted to stay up for midnight, but my mom made me go to bed.  I lay awake in an excited state until the bewitching hour, when I got up and went downstairs to celebrate somehow. My mother, who was still up, said "So what do you want to do?"  So I decided to go outside and celebrate by throwing a snowball at midnight.  God!  What a dork I was.

As an adult, I used to host New Years Eve parties for many years.  Wahoo!  But times have changed.  Now, I no longer have any desire to stay awake to ring in the New Year.  I mean really, what is the difference between 11:59 and 12:01?  Nada!   I expect we will be in bed long before that witching hour.  Goodnight everyone, and have a Happy New Year!

More on Patient Symposium

One of the interesting presentations at the Patient Symposium (Irene Ghobrial) had to do with considering earlier treatment of Smoldering Multiple Myeloma (SMM) before it develops into full-scale MM.  The current standard of treatment is to do nothing until there is progression to MM.  On the average, SMM has about a 10% chance annual risk of progressing to MM.  However, there is a subset of SMM patients whose risk is much higher.  A clinical risk stratification profile has been established where:

• bone marrow plasma cells > 10%
• M-protein > 3 g/dl
• Free Light Chain Ratio (FLC) <.125 or >8 

Patients with these risk factors have a 50% chance of developing MM within 2 years.  Additional risk factors also indicate a quick progression from SMM to MM, including greater than 60% plasma cells in the bone marrow and t(4;14) cytogenetics.  I can testify to the latter, as I was diagnosed with SMM in May 2011, having both more than 60% plasma cells and t(4;14).  Two months later, when I met Dr. Richardson, it had already progressed to full MM.  Current research is exploring early treatment of SMM patients who exhibit these elevated risk factors.  Early clinical trials have been very promising in preventing these patients from progressing to MM.  More data is needed, but future therapy options are clearly headed in this direction.

Ken Anderson was his usual scintillating self in his presentation, discussing novel MM therapies.  He summarized one of the ASH presentations which demonstrated the overwhelming case for using Revlimid maintenance therapy after stem cell transplant, both in time to progression (TTP) and overall survival (OS).   Yay!  That's me.  He also predicted that because of the effectiveness of the new induction therapies, someday it may not be necessary to do stem cell transplants at all! 

As to future directions, Ken is really excited about the prospects for the monoclonal antibodies.  Trials with daratumumab and elotuzumab have been very promising to date, especially in combination with other drugs.  Also, the oral proteasome inhibitor, MLN-9708 (Ixazomib), that I helped to pioneer during its Phase I trial, is entering Phase III trials and may be on target for FDA approval in the next year or so.  Trial results continue to be excellent.  Because it is an oral drug, Ken feels that one day Ixazomib may become a standard for maintenance therapy.  He is also optimistic about the HDAC inhibitor, ACY-1215, which has shown excellent synergistic results in combination with Velcade, Len, and dex. 

Paul Richardson also gave an excellent presentation.  He reported on the latest ASH stem cell transplant research showing updated results from RVD induction, ASCT,  and RVD consolidation, followed by Rev maintenance.  The results showed that consolidation therapy before maintenance upgraded the response rate by 26%!  That's the path I am on in my ASCT clinical trial.  Obviously, Paul must have known this when I got randomized for the trial, as he told me when I was selected that I was on the best arm of the trial.  I wonder if he had anything to do with my getting selected for this arm.  Hmmm.  In any case, thank you Paul!

Richardson also expounded on the continued proven benefits of carfilzomib (Kyprolis) and pomalidomide (Pomalyst) presented at ASH for relapsed MM, even for those who became refractory to Velcade and/or Revlimid.  This is great news to those of us looking forward to the options that may be available to us when we eventually relapse.  Results with these agents have been so good that future regimens may evolve so that carfilzomib/pomalidomide/dexamethasone (Car/Pom/dex) may someday become the standard front-line treatment for MM.

Paul also presented detailed followup on the latest Ixazomib trials, which continue to show outstanding results.  I'm really happy to have had the privilege of participating in the initial Phase I trials of this amazing drug.  He also presented results bolstering his bias to early ASCT rather than waiting until first relapse.  Finally, he presented excellent recent clinical trial results using the monoclonal antibody daratumumab along with Len and dex in relapsed or refractory MM patients.  The results are very encouraging, suggesting further clinical development.

Sorry for the plethora of technical details in this blog post, but I wanted to do a data dump of what I learned on Saturday before it all faded from my memory and/or I could no longer decipher my cryptic notes.

Patient Symposium

Yesterday I attended the annual MM Patient Symposium at the Farber.  As usual, it didn't disappoint.  The Farber staff updated us all on the latest developments in the battle against MM, including the latest results from the ASH meeting last weekend in New Orleans.  There were a lot of encouraging developments that I would like to share with you.

But first, I want to talk about the people I met at my table.  Tom sat next to me, and his wife was in Brigham and Women's Hospital (BWH), having just got her ASCT on Tuesday.  He was from upstate New York (Lake George) and was staying here while his wife went through this ordeal.  She was recently diagnosed last summer, and she also shares my t(4;14) high-risk factor.  We talked about how scared she is and all the bad stuff she reads online about how little time she may have to live.  He was really upset that she is terrified about what she's read on the internet and worries that she won't be alive to see her newly born grandson learn to walk.  I told him to tell her that as long as she's on Velcade, her worries are overblown.  "Look at me", I said.  "I'm going on over 2 and 1/2 years, in remission, and doing great."  I suggested that she ask her doctor (Schlossman) about his prognosis.  I guess she's been afraid to ask the question up to now.  I told Tom that Paul Richardson told me on my first visit that I would live into my eighties.  She needs to think positive!  I directed him to my blog to share with her.  I hope she finds encouragement from my experience.

Then there was this delightful couple from Worcester, Betsy and Joel.  They were there because their 22-year old son, Ethan, a senior in college, was just diagnosed in July with MM.  Really!  He in undergoing the usual RVD induction therapy and is scheduled for a stem cell transplant next month at BWH.  I think it sucks that I have MM, but come on now, for a young kid like that to have MM,  that's beyond the pale!  Betsy and Joel were very concerned about the ASCT and wanted to know what my experience was like.  I shared my story and told them how great BWH is and that I had no problems at all.  I also reassured them that this should be a piece of cake for someone as young and strong as he is.  I also shared my blog address with them so they could check out my experience.

Today I got an email from Betsy.  They checked out my blog and found that they had already read some of it!  As it turns out, Ethan was very ill with Lyme disease several years ago, and they thought that somehow the Lyme disease might somehow be related to the MM.  Join the club!  They had asked Schlossman about the potential relationship between Lyme and MM.  His response was that that question has been raised but there is not enough data to validate it.  It's interesting that this interaction seems to come full circle.  The Lyme/MM connection just doesn't seem to want to go away.

I have lots of notes from yesterday's session.  There are great results from continuing clinical trials with Kyprolis, Pomalyst, and MLN-9708, as well as with monoclonal antibodies (elotuzumab, daratumumab) and HDAC inhibitors (panobinostat) .  Recent advances may lead to potential immunization therapies in the future.  Research also continues to connect genetic profiles with potential treatment regimens, with the goal of providing individualized treatments.  These latter developments may be years away, but in the meantime, the multi-drug therapy options continue to expand and show dramatically improved results for both newly-diagnosed and relapsed patients.  It's a very promising landscape for future treatment options.

I'll expand on some of these in a future blog post unless I forget.  You know how it is at my age.

ASH Conference

This past weekend, the American Society of Hematology (ASH) held its annual meeting in New Orleans.  The buzz leading up to the conference indicated that there wouldn't be any new blockbuster breakthroughs in treating MM to announce.  Unfortunately, that proved to be the case.  Not to say that there hasn't been significant progress, however.  Some of the new therapies continue to show positive results, and they are moving closer to the point of being able to provide targeted therapies for individual cases.  In the meantime, a number of new drug therapy options are being explored, which should provide a variety of future options for those of us who will eventually relapse.

This Saturday, I will be attending a patient conference at the Farber, where Drs. Anderson, Richardson, and others will summarize some of the recent advances, including those presented at ASH.  I hope to get a better feel about the more promising developments in trying to control or cure this disease.  I will provide an update on what I learn at this symposium.

I just read an interesting article in the Myeloma Beacon about MM risk classification.  The Inter­national Myeloma Working Group (IMWG), recently released a consen­sus statement on risk stratification for patients with multiple myeloma.   Here is a link to the article:  risk-stratification-multiple-myeloma.  Here is a quote summarizing the gist of the article:

"In the new system, determination of a patient’s risk classification is based on three factors: a patient’s disease stage according to the Inter­national Staging System (ISS); the presence of certain chromosomal abnormalities in the patient’s myeloma cells based on results of so-called FISH testing; and patient age.

