Myeloma-Lyme Connection? I Say Yes!

Yesterday we were at DFCI for my blood tests and the test that shall not be named.  Actually, the bone marrow biopsy (oops-I just named it) wasn't so bad.  They perform thousands of these at DFCI, so they really know what they are doing and how to minimize the discomfort.  That's not to say that I would volunteer for this on a monthly basis.  No way, Jose.

The biopsy results won't be back for another week or so, and I fervently hope that I haven't gotten any worse since my last biopsy in February.  That would be kind of disappointing considering what I've been through since then.  I fully expect that the flow cytometry results will show some minimum residual disease, since my recent immunofixation results keep showing a trace of Lambda monoclonal paraprotein in my blood.  But that's OK.  I've been told that this is normal and that transplant patients usually show various traces of monoclonal protein after the procedure.  As long as the plasma level in my bone marrow is less than 5%, I will still be in Complete Response (CR).

My blood tests came back pretty good, although my WBC and neutrophils are still somewhat low from the consolidation therapy.  As of now, I am on maintenance therapy consisting of 10 mg/day of Revlimid every day for the next three months.  After that, they may increase my dose to 15 mg/day, depending on how I respond to the 10 mg dose.  I don't have to go back again until Sept. 24, when I will get another blood draw and an infusion of Zometa.  I should be on a monthly schedule of DFCI visits from now on, as long as I stay in remission.

In a previous post, I promised to revisit the issue of whether there is a potential link between Lyme Disease and Multiple Myeloma.  Some of my anecdotal evidence from other patients (including my own experience) indicate some possible connection, but I wanted to find some hard data that might reveal whether there is a statistically significant correlation.  My initial blog post on this subject was a bit fragmented and didn't include the best data sources.  I did a Google search to see what other studies might have been done on this topic, but all I was able to find were some more anecdotal accounts of a possible link.  So I guess the burden is on me to carry the torch here.  By the way, since Lyme Disease is far more prevalent than MM, I assume that Lyme may possibly contribute to the pathogenesis (e.g., causal mechanism) of MM rather than vice versa.

I've now taken a little deeper look into this subject.  Lyme Disease is a fairly recent phenomenon, with the number of cases increasing dramatically over the last fifteen years or so.  If there is some correlation with MM, one would expect that those states or regions that have an unusually high incidence of Lyme Disease might start to show some increase in the incidence of MM over time.  One good source I used is the CDC website that tracks Lyme Disease case and incidence data by state and year:  http://www.cdc.gov/lyme/stats/index.html.  Another good source is the CDC National Program of Cancer Registries (NPCR), which provides age-adjusted myloma statistics:  http://apps.nccd.cdc.gov/uscs/cancersbystateandregion.aspx.  In order to compare MM incidence from one region or state to another, it is necessary to age-adjust the raw incidence data to account for age discrepancies from one area to another.  This is because MM primarily affects the older population.  For the Lyme disease statistics, I could only assume that they were age-independent. 

The good thing about the NPCR data is that they include the 95% confidence intervals for the state-by-state and regional MM data.  I wanted to select a region with a large enough population to provide statistically significant results.  It was therefore convenient for me to select the Northeast US region (New England and Mid Atlantic), consisting of the nine states of Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, Vermont, New Jersey, New York, and Pennsylvania.  The NPCR data conveniently provides average age-adjusted MM incidence for this region and the total US, along with confidence intervals.  I have summarized these data in the table below.  I wasn't able to get exact correspondence for all of the years for comparison, but I don't think that makes a big difference.

It is interesting to note that this 9-state region has about 18% of the US population, but accounted for 75% of the Lyme Disease cases in 2008!  The Lyme Disease incidence for this region was 39 cases/100K population, which is over 4 times the national average of 9.3 cases/100K.  Looking at the MM incidence, the age adjusted incidence for this region for 2008 was 6.0 cases/100K, with a 95% confidence interval of 5.8 to 6.2.  The US total age-adjusted MM incidence for the same year was 5.6 cases/100K, with a 95% confidence interval of 5.5 to 5.6.  I consider these results to be conservative, since a more accurate comparison would be between the 9-state region and the remaining 51-state region, not the US as a whole.  That would only increase the discrepancy from the numbers I am presenting here.

