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Saturday, December 31, 2011

Happy New Year!

Yesterday, I had an appointment with Dr. Treister, my consulting dentist at Brigham and Women's Hospital.  He gave me clearance to go ahead with the bisphosphonate, Zometa, after my recent dental woes.  Everything has healed fine, so there is no reason to delay any longer.  I will let my medical team know so they can at last send in the "Coast Guard" in the fight against MM.

Dr. Treister also convinced me to go ahead with getting a proper (i.e., expensive) crown and bridge for my upper teeth, rather than continue with the interim temporary solution.  The reason for this is that the temporary bridge doesn't seal the edges properly, making tooth decay more likely.  If I am taking Zometa, the last thing I would need is more dental problems (in case you've forgotten, check out my Sept. 19 post on ONJ).

Reflecting on this past year, I have to admit it kind of sucked.  Getting diagnosed with an incurable cancer is a bit of a downer.  On the other hand, I can't really complain too much.  I'm feeling good, my treatment is working beyond expectations, I have the best medical team in the known universe, and I am surrounded by loving and supportive family and friends.  What's so bad about that?  I go into 2012 with a lot of uncertainty, but then doesn't everyone?

So I'm planning to pop a bottle of champagne tonight to celebrate the New Year with the hope of good things to come.  Happy New Year to you all, and please stay healthy!

Thursday, December 29, 2011

Cycly 6 Day 1

Dr. Paba Prada and me
Yesterday was a very good day at DFCI.  For starters, I had been planning for an annual golfing trip in February, but I found out a couple of weeks ago that they had scheduled me for a stem cell collection appointment during that week.  I was pretty bummed, but I emailed Cathy Colson last week to see if the appointment could be rescheduled.  She forward the email to my new transplant nurse, Muriel, who then spoke to Dr. Richardson.  Bottom line:  they have moved my whole schedule around to accommodate the golfing trip.  They all felt it was important for me to have my vacation.  Wow, what a great team this is!  I am psyched!

Brian and Gretchen both came in for the team meeting yesterday.  As you might expect, I had several questions and issues to discuss with Dr. Richardson.  Our meeting went better than I could have expected.  He fully answered all my questions and gave me some additional insights that have really helped my decision process.

One issue that was really bothering me was a view graph that Dr. Anderson presentated at the recent patient symposium. It had the comment that Revlimid doesn't work well as maintenance therapy for patients with my t(4;14) abnormality.  Since the ASCT clinical trial I am deciding on involves Revlimid as a maintenance therapy, I was obviously concerned.  It didn't make sense to me, as Richardson had previously told me that Rev was good for t(4;14).  When I showed him the offending statement, he was visibly taken back.  As good a friend, mentor, and colleague as Dr. Anderson is to him, he had to admit that this is just a mistake.  He probably meant to say thalidomide, not Revlimid. Whew, that's a relief.  I think he plans to have that corrected, as Celgene would not be too pleased to hear about that.

So, since Revlimid is so good for maintenance, could I get it without volunteering for the ASCT trial?  The answer is yes, but it will be provided free as part of the trial.  Under other circumstances, I would have to pay for it.  So that becomes a financial rather than a medical consideration.

We also discussed the issue of continuing the current protocol until I achieve maximum response, rather than rushing into the ASCT clinical trial at the earliest opportunity.  He agreed with that, although he also confirmed the conclusions presented in the MLN9708 trial paper at ASH that all patients so far achieved maximum response after 4 cycles.  This has tempered my expectations that my Cycle 5 results will show that I have moved from nCR to CR.  I will get those results next week.

Because of the schedule change to accommodate my vacation, they have decided to keep me on the MLN trial for an another month and collect my stem cells after Cycle 7 rather than Cycle 6, which will push it to near the end of March.  Assuming I elect to go with the new ASCT trial, I would probably elect to do the transplant immediately, given the likely event that my MLN protocol will have maxed out by then.