Patients who are ISS stage II or III and whose myeloma cells contain the trans­lo­ca­tion t(4;14) or the deletion del(17p13) are classified as high-risk. About 20 per­cent of patients are expected to fall in this category at the time of diagnosis, with median overall survival of two years from diagnosis.

Patients who are ISS stage I or II, under the age of 55 years, and whose mye­lo­ma cells do not contain t(4;14), del(17p13), or 1q21 gain are classified as low-risk. About 20 percent of patients also are expected to fall in this category at diagnosis, with median overall survival of more than 10 years from diag­nosis.

The remaining 60 percent of patients are classified as standard-risk, with median overall survival of seven years from diag­nosis."

When I was first diagnosed, I was classified as ISS Stage I, which puts me into the standard risk category.  However, my b2-microglobulin was just a fraction below and my albumin was just a fraction above the thresholds of my being classified as ISS Stage II.  As you can see from the above, with my t(4;14) translocation, had I been classified as ISS Stage II, I should be dead by now! 

But I take heart from a number of considerations.  First, I believe I caught my MM just in time.  Just two months earlier, I had been diagnosed with Smoldering MM.  Fortunately, I managed to get an appointment with Richardson just as my MM was rapidly developing.  If I had waited a few more months, I may have been a solid Stage II and my prospects might have dimmed considerably.  Second, I was fortunate to nail the right induction therapy with the clinical trial using MLN-9708, which put me into a stringent Complete Response (sCR) after 7 cycles.  Third, recent studies have shown that use of Velcade (and I assume MLN-9708) along with Revlimid help to mitigate the high-risk effects of the t(4;14) translocation, which further helps push me into the standard risk category.  Because of the rapid advances in treatment options, I consider the current standard-risk 7-year Overall Survival (OS) to be low.  So I'm projecting at least 10 years for myself, the way I look at it.  The bad new for you is that you may be subjected to my blog for an interminable length of time.  So there!

On another positive note, the latest research shows that resveratrol, one of the major active compounds in red wine, may effectively kill myeloma cells!  Here's a link to the article in the Myeloma Beacon:  red-wine-resveratrol-and-multiple-myeloma-the-evidence-is-promising-but-needs-further-study.  I just poured myself a glass of red wine.  Cheers! 

Birthday Boy

Gretchen and I spent my birthday today at the Farber.  Woohoo!  One might think that there would be better places to celebrate one's birthday, but I don't think so.  Without the Farber, I might not even have been around for this occasion, so perhaps it's fitting that I could celebrate it at the place that has gifted me with more birthdays.  It has been almost two and a half years since my diagnosis with MM, and I am still going strong.  The next milestone will be March 20, the 2-year anniversary of my "second" birthday, the day of my stem cell transplant.

The blood test results today were good again.  Some of the numbers I was concerned about last month have bounced back, and there is still no sign of any monoclonal gammopathy.  I'm still feeling good, and I haven't been quite as tired lately.  Maybe that's because my anemia numbers showed some improvement this month.  In any case, I am grateful for my continued remission.  Happy Birthday to me!

Today, we had the pleasure of meeting with fellow patient, Dee, for lunch in the Farber cafeteria before her appointment with Dr. Richardson.  It was really helpful to exchange our stories.  Her expertise in scanning electron microscope (SEM) imaging is intriguing.  As a previous sufferer of chronic Lyme Disease (as was I), she thinks she has found evidence of the Lyme bacteria Borrelia burgdorferi (Bb) in her bone marrow samples using SEM.  Bb doesn't stay in the blood stream, as it burrows into various tissues in the body.  The available blood tests for Lyme can only check for antibodies that have been mobilized to fight the bacterial infection.  The only way to actually find the bacteria itself is to biopsy tissue samples, which has been done in some cases.  I think it would be really interesting and important to test bone marrow biopsy (BMB) samples for the possible presence of Bb in MM patients, as Dee has tried to do for herself.  There may be more sensitive means to do this than SEM, such as focus floating microscopy (FFM), but it would be worth trying to explore this potential connection in more detail.

It's intriguing to think that Bb can find its way into the bone marrow for Lyme Disease sufferers.  It's also intriguing to postulate that once it's there, this bacteria could trigger potential genetic mutations leading to MM.  Hmmm.  I'm just thinking out loud here (of course this is a figure of speech, as I'm writing not speaking, or would that be a "figure of text"?).

I know the medical community in general poo poohs any discussion or research into Lyme Disease for mysterious reasons that I'm sure have a lot to do with money.  But my prejudices aside, it might be difficult to have insurance companies pay for testing tissue samples for Bb without any established connection, so patients may have to shell out of their own pockets to have such a test done.

So the plot sickens.

Thanksgiving

So far, this has been a delightful holiday season.  Last weekend, we drove to New Jersey to visit with Brian, Pam, and our grandson, Logan.  We had a wonderful time!   We were then able to celebrate Thanksgiving at our house with sons Jason and Jeff, along with Jeff's girlfriend Christine and her mom.  The only ones missing from this holiday week reunion were our daughter Holly and her boyfriend Ryan, who are in San Francisco.  But they are coming back home for Christmas, when the whole family will finally be together, if only for a short while.

Yesterday, my college roommate, Steve, and his wife, Sue, came to visit and stayed over until today.  Some of you who follow my blog might recall some of his comments along the way, which he often signs OCRM  (Old College Room Mate).  Okay, Steve, you've just been outed!  We had fun reminiscing about the old days at MIT.  For some reason, most of his stories were usually at my expense.  Why is that?

Then today, to top it off, we got together with our close friends, Bobby and Cathy, and their family to continue our tradition of going to a local tree farm and cutting down our Christmas trees.  After that we celebrated in front of a roaring fire with hot chili and other treats.  Not too shabby!  I guess the Christmas season is now here.  It's time for us to be jolly and don our gay apparel (fa la la), but I don't have any pink shirts!

Monday, Gretchen and I are going into the Farber for my monthly blood test and Zometa infusion.  I am excited about being able to meet another MM patient there, Dee, who has an appointment with Dr. Richardson that day.  We have communicated before, and I wrote about her story in a previous post:  new-twist-on-lyme/mm-connection.  She has also suffered from chronic Lyme Disease, and I am anxious to learn more from her about her experiences.  I am slowly piecing together some of the stories I have gotten from a number of people about their experiences with Lyme or other autoimmune diseases and MM.  Dee has one of the more interesting stories, connecting with a rare disease, NXG. 

There was a story in yesterday's Boston Globe North Section about a local State senator, Brad Hill, who has recently been diagnosed with MM.  As it turns out, Dr. Richardson is his oncologist, and he is quoted several times in the article.  Here is a link to the article:  state-rep-brad-hill-stays-job-while-undergoing-cancer-treatment.  Paul Richardson is a big fan of metaphors.  When I was first diagnosed with MM, Paul described a coordinated attack on MM by the Army, Navy, Air Force, and Coast Guard, which included MLN-9708, Revlimid, Dex, and Zometa.  It was a very inspiring story as I sat in his office that first day, stunned with the realization that I had just been diagnosed with Multiple Myeloma.  He has also used the metaphor of a mongoose and a python, where aggressive early treatment puts the MM python in a basket, and further maintenance therapy is the mongoose that keeps the python in the basket.

In this Globe article, Richardson adds some more colorful metaphors to his MM repertoir, and I quote:  “The metaphor I use is that the stem cells are like salmon,” said Richardson.  “You catch them, and put them in the freezer, and you give them back to the patient and reinfuse them, just like a blood transfusion. The miracle of nature is these little guys, just like salmon, swim back to where they’re born, and regrow in the bone marrow.  Whereas Brad previously had, kind of, crabgrass in his bone marrow from the myeloma, after this chemotherapy all the crabgrass is wiped out. Then the little salmon come back, they repopulate the bone marrow . . . then you get Kentucky bluegrass.”

It's really comforting for me to know that I now have Kentucky bluegrass rather than crabgrass in my bone marrow.  I've always liked Kentucky bluegrass.

Farber Writing Workshop

I followed up my knee rehab appointment with another visit to my PT, Karen, last week.  It is quite apparent that the range of motion is noticeably limited in my right knee.  She left me with a full set of exercises that I can do at home and/or at the gym to help stretch and rebuild the muscles around my bum knee.  It's a good excuse to get back to the gym regularly after my "summer" vacation, which has now extended through most of the fall.

My visits to rehab have been a bit humbling.  First of all, Karen pointed out that I was bow legged, which puts more pressure on the inside of the knees, possibly accounting for my meniscus tear.  Okay.  Then she further volunteered that one leg is shorter than the other (I forget which one).  It seems that I'm coming up a bit short (so to speak).  I came out of there feeling like a deformed specimen of humanity.  All I need is a hump on my back, and I could pass for Igor from "Young Frankenstein".

