So I got my monthly tests back last week and saw that “faint monoclonal lambda light chain” present under IFE. Still nothing under SPEP. But this isn’t noise — it’s not going away on its own.
I need to get to the bottom of this. It’s not like me to sit back and just let this happen without thoroughly understanding it and taking appropriate action. I think I was occupied with the first order question — is this bad? — and then when information was (as with everything with Myeloma) equivocal, I reverted to trusting in BB to see what happens in January. And I do trust BB.
But this isn’t proactive enough for me.
I first took a look more thoroughly at the work that is out there on this topic. The most direct reference is from work done by Mayo, Minnesota, published in 2011. The full article can be found here.
First, secondary MGUS refers to a new monoclonal protein, distinct from the original protein. We will need to determine whether or not the protein I exhibit now under IFE is different from the one I originally presented with. This can be done — hopefully — through a process called immunophenotyping. A bunch of antibody tests are done on the blood to help triangulate it. I have asked BB to have this done when I next visit UAMS in January, although I would like it done sooner. Like, now, basically. I asked BJ (BB’s right arm) to look into this for me last week, but as UAMS is planning for the ASH conference in two weeks it’s probably fallen between the cracks. I will gently prod.
Anyhow, back to the Mayo article.
* They looked at almost 2,000 patients
* 6.6% of these patients had a secondary MGUS
* A good portion of these were in complete remission for the primary Myeloma at the time they developed the secondary MGUS
* Among the population that received a stem-cell transplant (about 25% of these patients — 458 of them) 104, or 22.7%, were identified as having secondary MGUS. Among patients who were followed at least 8 times over two years (248 of this 458) the incidence rose to 36.2%. So of people that transplanted and were monitored regularly, over a third of them exhibited a secondary MGUS.
* It has been hypothesized that secondary MGUS is the result of “recapitulation of early B-cell ontogeny following stem-cell transplant.” I am informed by an online dictionary that ontogeny is the development of an organism. So this is the immune system reasserting itself. Sounds like good news — but it’s just a hypothesis.
* “Overall survival was significantly superior in MM patients who developed secondary MGUS compared with the rest of the cohort — 73 months versus 38 months.” This is plainly good news.
* “The occurrence of a secondary MGUS 6 months after transplant was associated with better OS, median 102 months versus 68 months.” This, too, is good news. Median survival of 9 years.
* In conclusion, “secondary MGUS is a favorable prognostic factor for OS, independent of year of diagnosis, age, stage and renal function.” Again, good news.
HOWEVER…nothing is this simple.
If I look at some of the key citations referenced in this article, there are qualifications.
* The statement right after that conclusion is “this is consistent with findings from other studies.” However, following that citation leads me to Dr. GT, who told me that he needed to know more about the protein before we can breathe easy (this goes back to the need to immunophenotype that protein as noted at the top of this posting).
* We need to look for spontaneous resolution of this secondary MGUS, because the failure of it to do so “may effect OS, but this needs further study.” So I need to monitor those labs. Maybe it will go away. Spontaneous implies without treatment, so there’s that to consider.
And then there are the lingering questions:
* Mayo does single transplantation, without aggressive pre-transplant chemo or consolidation chemo. What do they think — if anything — the implications of secondary MGUS would be for someone who went through Total Therapy? If it’s the immune system rebuilding, then there should be no difference — but if it’s something else, there could be a difference.
* I’ve spoken so far with two doctors about this, other than BB. GT says I should discontinue Velcade as whatever is left is resistant to it, and that he doesn’t know if this protein is bad and needs to learn more first. Dr. PR, a colleague of Dr. KA and a very prominent doctor, says I should resume Velcade and Revlimid (he modified this after I explained my secondary cancer) and had no opinion on the protein. Disconcerting that neither could assuage my concerns, and disconcerting that they had opposite perspectives on resuming Velcade.
* Most disconcerting: BB’s comment that he doesn’t know what this means.
There is more research to be done. Two papers referenced in the Mayo paper are key. The first is from 2010 and published by a group of doctors with whom I’m unfamiliar and its title ends with “…a matter of undetermined significance.” Their attempt at a clever self-referential play on words doesn’t help resolve my unease. The second paper is much older — from 1989. It is likely overtaken by more recent research, but it may be at such a fundamental level that it could be useful. It is titled “Monoclonal and oligoclonal gammopathy after bone marrow transplantation.” We know (and BB is confident) that oligoclonal gammopathy is a positive thing — if monoclonal gammopathy in that same content is a positive thing, it will be helpful. But again — why is BB not seeing this at UAMS, with all his transplant patients?
That’s enough hardcore science for the day.
I’ve requested a phone consult with Dr. VR at Mayo, who was one of the authors of the study. In my limited experience, Mayo doesn’t do phone consults but as this is such a specific question, perhaps they will make an exception.
Onward. I have renewed focus!