I then asked Richardson about the tradeoff between doing early ASCT vs. waiting until first relapse after front-line treatment with the new effective drug protocols.  He said that recent research is favoring the early transplant option and mentioned the results of a poster session presented at the recent ASH meeting.  I somehow missed this in my so-called "extensive research" of the meeting, mainly because I didn't focus on the poster sessions.  However, this is extremely relevant.  Here is a link to the abstract (No. 3069):

In this session, Dr. Antonio Palumbo presented final data from a phase 3 study on the Progression Free Survival (PFS) of melphalan, prednisone, and Revlimid (MPR) versus high-dose melphalan (MEL200) and autologous stem cell transplant in newly diagnosed MM patients.  Here is the conclusion:

PFS was significantly prolonged in the MEL200 group compared to MPR. This benefit was maintained in the subgroup of patients with standard- or high-risk cytogenetic features...This is the first report showing a PFS advantage for ASCT in comparison  with conventional therapies including novel agents.

Note that this study also addresses my high-risk cytogenic situation, and it seems to definitely tilt the scales in favor of the early transplant option.  As of now, this seems to be the best path for me to follow.

By the end of our meeting, Dr. Richardson and I were definitely on the same page.  I feel that I am fully onboard with the treatment options and the various important factors that have to be considered.   He expressed his appreciation for my taking an active interest in my treatment and feels that we have become a good doctor-patient team, which he much prefers to a patient who just asks him what to do.  I continue to be tremendously impressed with Dr. Richardson, and I know how lucky I am to have him as my doctor.  I still have a couple of months before I have to decide on participating in the ASCT clinical trial, but I am clearly leaning in that direction.

Tuesday, December 27, 2011

Decisions, Decisions...

Tomorrow we meet with Dr. Richardson and the rest of my medical team.  The question about my participating in the ASCT clinical trial (BMT CTN 0702) will be front and center.  I have been allowing this issue to fester in the back of my mind for the past several weeks rather than trying to analyze the shit out of it.  Now it's time to, well, start analyzing the shit out of it.

I'm starting with a few assumptions:
  • I should continue with the current MLN9708 protocol as long as I continue to improve each cycle, delaying any transplant until I reach a maximum response (hopefully CR or sCR).
  • I will still be eligible to participate in the ASCT clinical trial after such a delay.
  • Insurance will cover the expenses of collecting my stem cells even if I don't use them immediately.
Aside from the MM, I am in good health right now, in that my liver, kidneys, heart, and lungs are all functioning within or close to their normal ranges.  This is an important consideration for doing a stem cell transplant.  If I delay ASCT until my first relapse (hopefully several years downstream), I will be in my seventies, and who knows what my health level will be then?  As one ages, renal function declines, and frailty, weight loss, and decreased ability to tolerate toxicity become factors.

Normally, enough stem cells are collected to perform two transplants.  If I elect to have a transplant in the near future, I still may be eligible for a second ASCT downstream.  However, if I delay the first one until after relapse, I will likely only be eligible for a single transplant due to age and/or health considerations.  This could take one of my options off the table.  It may be advantageous to have both novel drug regimens and two transplants available to me as therapy choices.

While there is a lot of research underway now to examine the efficacy of delaying ASCT until first relapse, not enough data is available yet to validate this approach.  As I mentioned in a previous post, there are some doctors who feel that until more new and effective drug therapies become available 5 or 10 years from now, the current approach of doing ASCT early is still the best therapy option.

This exercise is to get my thoughts together a bit before meeting with Richardson tomorrow.  In the end, I will most likely follow the course he recommends.  However, I want to be comfortable enough with the various options to have a complete buy in to the path selected.

I am not looking forward to undergoing this ASCT procedure any time soon.  It almost seems contradictory for me to be feeling really good and then make a decision to undergo a risky procedure that will make me feel really bad for a while.  However, at this point I'm thinking that I probably should do this.

Sunday, December 25, 2011


It's Christmas day.  I don't have any medical insights to add to my blog tonight.  I just want to share with you all how wonderful it is to have my family around me now and for the next few days.  And I want to thank you all for your caring and concern for me.  You have boosted my spirits during this time of trial.

A life-threatening disease helps one to focus on the  important things in life.  Of those, family and friends are at the top of the list.  As one gets older, there are fewer mountains left to climb and windmills left to tilt at.  One is left with the hopefully golden memories of the days of yore, as most of mine are, and with the connections and loved ones of the present.  That means you. 

I am feeling healthy, happy, hopeful, content, optimistic, and only slightly anxious for the future, whatever that may bring.  Thank you for being there for me.  It means the world to me.  Have a very Merry Christmas!