Speaking of deformities, one of the things I forgot to ask Karen about is my L1 vertebra compression fracture, which may have been caused my my MM.  Are there specific exercises that would either help or hurt this condition?  I have found that lying flat on my back using a wooden yoga pillow under my lower back seems to help.  Here is what it looks like:

At first, it feels like a medieval torture instrument.  It takes a minute or two to relax into this posture while various vertebrae crack up and down my spine, but then it feels good.  It takes me a while to clamber back onto my feet after this contortion exercise, but afterwards, my back feels great.  I think this is a really helpful exercise, but I hope I'm not risking permanent disability or paralysis by my self-help therapy approach.  If I make to January without incident, I plan to ask Karen's opinion on this.

I went into the Farber today for the monthly meeting of the Writing Workshop that I have been attending for the last two years.  It was inspirational!  The people there have endured the pain and uncertainty of being either cancer patients or caregivers, and they all bring talent and creativity to the room.  They want to write for various reasons:  to document their difficult journeys, to help them remember things they might otherwise forget, to find an outlet to express their feelings, or to leave a legacy for their loved ones, to name a few.  It's amazing the clarity of purpose and zest for life that comes from knowing that one's time may be running out.  I really enjoy interacting with these special people.

Amy, the coordinator, is great at challenging us and giving us guidance.  At each workshop, she gives us a prompt, usually inspired by a poem, to write a piece addressing the prompt in only 10 minutes.  That's a challenge!  And then to read it out loud to the group?  Gulp!  Today, I couldn't believe the excellent pieces that rose to that challenge.  I came away from that workshop filled with energy and inspired to write.  I was determined to update my blog today.  So I did.

Rehab and Other Gab

I went to our mailbox today to post a letter that I wanted the mailman to pick up when he delivered today's mail.  When I checked the box, however, the mail had already come.  Drat!  So I picked up today's mail and drove to the post office to mail my letter.  When I got there, the letter had disappeared!  What?  I searched the car fruitlessly, so I drove back to the mailbox to see if I had dropped it along the way.  When I got there, I found the letter neatly nestled in the mailbox.  Duh!  Chemobrain?  Old age?  Some combination of the two?

I read recently that doorways are memory erasers.  I can purposefully walk from one room to another to accomplish something, but after going through the doorway, I stand there in bewilderment wondering why am I here in this room?  I'm sure this doorway theory has some merit, because I have a lot of experience with it.  I think the National Science Foundation should sponsor a study to verify this obvious conclusion.  I mean really, it makes sense, doesn't it?

Monday was my monthly Farber day.  Originally, I was scheduled to see Richardson, but the appointment was changed to see his nurse, Mary.  I did have a couple of questions for Paul about the potential Lyme Disease connection, so I was a bit disappointed.  On the other hand, I'm grateful that I'm doing so well that he doesn't need to see me on a regular basis.  That puts things into the proper perspective.

My pathology results from last month's serum electrophoresis and immunofixation tests continue to show no M-spike and no gammopathy, which is great!  So far, so good.  Some of my other numbers have slipped a bit, however.  My WBC dropped from 4.2 to 3.0, below the normal range, and my neutrophil count plummeted from 2.45 to 1.56, but still above the threshold of 1.0 where I would have to suspend taking the Revlimid.  My hematocrit also fell to 33.9, the lowest level in more than a year.  I just can't seem to shake this persistent anemia.  Oh well, at least I feel good, except for needing more sleep than I used to.

I asked Mary how long I should keep taking monthly Zometa (bisphosphonate) infusions.  She indicated at least two more years before moving to a 3-month schedule, because I need to build back my bones.  I knew I had severe osteopenia at the the time of my MM diagnosis, but I didn't realize until Monday that I actually have a compression fracture of the L1 vertebra.  That might explain why my lower back doesn't always feel so good.  Do ya think?

I finally went to the physical therapist for my knee on Tuesday.  I'm glad I went.  Karen, the PT, gave me a number of exercises to keep limber and build up the muscles around my knee.  I can do these exercises at home and at the gym.  I have to admit that I have been slightly remiss about going the gym lately.  By "slightly remiss", I mean I haven't been to the gym in about 4 months.  OK, OK...20 lashes with a wet noodle, as Ann Landers used to say.  Anyway, this should motivate me to get off my lazy ass and get back into the groove.  Fortunately, the cortisone shot is still working, and I don't even notice my knee most of the time.

I want to thank the goodly number of my readers who responded to my posts about the possible connection between Lyme Disease or other autoimmune maladies and monoclonal gammopathies (MGUS/SMM/MM).  There seem to be a lot of patients out there who have suffered the symptoms of chronic Lyme Disease some years before contracting MM or its precursors, some of whom have contracted other maladies along the way.  Of course, these anecdotal cases don't show a definitive connection, but I smell enough smoke to think that there's a fire there somewhere.  The real question is what is the mechanism for an overloaded immune system to trigger the mutations leading to myeloma?  Perhaps understanding this could help lead to better treatments or at least increased vigilance leading to earlier diagnosis.  I'm still soaking some of this in.  I'll update this blog with my conclusions, assuming I come up with any.

Richardson's Talk Radio Interview

While I was away last week, I missed Dr. Richardson's blog talk radio panel discussion.  Fortunately, I was able to access it when I got back and it did not disappoint.  He clearly established why he is one of the preeminent MM specialists in the world!  He addressed the question of when or if to do stem cell transplants in very direct and compelling terms.  He also addressed a number of related issues, such as consolidation and/or maintenance therapy after transplant.  For anyone who is interested in the entire episode, here is a link:  http://www.blogtalkradio.com/curepanel/2013/10/24/dana-farbers-dr-paul-richardson-discusses-myeloma

One of the major contributing factors to my decision to have an early ASTC vs. waiting until first relapse was Paul's reference to Dr. Polumbo's research from Torino, Italy, showing some benefit for early transplant vs. waiting until first relapse.  I blogged about that visit with Richardson on December 29, 2011:  yesterday-was-very-good-day-at-dfci.  Now, almost two years later, he still refers to that study as being relevant.  That's good news, as there have not yet been any data to contradict that presumption, although clinical trials are still underway to answer that question.  In my mind, the answers may never be definitive, and either choice may be fine.  In any case, I'm happy I made the decision I did, and I certainly can't complain as I am still in remission a year and a half later.

On the issue of consolidation and maintenance therapy, Dr. Richardson strongly recommended at least following a maintenance regimen after a transplant or even after successful initial drug therapy.  While all studies show a Progression Free Survival (PFS) benefit of maintenance (usually Revlimid), some studies don't show any Overall Survival (OS) benefit, which of course is the bottom line.  Paul suggested that the reason is that many studies only continued maintenance for 2 years and then discontinued it.  He reasons that this is a mistake.  A Polumbo study showed OS benefits for maintenance until first relapse.  Paul's take is that 2 years isn't long enough.  Revlimid has a slight risk of inducing a secondary cancer, but that risk is almost always in the first 2 years.  Why take the risk of the secondary cancer without continuing the therapy after the risk is no longer a factor?

Here's the thing. Unlike most cancers, MM is a cytogenetically active disease, where individual patients undergo mutations of the monoclonal proteins over time.  I have blogged about this in the past.  High-risk patients, such as myself, are even more prone to mutations that will create another monoclonal spike, which accounts for our more pessimistic prognoses.  Continuous treatment with an IMID (Immunomodulatory Drug) , such as Revlimid, helps keep these mutated clones under control.  Especially after a stem cell transplant, Revlimid helps the new immune system keep an active eye on these mutations as they occur and keep them at bay. This makes a lot of sense to me.

Some have argued that by continuing to give maintenance therapy over a long period of time, one can become resistant (refractory) and it won't work anymore.  That used to be a big problem when there were few options to replace the resistant drug.  But fortunately that's not the case these days. For example, the IMID Pomalyst has now been approved by the FDA for relapsed MM, which can substitute for Revlimid. Yay!  Now I don't have to worry that if Rev someday stops working, I have no other options.

I am currently on a clinical trial, which involves continuing my Rev maintenance therapy for 3 years.  If I am fortunate enough to still be in remission at the end of that trial, I will have a decision to make about whether to stop treatment all together or continue on some maintenance therapy.  That decision is a long way off, and I hope that all the ongoing research will give me good insight as to what path I should take going forward.  Right now, I just hope that is a decision I get to make.

I have other issues to blog about, including more on the Lyme Disease connection and other potential MM links, but I'll put that off until another day.  I have an appointment with Dr. Richardson on Monday.  I may have something to report about on that.

