More research on the new protein

As I suspected, Mayo was not willing to let me have a phone conversation about this particular topic.  So rather than contemplate flying to Rochester, MN in winter for what will amount to a 10 minute conversation, I’m going to see if BB will be kind enough to arrange a scheduled call with Dr. K or Dr. VR when I next visit UAMS, if not sooner.   My local guy could also call one of them — but I’m sorry to say I’m not sure they would take his call, as busy as they are.

In the meantime, I’ve done more digging.

The prevailing wisdom as of 2006 — as agreed upon by a host of doctors, including BB, VR and several others with whom I have consulted (GT, KA, PR) or mentioned here — was that any return of protein under immunofixation constitutes disease relapse.  That would be bad.

In 2008, however, this study, published in the British Journal of Haematology, noted that people with a “high degree of response” to therapy exhibit “atypical serum immunofixation patterns.”  They go on to say that this is “not associated with new clonal plasma cells or other lymphoproliferative processes, and molecular remissions were documented.”  Molecular remission is no longer the state of the art but it does mean that people in complete remission can exhibit monoclonal proteins under IFE.  In fact, in their study of 72 patients, these patterns were seen in 71% of those who achieved complete remission under their protocol, versus in 23% of people that did not, and they were seen in 100% of those who exhibited some response to therapy.  Now these include those with oligoclonal protein, which I had as well — not everybody had monoclonal secondary MGUS.  This study is one of the ones referenced by the Mayo paper yeterday.  The other is quite old, and didn’t have much to add.

In this British study, they had a couple of observations.  The first is that while they used to see this in post-transplant patients, they now see it in people that DIDN’T have a transplant as well.  They take that as a sign that novel drugs alone are able to achieve the same depth of response as transplants, and they anticipate seeing more of these proteins as therapies are more effective.

The second piece of information is rather interesting.  Their hypothesis on what causes it is roughly as follows:

* The spectrum of proteins in our immune system is like a cup of water that must always remain full.  The cup itself may get larger or smaller (consider this the total protein number) but regardless of the size of the cup, it must be full of water (the individual proteins).

* With myeloma, the monoclonal protein crowds out the normal protein and results in a non-functioning immune system.  As M protein goes up, it displaces the regular part of the immune system.

* When the myeloma is beaten down, the immune system gradually returns in order to fill the cup back up.

* If the myeloma is treated particularly well, there is so much myeloma gone before the immune system can fill the glass back up properly that the water that’s in the cup looks around and says “oh crap, we better make more of ourselves” but that results in some non-cancerous duplication since there isn’t enough “original” water to keep the cup full.

The more medically correct (and jargon-filled) version of this is as follows:

Recent reports demonstrate that in normal bone marrow, there is a plasma cell compartment that has a capped, or finite, population of cells. In order for new, normal, plasma cells to occupy this bone marrow niche after antigenic stimulation, older plasma cells must be replaced (Odendahl et al., 2005;Radbruch et al., 2006). It may be possible that BiRD therapy (or high-dose chemotherapy) clears the bone marrow of malignant plasma cells in such a rapid and complete manner that an environment is created that allows benign plasma cells to expand within the predefined niche without competition. Certainly, the wide spectrum and variability of the ASIP protein isotypes, the recent confirmation that normal plasma cells express the inhibitory FcγRIIb receptor which suppresses normal polyclonal Ig expression, and the finding that administration of tetanus toxoid vaccine after stem cell transplantation induces oligoclonal banding patterns, all support the theory of rapid oligoclonal plasma cell expansion after the clearance MM cells as a potential cause for ASIP generation (Gerritsen et al., 1994; Xiang et al., 2007).

Once again, though, what’s important is to be sure that the new protein is NOT the same as the original protein.  So I’m back where I started, kinda: if this is the old protein, I’m in deep doo-doo.  If it’s a new protein, it’s probably consistent with profound remission or cure.

I *must* get that blood immunophenotyped.