Monday, December 19, 2011

DFCI Patient Symposium

Gretchen and I attended the DFCI Patient Symposium on Saturday.  While it was interesting, I didn't find it quite as informative as the first one we attended in September.  Undoubtedly, this is partly due to my having learned a lot since then, as well as my having closely tracked the results of the recent ASH Meeting in San Diego.  Still, it was a worthwhile event.  Anderson and Richardson make a great team, and both of their presentations were excellent.  Dr. Noopur Raje of Mass. General also gave a good presentation on targeting bone disease. The main focus of the symposium was on some of the new drugs being developed.  However, there wasn't much discussion on stem cell transplants, a topic of some current interest to me.

Now that the ASH Meeting is over, I can try to distill what I think of the current state of research in MM.  While there are many exciting drugs under development and lots of clinical trials assessing various treatment options, the fact remains that many of these drugs are years away from coming online.  From a patient's perspective, this is a little frustrating.  The last major MM drug to be approved by the FDA was Revlimid in 2007.  Only two others (carfilzomib and pomalidomide) are likely to be approved over the next couple of years.  In the meantime, one can get access to these new drugs by participating in clinical trials.  Fortunately for me, I am hoping not to need some of these new drugs in the short term, since my therapy is working quite well so far.

As for the transplant question, the jury is still out on the timing.  With the success of the novel-agent drug therapies, trials are underway to determine whether ASCT should be performed early, as is now standard practice, or whether it makes sense to delay until first relapse.  There seems to be consensus on a few points:
  • Be as aggressive as possible in trying to contain the disease up front.  Don't hold anything back in reserve for the next relapse
  • ASCT is most effective either up front or after first relapse.  After that, its effectiveness diminishes
  • Achieving VGPR or CR before undergoing ASCT leads to much greater median  Progression Free Survival (PFS) and Overall Survival (OS) and is a relevant objective for MM treatment
Yesterday, Pat Killingsworth reported in his blog about the IMF journalist workshop he attended while at the ASH meeting:

I found the last part of his blog regarding comments from Dr. Orlowski at that session to be memorable:

"Answering the oft asked question about whether new novel therapies will someday replace auto stem cell transplants, Dr. Orlowski responded with a qualified “yes.”  Dr. Orlowski clearly believes SCTs will become a less important part of myeloma therapy someday.
“And when would that be?” a reporter asked.  “Not until a number of these newer drugs become available in five or ten years.”  he answered."

OK then.  This is somewhat relevant to the decision I must shortly make.  While there is reason to believe that with the successful novel-agent therapy I am now getting, I could decide to defer ASCT until my first relapse, there is still not enough data to validate that it would be the best approach.  Decisions, decisions...

You may have noticed the time tag on this blog.  Yes, it's 4:30 am!  Don't ask me what I'm doing up at this hour.  I have no idea myself.  I can't blame it on the dexamethasone, since I haven't had that since Tuesday.  I just woke up a while ago and decided to get up.  My schedule has been a bit odd lately.  I may go back to bed soon.  Then again, I may not.

Wednesday, December 14, 2011

ASH Meeting Updates

The American Society of Hematology Annual Meeting just concluded in San Diego.  I have been getting dribs and drabs of updates on the oral papers and poster sessions from Pat Killingsworth and the Myeloma Beacon (see Helpful Links).   The paper I was most interested in, of course, was the update on the MLN9708 clinical trial that I am participating in.  Here is an excerpt from Millenium's press release about the results:

– 100 percent of 15 evaluable patients achieved a partial response or better, including four complete responses, five very good partial responses and six partial responses — 14 of 15 achieved partial response or better after cycle 1, 100 percent achieved partial response or better by cycle 2

– No patient has progressed to date

Although it is very early to reach conclusions, these are excellent results, comparable to those achieved by Velcade combination therapy, which is the current standard.  The Myeloma Beacon also reported on this paper presented on Monday, but gave some slightly different numbers (based on only 10 patients):

This article reports that participants in this MLN9708 trial have the option to undergo stem cell transplant after 6 cycles, which is consistent with my current schedule to have stem cells collected after Cycle 6.  Another interesting comment in this article is that all patients in this trial have achieved best response by the 4th cycle.  This is a little disappointing, as I was hoping to achieve CR during the current Cycle 5 (I have been in nCR since Cycle 3 because of my positive immunofixation test).  It appears that this is not likely, based on the trial results to date.  Oh well.  I can still hope.