New Twist on Lyme/MM Connection

I have received a couple of interesting emails lately regarding the connection between MM and autoimmune diseases, including Lyme Disease.  One writer, Kate, has IGA Lambda MM with the t(4;14) translocation, as I have.  While she says she does not have Lyme, she suffers from a variety of symptoms that her doctors say are autoimmune related.  (I wonder if she might actually have a case of undiagnosed Lyme.  Since the tests are so unreliable, there may be no way to know for sure.)  Her oncologist acknowledges an association between autoimmune disorders and MM, but the MM experts don't know what the relationship is yet.  She has also read that IGA MM patients have higher rates of both autoimmune diseases and t(4;14) translocations than other types.  Interesting.  This just adds more fuel to the fire about this type of connection, as far as I'm concerned.

Today I received a fascinating comment on one of my earlier posts about Lyme Disease.  Dee has been treated for Lyme Disease several times, but she feels she had undiagnosed Lyme before that.  She continues to have the usual range of symptoms indicating chronic Lyme.  Fortunately, she is seeing a Lyme-literate doctor.

This year, she was diagnosed with an extremely rare disease:  necrobiotic xanthogranuloma (NXG).  Only about 125 cases a year are reported for this disease, and most of the literature is from Europe, primarily by those in the Lyme Disease community.  However, NXG has been found to have a very high correlation with MM.  She went to an oncologist and found she had elevated monoclonal protein.  After a bone marrow biopsy (BMB),  she was found to have Smoldering Myeloma (SM), and they also found Lyme bacteria Borrelia burgdorferi (Bb) spirochetes in her bone marrow! Wow!

This seems to establish a potential triad between Lyme Disease, NXG, and Multiple Myeloma.  In fact, I found a paper establishing this 3-way link:  http://www.medscape.com/viewarticle/721924_5.  In a retrospective study, 80% of NXG patients showed monoclonal gammopathies.  Furthermore, the paper states, "NXG biopsies suggested the presence of Borrelia spirochetes in six of seven samples, implicating spirochetes as a potential trigger for NXG".

Right now, my head hurts trying to assimilate all this information.  While NXG is very rare, this reveals one probable pathway between Lyme Disease and myeloma, showing that the Lyme Bb instigates the NXG, which in turn instigates the monoclonal gammopathy.  This implies cause and effect, not merely correlation.  Bb is an extremely complicated and resourceful bacterium. It has many deleterious effects on the human body (as I myself have discovered), but I remain convinced that one of the more pernicious effects is that Lyme Disease is a potential trigger for monoclonal gammopathies, including MGUS, SM, and MM.  I'm sure I will be blogging about this more as I gather more information on this topic.

Tomorrow I am headed up to the family farm in Champlain, NY for a relaxing weekend with my son, Jeff, and good friend, Bobby.  Since we don't have good wireless connections there, I may miss a good blog talk radio show tomorrow night at 6:00 featuring Dr. Paul Richardson.  Here is the link:  http://www.blogtalkradio.com/dr-paul-richardson-discusses-myeloma.  The topic is To Transplant or Not To Transplant: Thats the Question.  Fellow blogger Pat Killingsworth is one of the panelists.  I already know Paul's view on this, as we have discussed it at length.  However, it is a hot topic of conversation these days in the MM community.  Several clinical trials are underway to help answer this question (including the one I am on), so it will be interesting to see if there are any new developments on this topic.  If I miss it, I hope someone will fill me in on it, or I can view it later.

DVT Risk

One of the side effects of my Revlimid treatment is the risk of a deep vein thrombosis (DVT), which is a blood clot which usually forms in the legs.  Such a clot could break loose and travel to the lungs, causing a pulmonary embolism.  That would not be a good thing.  My friend, Bobby, had one of these a few years ago, and it was pretty serious.  Fortunately, he is now fine.  I have been taking a full dose of aspirin every day since being on Rev to minimize the chance of a DVT.  Every month during my physical exam at the Farber, they check to see if there is any pain or tenderness in my lower legs, which might indicate a potential DVT.

Today in the shower, I noticed that my right lower leg was very sensitive to the touch about 8 inches above the ankle.  Hmmm.  I didn't notice any swelling, warmth, or redness, so I wasn't too concerned.  However, I plan to monitor this very closely.

I went online to see what was published about this, and I found this recent article in the Myeloma Beacon addressing this issue:  blood-clots-multiple-myeloma-thalidomide-revlimid/.  The bottom line is that aspirin has been found not to be that effective in preventing blood clots for these patients.  About 7% of patients who take aspirin on long-term Revlimid therapy still develop blood clots, about the same percentage as those who don't take any blood thinners.  However, those taking heparin or Coumadin fared much better.  Hmmm.  If this gets any worse, I will definitely call Mary at the Farber for advice.  Stay tuned.

Today I had a followup visit for my knee.  Fortunately, the cortisone shot for the osteoarthritis (OA) is still working, so it feels pretty good.  I played 9 holes of golf yesterday walking with my pull cart and had no issues with the knee at all.  I told Frank, the physician's assistant, that I felt about 85% back to normal (not 85% better, as I rambled on about in a previous blog post).  He was pleased, and said most people get about 4-6 months improvement from the cortisone.  The next question is what to do when it wears off.  Another cortisone shot is the most obvious next step, especially if this one lasts a long time.  At some point though, that may not work any more.

One alternative would be knee replacement surgery (gulp!).  I have no intention of going in that direction.  Just look at the surgery scars in the picture.  Fuggetaboutit!  I don't plan on entering any iron-man triathlons, so just getting around without much pain will work just fine for me.

The next step would be injections of hyaluronic acid, which can provide up to 6 months or more of pain relief for OA.  This is sometimes referred to as "motor oil" for the knee, as it replaces the lost joint fluid causing the pain from OA.  This typically requires 3 weekly injections to lubricate the knee joint.  My doctor uses a brand called Orthovisc.  Our good friend, Marilyn, has a similar knee problem to mine, and she has had two injections of a similar brand, Synvisc, over the past four years with great results.  As of now, however, my knee feels OK, so I'll just keep that option in my back pocket.

I have been remiss in setting up a physical therapy (PT) appointment to help rehabilitate my knee, so today I made an appointment for early November.  I hope to go to a couple of sessions to find out what exercises will help the most, and then perhaps continue them at home or at the gym.  We'll see.

  

Farber, Knee, and LLS

After several weeks of relative quietude on the blogging front, I have more topics to cover today.  This morning I had my monthly Farber appointment.  I hadn't bothered to look at the schedule in detail--I just knew I had to be there at 10:15.  When I got there and finally checked the appointments, I found there was good news and bad news.  The good news was that I was scheduled to meet with Dr. Richardson!  The bad news was that I was scheduled to meet with Dr. Richardson!  The good part was that I haven't seen him since May, and I was delighted to have the opportunity to talk to him again directly about my situation.  The bad part was that I knew it was going to be a long day.

While I was waiting, I met with Muriel.  My numbers this month were great!  The pathology results from last month confirmed no monoclonal gammopathy again, meaning I'm still in remission.  The bilirubin, which I was concerned about last month, dropped from 1.7 to 1.0, back in the normal range.  Muriel said that a number of patients on Rev maintenance have had similar random jumps in bilirubin with no apparent cause.  While a high bilirubin can be indicative of liver problems, none of my other liver indicators are out of line, so it may just be a spurious side effect of the Revlimid.  (Phew!  I'll drink to that.)  My neutrophil count continues to be great at 2.45, well into the normal range, despite the fact that I am taking Rev every day.  Almost everything else was in the normal range.  The only negatives were my HCT and Hgb counts, which have both dropped somewhat, which means my anemia is not getting any better.  That may explain why I still need 9-10 hours of sleep every night, and I still often nap during the day.  You know what?  It's a small price to pay for how good I've been feeling.

By the way, my knee still feels great!  I totally forgot to bring in the CDs with my Xrays and MRIs.  Damn!  Anyway, Muriel said that it was no big deal, because it won't affect any of my treatments at the Farber.  They just want them for complete records, so hopefully, I'll remember to bring them next time.  (Siri, remind me!)  However, she did strongly suggest that I take advantage of the PT prescription I got from the ortho doc.  It can only help, and after the cortisone wears off, it would be good to have built up some of the surrounding muscle.  I can't say I disagree, so maybe I'll try it out for a session or two, and maybe I can continue to do the appropriate exercises at the gym on my own. 

I'm glad I brought my computer and Kindle, so I was able to surf the Net and read while waiting for Dr. Richardson.  He finally arrived at 1:50, two hours and 50 minutes behind schedule.  I was thinking that might have set a new record for promptness, but not so.  I checked my records, but in May he was only two hours and 40 minutes behind.  It was definitely worth the wait though, as it always is. 