My interpretation of these results is that one can say with more than 95% confidence that there is a higher probability of contracting MM in this 9-state region which has a high incidence of Lyme Disease than in the US as a whole.  To me, this seems to establish a statistically significant basis for concluding that Lyme Disease is a contributor to the pathogenesis of Multiple Myeloma.  There, I've said it! 

Now before any of you start sending my name into the Pulitzer or Nobel Prize nominating committees, just remember that figures don't lie, but liars can figure.  I'm not sure that I have accounted for all possible variables that might influence these results.  There may be other regional variations that I didn't consider that might possibly account for the observed variations.  Someone researchers may have already looked at this and dismissed it for one reason or another.  I'd be curious to know about any studies on this topic that I may have overlooked.  I would also appreciate any comments or suggestions on my analysis approach, methodology, or any glaring errors that I may have made.   Furthermore, I welcome any personal stories of MM patients who may also have a history of Lyme Disease.

State	Population	Lyme cases	Lyme	MM cases	Age-adjusted	MM incidence
	(millions)	2008	Incidence	2011	MM incidence	95% conf.
	2010		(cases/100K)		(cases/100K)	interval
					2008
Connecticut	3.6	2338	64.9	250	5.3
Maine	1.3	780	60.0	110	5.5
Massachusetts	6.6	3960	60.0	440	5.5
New Hampshire	1.3	1211	93.2	90	5.8
Rhode Island	1.1	186	16.9	70	4.9
Vermont	0.6	330	55.0	40	4.7
New Jersey	8.8	3214	36.5	660	6.1
New York	19.4	5741	29.6	1620	6.7
Pennsylvania	12.7	3818	30.1	990	5.5
Regional Totals	55.4	21578	38.9	4270	6.0	5.8-6.2
US Totals	311.6	28921	9.3	20520	5.6	5.5-5.6
% of US totals	17.8%	74.6%		20.8%

Dinner with Michael

Last night, Gretchen and I had the pleasure of meeting fellow MM patient, Michael, and his wife, Wendy, for dinner in Kennebunkport, Maine.  They live on Long Island and both work in the City.  They were finishing up a week's vacation in Maine.  One of the highlights of their trip was running into George and Barbara Bush at lunchtime yesterday.  While that was surely a lot more exciting than meeting us for dinner, we had a pleasant evening nonetheless.  We had a delightful meal on the ocean, and we had good conversation sharing stories of our respective battles with MM.

Michael had been diagnosed with smoldering myeloma about three years ago.  After a surviving a serious, near-fatal bout of meningitis, he was finally diagnosed with full-fledged MM late last year.  At the age of 51, he is too young to have this disease!  It's not fair.

As I have reported before, Michael then started on the same MLN9708 clinical trial that I was on, but unfortunately, he has not been as lucky as I have been.  He is one of the few patients who did not achieve a good response.  He has been on 8 cycles of the MLN9708 (or should I now say ixazomib?), but his M-Spike has been stable for the last 3 cycles.  He is now wrestling with the decision as to whether to continue the current protocol and hope things don't get worse or switch to a new drug combination (cytoxan, Velcade, dex).  He will make his decision soon, and he seems to be leaning toward making the switch.  He and I will continue to stay in touch and I wish him all the luck in bringing his MM under control.  We look forward to meeting with them again, perhaps next time in New York.

We go in to DFCI tomorrow for me to get some tests and to begin my maintenance therapy, which will consist of 10mg of Revlimid daily for the first three months, and then 15 mg/day thereafter.  I found out that they plan to do another bone biopsy tomorrow to see where I am after all this treatment.  That should be tons of fun.  At the very least, I hope the biopsy results will show that the MM has not gotten any worse.

From now on, I may only have to go back into DFCI once a month to have my blood checked and get my IV infusion of the bisphophonate, Zometa.  That will be a nice change!  The plan is to continue the maintenance therapy on this clinical trial for three years or until relapse.  I hope it's the former.