On Saturday, Gretchen and I will be attending the Patient Symposium at DFCI.  We will get updates of the many exciting results presented at the ASH Meeting.  I'll be paying particular attention to hear their take on timing of stem cell transplants.  In addition to MLN9708, excellent results were reported for carfilzomib, pomalidomide, elotuzumab, bendamustine, and other hard-to-pronounce drugs.  Who comes up with these names?  They don't exactly roll off the tongue.

Today I received a letter from DFCI announcing all the members of my transplant team.  I guess things are quickly moving in that direction without any inputs from me.  Gulp!  I'd better get cracking on doing my research on which path to take going forward.

Yesterday was my DFCI infusion day.  I also attended the writing workshop at noon.  The workshop is very interesting, both because of the people participating and for the subject matter.  Our assignment for yesterday was to "write small" about some object that we use (tool, etc.).  The objective was to concentrate on the small details of the object, ideally getting at bigger ideas through something precise.  Believe it or not, I actually wrote a Shakespearian sonnet about my Craftsman power lawn mower.  I'll let you chew on that for a while.

Thursday, December 8, 2011

To Transplant or Not To Transplant?

I have been giving some thought to the question of whether I should volunteer for the clinical trial that Dr. Richardson recommends to perform an ASCT in the next few months followed by Revlimid consolidation/maintenance, or to continue with the current MLN9708 clinical trial indefinitely.  Based on the limited amount of research I have done to date, I can make a case for either option.  So, here is a debate I am having with myself over the efficacy of these two approaches.

Case for entering the ASCT clinical trial at this time:

Opting to enter the ASCT clinical trial is the only option that makes sense. To do anything else would be really stupid, and here's why. Standard therapy for patients under the age of 70 is to do initial induction therapy followed by ASCT. Studies have shown that patients who received ASCT early have better Overall Survival (OS) than those who received ASCT after relapse (Ref. 1). The most important predictor for a good outcome is to be in Complete Response (CR) at the time of ASCT, resulting in Progression Free Survival (PFS) of 47 months and OS of 91 months (Ref. 2). I am already nearly at CR. If I wait until relapse to do the ASCT, I may not be in as favorable disease status as I am now, and ASCT may not work as well. Furthermore, recent trials have shown that Revlimid is an excellent maintenance therapy after ASCT, trumping even tandem transplants (Ref. 3). Since Revlimid is not FDA approved for this purpose, the only way to get the benefits of Revlimid maintenance is to be a part of this trial. Since I am close to 70 now, my age is another reason to opt for an early transplant.

Case for continuing MLN9708 trial and postpone ASCT until relapse:

Opting to continue with the MLN9708 clinical trial and postpone ASCT until first relapse is the only option that makes sense. To do anything else would be really stupid, and here's why. This MLN9708/Rev/dex trial is doing extremely well, with 100% Overall Response Rate (ORR) to date (Ref. 4), which indicates it may even be a better induction therapy than Velcade/Rev/dex, which is the current gold standard. The fact that I am almost in CR already augers well for a long-term benefit. The planned maintenance therapy is to continue with MLN9708. While this is unproven, Velcade has been shown to be a excellent maintenance therapy drug, and MLN9708, which is similar but more powerful, may work even better. If not, Velcade is always available. Many patients opt for early ASCT for quality-of-life reasons due to peripheral neuropathy (PN) associated with Velcade. I have no such issues, with minimal side effects from my treatment. In fact, ASCT is a serious invasive procedure, requiring weeks of hospitalization and months of restricted activity. Furthermore, there is a 4-5% mortality risk from the procedure itself. Recent research has also shown that with the new induction therapies, delaying ASCT until first relapse won't affect OS (Ref. 5). What about the risk of waiting until after age 70 for ASCT? Not so much. Recent tests (Ref. 1) have shown that patients over 70 without co-morbidities (heart, lung, kidney, liver problems) respond as well to ASCT as younger patients, even with lower levels of the chemotherapy melphalin (140 mg vs. 200 mg) that Richardson said he would use for me. Other than the MM, I'm as healthy as the proverbial horse, so keeping ASCT in reserve until first relapse makes sense. 