After his examination, Dr. Richardson's overall assessment is that I am doing great!  He also thinks that I am looking really good.  It's nice to hear these words from him, because in the past he has been very blunt when he thinks otherwise.  I left the meeting with him feeling super!  Have I ever mentioned that I am really grateful that he is my doctor?

While waiting for Richardson, I perused the DFCI internal publication, "Inside the Institute", which had an interesting article about a $6 million grant from the Leukemia and Lymphoma Society (LLS) to Dr. Irene Ghobrial, one of Richardson's colleagues, to study the biology of clonal evolution of MM to help develop drugs to prevent the progress of the malignancies.  The objective is to help find ways to prevent the progression of precursor conditions (such as MGUS and Smoldering Myeloma) to full blown MM, by finding why MM cells attack the bone marrow and what factors instigate the clonal mutations causing the malignancies.  If such an approach could successfully stymie progression from precursor MM to active MM, perhaps the same approach could also help prevent those in remission from relapsing.  I don't know, but it occurs to me that it would be a reasonable possibility.  I'm excited by this research direction, and from all I have read so far about this, I feel that in addition to the powerful new drugs becoming available, treating clonal mutation abnormalities at the molecular level will eventually lead to individualized treatment regimens and potentially a cure for MM.

I brought this subject up with Dr. Richardson, and he acknowledged that the entire Farber team is involved in this research, and it is a very promising endeavor.  Let's just hope!

Overdue Update

One of my loyal readers emailed me yesterday saying she misses seeing frequent updates to my blog, which was a nice way of telling me to get off my lazy ass and start writing.  Guilty as charged!  I don't why I took this little vacation.  It's not that I'm so busy that I can't fit writing this blog into my crammed schedule of meetings and social events.  As a matter of fact, as I look over my calendar, it is nearly blank, sad to say.  No, just a little laziness and procrastination.  Over the years, I have elevated the process of procrastinating to a fine art, sometimes to my chagrin.  In any case, I'm back.

When we last left the saga of my thrilling adventures, I had just left the orthopedic doctor's office with a shot of cortisone in my right knee.  Wow!  That's pretty good stuff.  My knee immediately felt better, and it still does.  I can now walk and negotiate stairs with minimal pain.  I even walked a 9-hole golf course a few days ago with no discernible aftereffects.  It's still not perfect, but it's "100% better", as they say.

Now that I think of it, I'm not sure what 100% better is supposed to mean.  Better than what?  For example, if I started out only 5% good and got 100% better, I would still only be 10% good, right?  Conversely, if I started out 90% good, I'd only have to get better by 11.1% to be perfect again.  Maybe I just have an odd way of looking at things. Anyway, I digress.

By the way, a cortisone shot in the knee is no walk in the park.  However, on a relative scale, it sure beats the shit out a bone marrow biopsy.  I'm not sure how long this cortisone shot will last.  The physicians assistant said it could last anywhere from 3 weeks to 3 years.  Typically, I guess 6 months would be a reasonable expectation.  After that, I don't know what might come next.  In the mean time, I'll try not to do anything too strenuous with it.

I'm feeling really good, although I still sleep more than I used to.  I've pretty much adjusted to that.  Yesterday I got my flu shot and next Monday, I go back to the Farber for another monthly checkup and Zometa infusion.  That will begin the 15th month of my clinical trial maintenance therapy with the 5 mg of Revlimid daily.  If I can stay in remission for another 22 months, then I can go off the Rev completely, and maybe the Zometa as well.  I'm looking forward to that.  I'm very upbeat about how everything has gone so far.  In fact, as a testament to my optimism, I just took the plunge and renewed my AARP membership for another 5 years! 

The writing seminar at the Farber has started up again for the fall.  Unfortunately, I missed the September workshop because of my knee appointment.  I hope to be able to attend the October one on the 28th.  I could use a shot in the arm to bolster my inspiration to keep writing..

 

Knee Problems

In my last post, I mentioned the sudden onset of a problem with my right knee for no reason at all.  So I had X-rays and an MRI done, and last week I got the results.  The good news was that all the ligaments are intact.  The bad news was that almost everything else sucks.

Knee X-ray showing severe arthritis

The findings were that I have maceration and tears in the medial (inner) miniscus that go from back to front, a possible tear in the lateral (outer) miniscus, joint effusion (aka water on the knee), Baker's cyst and a loose cartilage body behind the knee, and severe osteoarthritis in all 3 joints, with the most serious being chondromalacia (similar to runner's knee).  This latter condition is apparent in the attached X-ray picture, which shows that I have almost no cartilage between my knee cap and femur.  Normally, there should be about a centimeter of spacing there.  Now the bones are practically rubbing together.  Creak!

Looking at these findings, I was wondering how I could walk at all!  Shouldn't I be in a wheel chair?  Surprisingly, however, I've been pretty mobile.  I have some pain, mostly going up and down stairs, but especially after walking for a round of golf (I refuse to rent a cart!).  However, the pain has been tolerable, and I haven't bothered to take any pain relievers for it.

I was kind of disappointed that this happened, because I had been harboring secret thoughts about trying to get in shape to run in a 5K event some time next year in a cancer fund raiser for Multiple Myeloma or Dana Farber.  I had started combining walking with jogging on the treadmill at the gym early in the summer, but I kind of dropped out of the gym over the last couple of months.  I was planning to try to get back in shape again once fall rolled around, but ironically, this happened out of the blue, without my putting any stress at all on the knee.  Go figure.

Today I met with my osteopathic surgeon, Dr. Mattheos.  He was great at treating me after I fell off the ladder last year, although it hurt like hell when he yanked my dislocated finger back into place.  Grrrr!  But I have forgiven him for that.  He seemed a little surprised that I wasn't in more pain than I was.  My knee actually feels pretty good, with most of the pain on the inner side where the main meniscus tear is.  He explained that he could do arthroscopic surgery to repair the tear, but that could actually make things worse, which was his way of telling me that my knee is pretty fucked up.  The main problem is my arthritis, and cartilage repair surgery might actually exacerbate that.

The upshot is that he recommended a cortisone shot to reduce the swelling and let the cartilage try to heal naturally.  So that's what I got.  Who knows if that will work, but it feels pretty good right now.  I also got a prescription for some PT, which I may or may not use.  I have a follow-up visit in 4 weeks to see how it's progressing.  He thinks it is possible that I could get back to normal activity.  Who knows?  There might be a 5K run in my future yet.  But I don't think I will try running anytime soon.

One of Those Days

Today is one of those days.

Last week I suddenly had a pain in my right knee while just walking around the house, so I went to the doctor.  He sent me to have an x-ray and MRI, which I went to the local hospital for on Tuesday.  In the meantime, I have been hobbling around with a knee bandage for the last week.  I played 9 holes of golf yesterday walking (I'm too proud and cheap to take a cart), so the knee didn't feel so good today.  This morning,  my doctor's office called to report that I have a cartilage tear in my miniscus.  Great!  So I have scheduled an appointment with an orthopedic surgeon to see what happens next.  That started my day.

My meds had run out, so I checked with Express Scripts this morning and was told I couldn't get them until October.  So I called my doctor's office and had an emergency supply sent to the local pharmacy to last me for a while.  When I went to pick them up, I had a flat tire in the parking lot.  While trying to change the tire, the lock nut was on so tight that I broke it trying to get it off.  So I called AAA (not AA), who came about 45 minutes later, and he couldn't get it off either.  So he put enough air in the tire for me to get to the local Midas, where they had to force it off with an air hammer.  By then, I realized that I needed new tires, so they put on the spare and I drove to New Hampshire to buy new tires.  But in my brute strength (yeah right!) to try to force off the lock nut, I had also broken the key to the lock nut, so they had to also forcibly remove and destroy all the other lock nuts before installing my new tires.  No more lock nuts.  If anyone wants to steal my tires, just come and get them!  After about two hours and a thousand dollars later, I was finally back on the road.  That was fun.

When I finally got home about 6:30 after my odyssey adventure to pick up my emergency prescription, Gretchen informed me that they had actually been delivered by Express Scripts last week, but she had put them aside thinking that they were hers.  Oops.  Some days are like this.  Today is one of those days.  You just have to laugh about it.

I have been very lazy about updating this blog.  I should have updated this days ago, but I wasn't feeling very creative.  I went to the Farber on Monday for my monthly checkup, and things are still good.  I didn't want to put up a blog post just saying that everything was still fine.  Yawn.