Consolidation Update

This past week, I managed to squeak through the last cycle of my consolidation therapy.  It didn't look too promising on Monday, as my neutrophil count had dropped to 1.1, barely above the minimum to take my Velcade push.  My  WBC was also at a low of 2.3, down from 4.2 the previous week.  I went back in for my final visit on Thursday expecting to have the treatment halted or delayed, as had happened on the previous cycle.  However, my counts rallied somewhat, so I was able to get my last dose of Velcade and continue my daily Revlimid dose of 10 mg.  Tonight is the last night for the Rev, and tomorrow is my last dose of dexamethasone.  Thank goodness for that!

As a side note, Revlimid, as you know, is a very expensive drug.  Fortunately, my stem cell transplant clinical trial has been picking up the cost of the Rev, so I'm not making copayments for it now, as I did before.  However, Celgene really likes to keep track of every pill.  If I have any left over after a given cycle (which I now do, since in Cycle 3 I missed some days and they also dropped my dose from 15 to 10 mg/day), I am supposed to call them and send the remainder back to them.  Given that these pills cost a few hundred dollars each, I have been reluctant to just pack them up and send them back.  Who knows when I might need them, right?  I'm kind of glad that I waited, because last night, I dropped one of these precious pills into the drain of the sink while I was up at the Farm for the weekend, and I could see it floating in the trap down below, just out of reach.  Oops!  Gonzo bonzo!  So tonight, I will raid my excess stash to finish out my final dose for this cycle.  They'll never miss them, right?  They'll have to pry them from my cold, dead fingers, to borrow a phrase.

I'm not quite sure what comes next.  I go in next Monday (August 27) to have some tests done to re-stage my condition prior to embarking on my next phase, which is Revlimid only maintenance therapy.  I don't know whether these tests involve another bone biopsy or not.  If so, I'll just suck it up and go for it.  I am curious to see whether all this treatment has finally eliminated the cancer from my system.  Somehow I doubt it.  My immunofixation results keep coming back every cycle with the same result:  "Monoclonal gammopathy with faint free Lambda paraprotein".  It seems like I just can't quite get rid of this monster, no matter the transplant and all the drugs I've been taking.  It's a bit disappointing (to say the least).

There have been a couple of interesting developments on the MM front recently.  First, my miracle drug, MLN9708, now has an official name.  It will now be called ixazomib.  Like all those other drug names, this one just rolls off the tongue, doesn't it?  I'm not quite sure that it is an improvement.  At least is shows that there is progress with the drug and that the trials must be going pretty well to give it a generic name at this time.  Go ixazomib!

The other news relates to the supposed miracle drug, JQ1.  I blogged about this last November 3:  JQ1, Miracle Molecule?.  There hasn't been much news about it recently, but the latest splash is that this may be the long-sought-for male contraceptive drug!  I read about this discovery recently in the news, but I didn't realize that it was the JQ1 drug they were referring to.  That's nice, but what about the myeloma research?  I'm sure there's lots more money in the male contraceptive market than in the MM market.  Does this mean they will stop funding the MM research?  I hope not, but one has to follow the money, right?

I plan to follow up with a couple of research areas soon.  I will update my findings regarding a potential relationship between MM and Lyme Disease, and I will also keep you updated on the curious disappearance of all clinical research into anti-IL6 drugs for MM.  I'm still scratching my head on this one.  Stay tuned.

MM and Lyme Disease

Before contracting MM, I suffered two bouts of Lyme Disease.  The first time, it took many months for me to finally get a diagnosis from a naturopathic doctor (my medical doctors were clueless).  In the meantime, I suffered multiple symptoms, including aches, shooting pains, chronic fatigue, rashes, night sweats, Bell's Palsy, and you name it.  I finally got on a lengthy regimen of doxycycline, which eventually brought it under control.  I have a lot of opinions about how the medical community deals with (or rather, does not deal with) Lyme disease, but I won't go into that here.  For anyone interested, there is an excellent documentary, Under Our Skin, which covers this topic nicely.

Since contracting MM, I have run across several patients who have also suffered from Lyme disease at some point in the past.  This naturally makes me wonder if there might be a connection.  Could Lyme disease either contribute to or make one more susceptible to Multiple Myeloma?   I thought this might be a fruitful area for me to do a little research, but where to start?

