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.