Anyway, positive changes include my white blood cell count up significantly to 4.7, and my RBC, HCT, and Hgb have all increased, indicating that my anemia is alleviating somewhat.  The only negative number is my bilirubin, which jumped to 1.7 (normal is less than 1.2).  This can be indicative of potential liver problems.  Hmmm.  I wonder if that might have anything to do with the prodigious amount of wine that I consumed during our baccanalian Labor Day weekend bash.  I'm not sure I remember all of it, but we had a great time!  Oh yes, and don't tell Dr. R.

Squirrels

I hate squirrels.  They have bedeviled me for years as we have tried to feed the birds around our houses.  We resorted to various squirrel defenses over the years with limited success.  One of the most fun ones was a bird feeder that had a battery-operated spinner that would throw the squirrels off the feeder when they stepped on it.  It was fun to see them tossed 10 feet or so to the ground, but in the end, they would always win.  You see, squirrels are very persistent, and batteries only last so long.  So we got to see the squirrels happily throw them selves around until the battery died and then gorge themselves at will.  Damn!

At our current house, our bird feeder has a lockout which closes the feeder holes if anything heavy such as a squirrel lands on it, so it seem so work fairly well, although the squirrels don't give up.  My new nemeses are the raccoons, which are much more voracious than the squirrels.  They simply pull the feeder up from our deck railing with their paws and empty it in a single night.  So over the last few years, my emnity has been focused on raccoons rather than squirrels.  I won't go into details about how I have battled these perfidious creatures, but to suffice it to say, I have come to some mild accommodation with the squirrels.

Tonight, as I sat on on our Adirondack chair overlooking the Merrimac River at sunset, I noticed a squirrel under my chair.  Our cat, Sophie, was lying nonchalantly nearby just observing the squirrel.  I saw that it was a baby squirrel, and it kept running back and forth under my chair.  After a while, I looked down at it, and it was just looking up at me.  How cute!  What?  I can't believe what I did next.  I actually put my hand down and petted this cute little creature.  What has come over me?  Am I mad?  It scampered off into the woods then, but I was sitting there thinking, what the f*ck, I hate these things, don't I?  Well, now I don't know what I think.  I think perhaps that age has a way of mellowing one into taking a lot of sharp edges off of some of the strong opinions that one once held.  Not completely however.  I still hate raccoons.

We just came back from a wonderful visit with my college friend, Bob, in Seattle.  I'm still feeling really good, although I'm sleeping a lot.  Next Tuesday, I go in to the Farber for my monthly checkup and Zometa infusion.  I'm keeping my fingers crossed that I will still be in remission.  So far, so good.



 

More Research on MGUS/MM Correlation with Other Diseases

A couple of recent articles have highlighted Lyme disease.  One article appeared on the front page of yesterday's Sunday Globe.  It traces the sad history of one woman who suffered long-term debilitating effects of Lyme disease and was confronted by a medical community which was dismissive and in denial.  Familiar story?  Then today, the CDC announced that the actual incidence of Lyme is about 10 times more prevalent than previously thought.  They now estimate about 300,000 people a year get Lyme.  Of course, the article then goes on to suggest preventive measures to reduce the incidence of tick bites.  That's nice, but what about doing something about the ones who get bit?  No suggestions there.  It makes me want to go into a closet, close the door, and let out an inarticulate scream at the top of my lungs.

My last post generated several responses from MM or MGUS patients who have suffered very similar patterns of previous immune system symptoms that I experienced from my untreated Lyme disease.  It's disturbing to read how dismissive the medical establishment has been of their (and my) plights.  Of course, several anecdotal situations such as these don't constitute evidence that there is a statistical correlation between any of these various autoimmune diseases or infections and myeloma.

I've done a little further online research to uncover any studies that may have addressed this issue.  One of the studies analyzing the association between a number of diseases and MGUS was reported by the respected myeloma specialist, Dr. Vincent Rajkumar of the Mayo Clinic.  The study included a lot of Minnesota MGUS patients.  Here is a YouTube video on this study:  Rajkumar video.  For the most part, his study dismissed most diseases as not being correlated with MGUS.  His conclusion was that any association between certain diseases, such as Rheumatoid Arthritis (RA) and Lupus, was probably incidental.  However, when I accessed the full paper, I noticed that Lyme disease was not one of the specific infections investigated.  This was a little disappointing, especially since Minnesota is one of the hot beds of Lyme disease.

On the other hand, another well-respected myeloma expert, Dr. James Berenson, has a different take on this.  In his short YouTube video, Berenson video, he acknowledges a correlation between the autoimmune disorders RA and Lupus with MGUS.  Jeez, I wish these guys would talk to each other.

The most interesting study that I have come across is a Swedish study that appeared in the journal Blood in December, 2011.  This article concluded that a personal and family history of immune-related conditions increase the risk of plasma cell disorders.  Here is a link to the paper:

http://bloodjournal.hematologylibrary.org/content/118/24/6284.full

In this large population study, they analyzed over 19,000 MM patients and over 5,000 MGUS patients, along with nearly 100,000 control subjects.  They studied the association of a variety immune-related conditions with both MGUS and MM.  They addressed four different categories: 1) personal history of autoimmune disease, 2) family history of autoimmune disease, 3) personal history of infections, and 4) personal history of inflammatory conditions.

For those with personal history of autoimmune disease where the autoantibodies are detectable (such as RA and Lupus), there was significant correlation with  MGUS, but not MM.  (Score one for Berenson!).  For those where the autoantibodies are not detectable (such as hemolytic anemia, polymyalgia rheumatica, and giant cell arteritis), a significantly elevated risk of MM was found.  Interestingly, there was a negative correlation between RA and MM, unlike with MGUS, although the authors noted that other studies have shown either neutral or a positive correlation between RA and MM.

It was found that a family history of autoimmune disease was associated with a significantly increased risk of MGUS, but not MM.

I was particularly interested in the results for those with a personal history of infections.  Overall, infections were associated with a significantly increased risk of both MM and MGUS!  A history of pneumonia, septicemia, herpes zoster (shingles), infectious mononucleosis, sinusitis, meningitis, and myocarditis was associated with a significantly increased risk of MM.  Many more infections were highly associated with MGUS.  One of the highest positive correlations between prior infections and MGUS was Lyme disease!  (Interestingly, and somewhat puzzlingly, they did not observe a strong correlation between Lyme disease and MM.)

In the final category, inflammatory conditions were associated with a significantly increased risk of subsequent MGUS, but not MM.

In the authors' discussion, I found the following passage to be of particular interest:  "...certain infections and inflammatory conditions can trigger the development of MGUS or MM.  Approximately one-half of MGUS patients have clonal plasma cells carrying translocations that involve a locus considered to be of importance for initiation and support of clonal proliferation.   It has previously been proposed that infections could be the trigger event for these translocations and thereby generate clonal proliferation, and our findings support this."  Wow!  Could it be that my t(4;14) translocation was in part triggered by the long-term effect of chronic Lyme disease on my immune system?  It sure seems plausible.

The more I look into this, the more I become convinced that assaults on the immune system from various causes, including chronic Lyme disease, lead to elevated risk of subsequently developing MGUS and/or MM.






 

LInk between Lyme and IgA MM?

I've beaten on this poor horse before, but I don't think it's dead yet.  So I'm going to whack away some more.

I just got a comment from someone with MGUS (Monoclonal Gammopathy of Undetermined Significance) who responded to my previous June 10 post about Lyme Disease:  More on Lyme.  This person suffered from Lyme Disease in 2011, which went untreated for months, until the symptoms became significant.  She (I think it is a she, but I'm not sure, since the post response was anonymous) finally got on some serious antibiotics, which brought the symptoms under control.  But then in 2012, she was diagnosed with IgA MGUS.

This is a familiar story.  It's my story, complete with the IgA diagnosis.  She wonders if there is any connection between Lyme and MGUS/MM, particularly the IgA type.  Hello!  In her comment, she makes a rather serious accusation, and I quote, "one of the oncolog i saw said they know amongst themselves that lyme can trigger mgus but since lyme is so politicized and polarized they all keep their mouths shut while people suffer."  Wow!  I really hope this is not the case, but based on my past experience with the medical community on Lyme, it wouldn't surprise me at all.

As you know from reading my past blog posts, I have been fixated on the possible connection between Lyme Disease and myeloma for a long time.  The commenter asked a pertinent question that I have been asking myself for a while:  "I have wondered whether the assault on my immune triggered the IGA MGUS that I have or whether I had the iga mgus first and the lyme made it express itself when attacked."  I have a gut feeling that contracting Lyme Disease suppresses the immune system to the point that any latent monoclonal gammopathy might be unleashed.  My blog commenter theorizes that it might specifically trigger IgA-type gammopathy.  I don't know.  Maybe so.