It occurred to me that if there is a correlation between Lyme Disease and MM, then those areas that have a high incidence of Lyme Disease (e.g., Connecticut and Massachusetts) might show an elevated incidence of new MM cases compared to other states.  I started to look into this, and I identified several states that reported unusually high numbers of Lyme Disease cases.  These include Connecticut, Delaware, Massachusetts, New Hampshire, Pennsylvania, and Wisconsin.  The national average incidence of Lyme Disease is about 10 cases per 100,000 population per year.  However, using state Lyme Disease and population data, I computed an average incidence of a whopping 53 cases per 100,000 for these six states in 2009, more than five times the national average!

I had a little more difficulty coming up with the incidence of MM cases by states.  Most of the data I found was many years old, which wouldn't be helpful, since the diagnosis of Lyme Disease has only mushroomed in the past few years.  However, I did find one reference for 2011 published by the Leukemia and Lymphoma Society which "estimated" the number of MM cases by state for 2011.  I'm not sure what went into this "estimate"...I would prefer just the actual data.

In 2011, there were 20,520 newly diagnosed MM cases in the U.S., which works out to an average of about 6.6 cases per 100,000 population.  For my chosen six high-Lyme states, the estimated data for 2011 showed an incidence of 7.2 cases per 100,000.  Hmmm.  Although this is higher than the national average, this isn't exactly a startling discrepancy.  I would have to dust off the cobwebs and go back to my college statistics to determine whether this represents a statistically significant difference.

I'm not quite sure where to go with this next.  This was just a quick web search, not a detailed analytical effort.  In any case, it is a bit of a teaser, so I might keep looking into this further to see if I can unearth anything else.

I obviously have too much free time on my hands.

Consolidation Cycle 4

We're back from our delightful family weekend in Western Pennsylvania for my niece Meghan's wedding.  We had a great time at the wedding, and I was also able to spend time visiting my 94-year-old mother in her assisted living facility.  She has failed noticeably over the past year, so each visit could possibly be the last.  I hadn't seen her since before my stem cell transplant in February, when I finally let her know that I have Multiple Myeloma.  She is the quintessential worrier.  There is nothing that is too trivial for her to worry about.  I have concluded that excessive worrying is not a fatal affliction.  If so, she would have died a long time ago!  Anyway, she took my MM news back then better than I expected, and she was pleased to see that I am doing so well now.  Having already lost one son to cancer, she doesn't need the extra burden of worrying too much about losing another.  At this point, I think the odds look pretty good that I will outlast her. 

Today was the beginning of my 4th and final cycle of the VRD (or RVD) consolidation therapy.  My blood counts looked good, with my WBC at 4.0 and my ANC level at 3.04 K/uL, both up in the normal range.  My Revlimid level has been reduced from 15 to 10 mg/day for this cycle, based on my recent problem with low neutrophil count.  I also received my monthly Zometa infusion to help build up my bones.

My meeting with Dr. Richardson went well.  He is very happy with my progress and continues to think I am looking good (maybe that's because my hair is growing back).   He was very pleased that I have not yet shown any symptoms of peripheral neuropathy from the Velcade.  I will be continuing on the full doses of Velcade and dexamethasone for this last cycle.  I forgot to ask him why my anemia continues to persist through all of this.  I hope to get some wisdom from him on this topic on my next visit. 

In my last post, I mentioned the recent International Myeloma Foundation (IMF) Support Group Leadership Conference held in Dallas on July 28-29, reported on by Pat Killingsworth in one of his recent posts.  I spared you a discussion on that topic then, but I won't spare you now.  At one of the sessions, Dr. Brian Durie, the IMF President and Medical Director, summarized some of the recent research on better understanding of high-risk patients, which will be reported on at the next ASH Conference in Atlanta in December.  Here is a link:  Killingsworth blog on IMF Support Group Conference.