OK, readers, what do you think?  Did I make the better argument, or did I?  I welcome your comments.  Not that I plan to make my decision on the basis of a straw poll, mind you.  The only votes that count are mine, Gretchen's, and Dr. Richardson's, not necessarily in that order.  However, I'd like to be knowledgeable enough to be really comfortable with whatever the final decision is.  I plan to continue reading and learning so as to either further confirm or refute some of the arguments above.

Monday, December 5, 2011

Cycle 4 Results

 I've been waiting anxiously all week to find out how the test results came out after finishing Cycle 4 of the MLN9708 protocol.  I got some preliminary results on Saturday from the online Patient Gateway which looked very promising.  I called Kathy Colson today to get the electrophoresis report, which quantifies the M Spike, and the immunofixation report, which detects any trace monoclonal gammopathy.

I was a bit disappointed to find that the report was the same as last month, i.e., no M Spike could be "quantitated" on the electrophoresis, but immunofixation showed that there is still a faint M Spike.  This means that I must still be classified as VGPR rather than CR.  Complete Response requires that the immunofixation test be negative.  Drat!  However, I am still quite happy with the results, because almost all the numbers showed significant improvement over last month.  Here is an update to my test results going back to the start of the clinical trial:
Test Name Reference Range 8/1 8/30 9/27 10/25 11/29

Gamma M Spike 0 g/dL 1.96 0.41 0.13 0 0
IgA 70-400 mg/dL 3180 659 148 80 88
IgG 700-1600 mg/dL 246 248 292 249 312
IgM 40-230 mg/dL <5 9 15 28 24
Kappa/Lambda 0.26-1.65 578 26.7 4.5 3.4 0.7
24hr urine total protein <102 mg/24 hr 392 60 38 47 20
Albumin 3.7-5.3 g/dL 3.5 3.8 3.7 3.8 4
Beta2-microglobulin <2.7 mg/L 3.3 1.9 1.8 2.4 1.7
Red Blood Cell Count 4.2-5.6 M/mcL 3.4 3.7 3.9 3.8 4.1
Hemoglobin 13.2-16.7 g/dL 11 11.3 11.7 11.5 12.2

The most dramatic change is the Kappa/Lambda ratio, which is now in the normal range!   That's a 99.9% drop since August.  This means there are far fewer of those nasty free monoclonal Kappa light chains floating around in there, which has to be good news.  I was also pleased to note that the urine protein levels continue to drop, and both albumin and beta-2 microglobulin are going in the right direction.  My anemia numbers (RBC, Hgb) have also moderated to the best levels since I started, and I notice that I am not feeling as tired as I was.  Despite the existence of trace amounts of M protein, it is clear that I am continuing to respond well to the treatment.  (I'm taking time out here for a couple of Hurrays and Yippees and to jump up and down with my new-found energy.)

Everything I have learned so far about MM treatment indicates that one of the best prognoses for long-term survival is to achieve good response to the initial induction therapy.  For those undergoing stem cell transplant, achieving CR either before or shortly after ASCT offers the best chance for long-term remission.  At the rate I am going, I would hope to achieve CR over the next couple of cycles and continue to deepen the response to the therapy. I would be much more inclined to volunteer for the ASCT clinical trial that Richardson is recommending if I achieve CR in the meantime.  However, I won't feel like rushing into it as long as the MLN9708 continues to work its magic.  I'm not sure how to balance these considerations, but I have time to figure it out.  In the end, I suppose I will do what Dr. Richardson recommends, but we'll see.

Today, Kathy told me that Dr. Richardson has decided not to collect my stem cells until after Cycle 6 of the protocol.  That means it won't happen before late January or February.  That's fine with me.  It gives more time for the current protocol to continue to beat down the MM before collection, and it also gives me more time to decide about whether to enlist in the new ASCT clinical trial.  The only down side to waiting on stem cell collection is that Revlimid reduces the stem cell count, which can make it harder to collect sufficient stem cells if we wait too long.  But Dr. Richardson knows what he's doing, so I'm not worried about this.