I have a favor to ask of those reading my blog.  If any of you have contracted MGUS, SMM or MM, I would appreciate it is you could respond either to my blog or directly to me by email (wfohalloran@gmail.com) whether you have ever previously had Lyme Disease or suffered from undiagnosed Lyme Disease type symptoms prior to your diagnosis.  Please include your type of gammopathy (IgG, IgA, etc.).  This is an informal survey, as I'm trying to determine if there is any discernible pattern that would connect Lyme to MGUS, SMM, or MM.   Any anecdotal stories would be of interest.  I would like to compile some information that might possibly shed some light on this issue.

Thank you in advance for your cooperation.  I promise to keep any information you send me strictly confidential.  What happens in Vegas stays in Vegas!

Chemo Brain

For a number of months now, Gretchen has suggested that I am suffering from Chemo Brain.  Well, what does she know?  Pshaw!  Up until now, I have dismissed her suggestions as being somewhat unwarranted.

However, there have been a number of recent incidents that have set me to wondering.  Maybe I do have Chemo Brain.  Chemo Brain is a descriptor covering a broad collection of symptoms of those who have undergone chemotherapy, such as myself.  They usually involve memory loss, difficulty concentrating, difficulty multitasking, being disorganized, etc.

Something happened today that could be a symptom.  We have an electric Sunsetter awning over our deck that protects us from both sun and rain.  It was one of the first things we got when we bought our house about 10 years ago, and it has been a wonderful asset.  We use it almost constantly.  Well, today it stopped working.  Hmmm.  This has happened before, so I was pretty sure about the cause.  Any outdoor outlet must be GFCI protected.  However, the outlet on the deck is not a GFCI outlet, but I was 100% sure that this outlet was coupled with the GFCI outlet in the upstairs bathroom.  I checked that outlet and found it wasn't working properly, as I couldn't test or reset it.  Aha!  So I went to the hardware store and got a new GFCI outlet for the bathroom, confident that this would solve the problem.

I won't go into the details of my installation process.  Needless to say, I decided not to spend a half hour or so trying to run repeatedly from the basement to the second floor to find what circuit breaker the outlet was on, so I decided to do it while it was live.  For the most part it worked fine, although I did get a jolt once (ouch!).  Anyway, I got the new GFCI outlet installed.  Problem solved, right? NOT!

OK, now what?  I scratched my head for a while, checked wiring in the basement, rewired the outlet on the deck, all with no results.  I was crestfallen.  (I want you to take a minute to think about how I must have looked and felt in my crestfallen state.)  I mean it's really important to us that this awning works.  We had to leave the house because a potential buyer was coming to see it.  Just before leaving, I went into the downstairs half bath and noticed that the GFCI outlet that I had recently installed there had been tripped and the light was on.  Could this be the problem?  I reset the outlet and went out to check the awning.  Voila!  It worked!  All's well that ends well, right?

Maybe not.  Now my brain is very confused.  I was absolutely sure that the GFCI outlet controlling the awning was in the upstairs bath.  How could I be so wrong?  This is very disturbing to me.  When one thing that I am absolutely sure of turns out to be wrong, what about all the other things that I think I am sure of?  I think I am sure that I cooked pork chops for dinner last night, but maybe we actually went out and had a pizza.  How am I to really know?  There seems to be a blurring between memory and reality that is hard to fathom.

This is only one instance.  Gretchen has been telling me recently about things she says I have said that I have no memory of saying.  My first impulse is to deny having said whatever it was (unless it was something quite brilliant, which never happens).  But maybe she's right.  Maybe my memory is getting a bit foggy.  Shit!  Maybe I need to record all my conversations to be able to keep the record straight.  That would really suck though.  I don't ever want to have to go there.  A journal maybe?  I don't know.

And another thing.  I usually tend to be rather controlled and am seldom clumsy, unlike Gretchen, who often drops or breaks things.  Until recently, that is.  A few days ago, I knocked an empty glass off our counter and it smashed on the floor.  OK, that's one.  The next day at a restaurant in Newburyport, I knocked over my wine glass, spilling it spectacularly all over myself, the floor, and diners at the next table.  Really cool.  That's two.  Then today, I kicked over another glass and broke it.  That's three.  WTF?  I now consider myself a spastic.  Oh yes, and tonight while weeding in the yard, I lost my balance and fell into a rose bush.  (The scratches are healing just fine, thank you.)  I don't know if that couples in with the Chemo Brain, but those are just more disturbing recent symptoms that don't make me too happy.

As you know from my last post, my medical condition continues to be excellent.  All my test results (except anemia) are great.  However, there appear to be some mental (and perhaps physical) deficiencies that I have to deal with.  With Gretchen's brain damage from her accident, she also has lingering deficiencies to deal with.  Hopefully, we can help each other through these times, and it will all work out for the best for both of us.  Let's hope.

One Year on Maintenance

My Farber appointment this month was Monday, which marked a full year on this Clinical Trial using maintenance therapy with Revlimid.  The news continues to be positive, as my latest SPEP pathology results continue to show no M-spike or monoclonal gammopathy.  It also shows a dramatic jump into the normal range for my immunoglobulins IgM, IgG and IgA.  I wouldn't be too upset if the IgA slowed down a little bit, since that is the one that went cuckoo and caused my MM.  It's currently at 263, which is OK.  When I was diagnosed with MM, it was over 3,000.  As long as it stays under 400 (normal range), I'll be comforted.

Furthermore some of my other blood test numbers have also shown improvement.  Two big improvements are my white blood cell count (WBC), which jumped to 4.2 (normal range) after hovering around 2.9 for the last year, and my absolute neutrophil count (ANC), which jumped from 1.36 to 2.19, which is in the normal range for the first time in a year!  Woohoo!  Mary and Muriel told me that these results show that I am continuing to show a good recovery from my ASCT.

All of this is really good news.  The only turds in the punch bowl are my RBC, HCT and Hgb readings, which continue to show that I am still anemic.  I don't know when or if that will improve, but I have been told that that is a very slow process, and it might be hindered somewhat by my continued use of Revlimid.  You know what?  If that's the only thing I have to complain about, well shut me up!

Last week I had the pleasure of sailing with my good friend, Lew, for a couple of days out of South Dartmouth, MA.  He has a 35-foot Cape Dory sailboat, and we sailed to Vineyard Haven on Martha's Vineyard the first day.  We had good winds and we passed through Woods Hole without incident.  The weather was perfect!  We had dinner on the water at a nice restaurant, and we slept on the boat comfortably.

The next day we sailed to Cuttyhunk Harbor.   As we have done in the past, we bought some fresh swordfish and grilled it on the boat.  It was delicious.  What a treat!  Afterwards, we enjoyed this view of the sunset.  It doesn't get any better than this!  We got another good night's sleep on the boat before sailing back to home base at Padanaram Harbor.  Wow!  What a great vacation!

I have to thank my lucky stars every day that I can continue to enjoy life's adventures such as this one.  If and when a relapse of my MM happens and I can no longer enjoy doing such things, at least I will have memories such as this to comfort me.

More on Celgene and Richardson

Today's Boston Globe has an interesting article about Celgene investing $100 million into the Boston-based biotech start-up, Acetylon Pharmaceuticals.  Drs. Ken Anderson and James Bradner from the Farber are co-founders of the company.

I've blogged about James Bradner before.  He starred in a YouTube video last year espousing the benefits of the small molecule, JQ1:  jq1: miracle molecule.  The video was quite inspiring.  While JQ1 hasn't shown any promise yet against MM, it now seems to be a promising candidate for a male contraceptive and an anti-HIV drug.  Who knew?  Anyway, Acetylon's leading drug candidate is an anti-myeloma drug ACY-1215, which also goes by the moniker rocilinostat. 

Rocilinostat, which is among the class of anti-myeloma drugs known as histone deacetylase (HDAC) inhibitors, has undergone promising Phase I clinical trials.  Other HDAC inhibitors currently in clinical trials include Zolinza (vorinostat) and panobinostat.  ACY-1215 differs from the others in that it is more selective in its HDAC targets (it specifically targets HDAC6).  So far, it has shown good preliminary results with fewer side effects than the other broader-based HDAC inhibitors.

Future trials will involve combination therapies, including Celgene's Revlimid, Velcade, and dexamethasone, to extract the maximum synergistic benefits of the combinations.   It is research like this and ongoing clinical trials like these that give enormous hope to us MM patients that a breakthrough to a cure of this disease may not be far off.

Of course, this is only a small subset of the research into MM treatments.  I've written about the promise of monoclonal antibodies as another means of attack against MM.  And there are other lines of research as well.  If you throw enough darts at a dart board, one of them will finally hit the bulls eye.  From my own experience with darts, it takes a lot of them, but hey, who knows when the magic cure will be found?  I have a sneaking suspicion that when and if that happens, Dana-Farber will be heavily involved.