Durie reported that one explanation might be that high-risk patients probably have more “clones” (different types of myeloma cells) than low-risk patients.  So treatment wipes out most of the myeloma, but misses one or more types of clones.  As a patient's treatment progresses, myeloma tends to develop more clones, making the cancer harder to treat.  This happens in all patients, but especially in high-risk patients.  Researchers feel treating early–and throwing every thing they’ve got at myeloma early–has a better chance of wiping out all or most of the myeloma clones, leading to a longer remission and/or potentially a cure.

This is exactly the approach that Dr. Richardson has been advocating and which I am now undergoing.  I have also addressed this topic in some of my previous posts.  It is somewhat gratifying to see that there seems to be an emerging consensus among the researchers that this is the right approach for high-risk patients such as myself.

Speaking of Pat Killingsworth, he just reported that his last test results showed that his M-Spike has disappeared and he is now in remission.  I have been following his progress since his disappointing results from his stem cell transplant last year, and I am very happy for him.  It is always nice to get good news from other fellow MM patients.  It sends a message of hope and encouragement to us all.

MLN9708 is Not for Everyone

As you all know, I have been very fortunate to have had an amazing response to the experimental MM drug, MLN9708, during my clinical trial.  Most patients on this trial have shown similar good results.  I have previously reported that the Overall Response Rate (OR), which includes Partial Response (50% drop in M-Spike) or better, is 98%, which is excellent.

However, that's not true for everyone.  Last December, I met a fellow patient online, Michael from New York, who was following my blog.  He had just been diagnosed with MM and was considering enrolling in the MLN9708 clinical trial for newly-diagnosed patients.  He got an opinion from Dr. Ken Anderson of DFCI, who encouraged him to do it, so he signed up.  We have been keeping track of each other during the intervening months.  Unfortunately, Michael has not been one of the fortunate ones.  His M-Spike level dropped (from 4.8 to 2.8), but not enough to be considered a Partial Response, and it has now stabilized after 7 cycles on the protocol.  His oncologist suggested he switch therapies.

He emailed me last week, looking for my opinion on what to do.  I suggested that he get a second opinion and offered to email Dr. Richardson for his advice.  Dr. Richardson graciously responded immediately, and suggested that perhaps he may need Cytoxan with Velcade and dexamethasone,  and he offered to consult with him.  I forwarded this to Michael.  Since he had already met with Dr. Anderson, he got a second opinion from him, who confirmed that option.  He then met with his oncologist yesterday, who suggested the same therapy, so it seems like all are in agreement.

I have done some research on the Cytoxan, Velcade, dex therapy (known as CyBorD). This is very highly regarded for newly-diagnosed patients and is on the same par with the other standard therapy option of Velcade, Revilimid, dex (VRD), which I am now taking as a consolidation therapy.  I feel really bad that Michael's MLN9708 trial didn't work out for him, but I really hope this next option does the trick.

I feel fortunate to have made contact with some other MM patients along the way, so that we can share our stories.  It's especially nice if we can meet in person.  It was a pleasure to meet with fellow patient Steve while we were in Buffalo last month, and now it looks as if we may get to meet Michael as well.  He will be traveling to Kennebunkport in a few weeks, and we are planning to meet him and his wife for dinner there.

Last night I took my 40 mg of dex for the week, so who knows how much sleep I'll get tonight.  I usually take a nap during the day and go to bed around 10:00, but today I'm full of piss and vinegar, so who knows when I'll  decide to turn in.  Maybe I'll just sit here and add to my blog for the next hour or so, but I know that would be excruciating for you, so I'll stifle my urge.

Friday we are going to Pennsylvania for my niece, Meghan's, wedding.  I'll be seeing my 94-year-old mother for the first time since before my stem cell transplant.  Fortunately, I have some hair back, so my appearance shouldn't be too much of a shock to her.  It will be great to see my brother, Terry, and his wife, Sherry, and my sons, Jeff and Brian (with Pam and Logan), will also be there for the festivities. 

I also have some other things to blog about, such as Pat Killingsworth's recent visit to the IMF Support Group Leadership Conference in Dallas.  There he got some confirmation that the approach Dr. Richardson is taking with me to hit MM with everything we've got as hard as we can up front is a good thing, especially for people with high risk disease, such as t(4;14).  But since I promised to stifle my urge to go on forever, I'll save that for another time.  Good night!