Yesterday, Pat Killingsworth blogged about the great research team at Dana-Farber.  He referred to a recent article that appeared on the Dana-Farber blog:  new-therapies-bring-progress-against-multiple-myeloma/.  As Pat wrote about this team, "Ken Anderson and Paul Richardson are two of the most renowned myeloma specialists in the world.  If they made sets of baseball cards featuring myeloma docs instead, their cards would be most sought after; like Micky Mantle and Willie Mays!".

In  response to one of the comments on Pat's post yesterday about Richardson, Pat replied, "He is one of the smartest, most creative and caring myeloma docs I know…"  Amen!  Dr. Richardson is all of that.  He is an amazing human being.  I have to keep pinching myself to make sure that I really am lucky enough to have him as my doctor. 

I guess I've gotten a bit complacent about my status.  I'm embarrassed to admit that I forgot to note that July 13 was the 2-year anniversary of my initial meeting with Dr. Richardson when he diagnosed me with MM.  How could I have let that milestone slip by unnoticed without so much as a how-do-you-do?  I know that one of these days I'm going to have to face the reality of a relapse.  That will certainly be a slap in the face to wake me up.  In the meantime...party on!

Celgene/Richardson Team

After a whirlwind week traveling to New York and back and then to San Francisco, we are finally back home to decompress.  The Jimmy Fallon show was an awesome experience for us all, especially Jason.  In case you missed the show, here is a YouTube video of the segment:  http://www.youtube.com/watch?v=_6KSKIiDL0o.  Jason was awesome!  He was a really good sport and played it up to the max.  There were some irreverent comments on the YouTube video about Mike and me holding hands with our blindfolds on, but they were nothing compared to the flak I received from my own family.  Gotta love em!

Jason and admirers

After the show, Jason was mobbed by a number of women wanting to get their pictures taken with the new celebrity.  He seemed to enjoy the attention, but Jessica...not so much.  After a few minutes of watching his female admirers fawning over him, she finally announced, "OK, we're outta here!"

All in all, it was a once in a lifetime experience for us all.  Jason will now have to endure the long process of growing his hair back again, but I'm sure it will be worth it.  As he emailed us afterwards, "I wanna jump thru a ten foot poster of myself every time I enter a building!"

Thursday morning we drove back to Boston in time to re-pack and head to the airport to board a plane to San Francisco.  We had a delightful weekend with Holly and Ryan.  Friday, Ryan and I played 18 holes at the Presidio Golf Club trying to prove to each other who was the worse golfer (it was a tie), while Gretchen spent the day at Holly's school.  Some delicious meals, sightseeing, Farmer's Market, a ferry ride to Tiburon, and just hanging together out all made for a wonderful time.

On my last visit to the Farber, I picked up a copy of their house organ "Impact", which has a very interesting article about Celgene and Dr. Richardson.  There has been a lot of discussion over the years about the close ties between big Pharma and the medical establishment, and whether these relationships constitute some sort of conflict of interest.  While there may be instances where such ties work to the disadvantage of patients, this case is certainly not one of them.  Dr. Richardson is on the Advisory Board of Celgene, and has been active in clinical trials with Celgene products, most notably, Revlimid.  It is Richardson's ground-breaking trials that have resulted in the RVD (Revlimid/Velcade/dexamethasone) drug combination that is now the gold standard treatment for treating Multiple Myeloma.  Obviously, this partnership has benefited everyone.

Recently, Celgene's newest MM drug, Pomalyst, received FDA approval, for which Richardson had a leading role.  Specifically, he demonstrated Pomalyst's efficacy in both Phase I and Phase II trials, with the Phase II study providing the basis for accelerated approval.

This article reports that Celgene has just donated a $1.1 million gift to support Dr. Richardson and his team in future clinical trials.  "Celgene's extraordinarily generous support helps make essential early-stage studies possible," said Richardson.  "Results from our studies suggest that our approach is likely to have an enormous impact on our ability to better fight multiple myeloma at its various stages, an so further improve patient outcome."  As Celgene put it, "This makes the work done over the years by Dr. Richardson the leading edge, and Dr. Richardson a powerful force who has been an ideal partner for Celgene."

Hmmm.  Maybe I should buy some stock.

Lyme Disease and Jimmy Fallon

Just as I thought my latest rant on Lyme Disease would calm me down on this topic for a bit, a couple of recent news items have inflamed my passions on this subject once again.

Last Friday, Pamela Weintrab, a CNN contributor, posted an editorial on her fight against Lyme Disease.  Here is the link to her column:  weintraub-lyme-disease.  She recounts the story of her long fight with the medical establishment to get her son properly diagnosed.  After two years after being denied treatment, despite a positive Lyme Disease test, her son "suffered aversion to light, profound fatigue and shooting pains throughout his arms and legs".  Boy is that a familiar story! After being told that her son had a psychiatric problem, it took the next decade struggling for him to get well.

As she points out in her piece, "When doctors attuned to the CDC's rigorous definition resist diagnosing any but the most classic patients -- those with an obvious Lyme rash or highly positive test -- it means patients are left to advance to later, harder-to-treat stages of the disease".  She also states that "standard tests based on legacy technology pick up real patients between just 45% and 75% of the time".  Therefore, anywhere from 25% to 55% of of patients with real Lyme Disease get a false negative on the test and may therefore go untreated.  This is an outrage!  She summarizes with the thought that those deniers in the medical establishment are "circling the wagons around outdated studies, leaving patients desperate and sick while protecting their academic turf".

Then yesterday, the Boston Globe had a front page story on Lyme Disease.  The article was generally critical of the medical establishment's lack of focus on this burgeoning epidemic.  I found the following statistics interesting:  Massachusetts spends more than $10 million on preventing mosquito-borne diseases, and only a few tens of thousands of dollars on tick-disease education.  Last year, there were 33 cases of West Nile virus and 7 cases of Eastern Equine Encephalitis in the state.  That's a spending level of about $250,000 per case of mosquito-borne disease!

However, there were more than 5,000 confirmed cases of Lyme Disease, although the actual cases are believed to be 5 to 10 times greater than reported, because so many patients go undiagnosed or do not fit the stringent reporting criteria. So the state spends about $1 per Lyme Disease case.  Let me ask you:  Are mosquitoes 250,000 times more dangerous than ticks?  I'm just going to let that question hang out there for you all to ponder.  WTF?

Jessica and Jason

Last week, our son, Jason, and his girl friend, Jessica, went to the taping of the Jimmy Fallon show in New York.  Jessica got chosen to do an on-stage skit for part of the show, which was cool. We recorded the show and watched it the next day.  However, after the show, Jason got chosen to come back this Wednesday for a special hair makeover segment.  As you can see from this recent picture, he has quite a head of hair to work with.  He has invited Jess, Gretchen and me to appear on the show with him.  We will be interviewed ahead of time, and then come back on stage after the do-over for the "reveal".  This should be very interesting!  The show will air tomorrow night at 12:30 am.  We are driving down to New York today.  After the taping tomorrow, we will rush back in time to turn around and head to San Francisco for the weekend to visit Holly and Ryan.  This business of being retired can certainly get kind of hectic!

Farber Update

Here is one of the pictures of us racing the yacht Dreamcatcher at Block Island Race Week (I'm the geek in the canary yellow).  Jeff, as usual, is crouched over a winch ready to trim the jib, an exhausting job fit only for the young, especially in heavy weather.  I don't think we old farts could have handled it.  It was a chilly day and we were waiting for the rain, which fortunately never materialized.  Despite my not feeling 100% most of that week, I had a great time! 

After not feeling so well a week ago, I have been doing a lot better since.  I feel like I have completely recovered, except I am still more tired than usual.  My blood test results last week were pretty good, except for an exceptionally high reading for alkaline phosphatase, which could indicate either bone or liver problems.  Dr. Guidi wanted to make sure that I got that retested this week.

Yesterday was my monthly visit to the Farber, and I was pleased to discover that all my blood test results had either returned to normal or to my "normally abnormal" range.  My alkaline phosphatase level was back to normal, which was somewhat puzzling.  My nurse, Mary, opined that the previous elevated count may have been caused by some sort of viral infection.  Whatever...it's OK now.  My absolute neutrophil count at 1.36 was below previous months, but might have been even lower if I hadn't taken a week's holiday from the Revlimid.  I am now back on my normal schedule of 5 mg per day of Revlimid.  So far, so good.

I read in the Farber newsletter yesterday that clinical trial data show that long-term therapy with Revlimid is very beneficial for older patients with a form of chronic blood cancer.  While this doesn't necessarily relate directly to MM, many blood cancers show some common characteristics, so I take that as an encouraging sign that my long-term maintenance strategy with Rev is probably a good thing.