The long gaps between posts could be taken as a sign that my life is returning to some semblance of normal, with no worries about mortality or the interpretation of ambiguous medical information. That would be incorrect, as everyone knows here in the Omicron crest: normal is a half-remembered state, ambiguity is everywhere, and we are all working with it in one way or another.
So I have two issues to discuss. One relates to myeloma, and one to COVID
Needless to say, they also relate to one another.
To restate something that I think I have already described, multiple myeloma (MM) is a disease of the very mechanism by which antibodies are produced. Your basic antibody consists of several pieces (immunoglobulins) produced by what are called plasma cells built in the bone marrow. For those of us with MM, some of the plasma cells that produce one of those pieces have abandoned their station and are simply reproducing themselves without restraint. So the whole antibody-production machinery is out of whack.
Treatment for MM consists of attempts to: 1) kill the specific lineage of renegade cells; 2) tamp down antibody production generally; and 3) do a few things that seem to work, even if nobody really knows why.
I've been "treated" in these ways (one of each of the three approaches described above) for 6 years now, so there is plenty of reason to think my immune responses (especially with respect to antibodies) might be less than optimal. On the other hand, the MM is under control and in many respects I might respond just like anybody else with a normal immune system.
All of this is background to a pair of choices that I need to make. One relates to COVID, the other to MM. Let's start with MM. The particular "high risk" form of MM that I have (deletion of chromosome 17p) led to a tandem stem cell transplant (i.e., one transplant followed quickly by another). Clinical trial results indicated that tandem transplants followed by maintenance chemotherapy were the best option, at the time. The chemo options involved choosing one among several proteasome inhibitors (#1 above), a corticosteroid (#2), and one of several immune modulators (#3).
The drugs I've been taking for 5+ years now are Ninlaro (#1), dexamethasone (#2), and Revlimid (#3). During this time, my disease has been essentially invisible and the side effects of the drugs have been mostly minimal. Moreover, this is a completely oral drug regimen, which allows me to travel and not be tied down to an infusion center. So what's the problem?
From an oncology point of view, Ninlaro seems to be an ineffective drug, compared to its competition. Long-term clinical trials comparing Ninlaro to other proteasome inhibitors don't look very impressive. I came upon this discussion following the December meeting of the American Society of Hematology (the big annual blood cancer conference). It's a real downer, and has had me rethinking the whole Ninlaro thing.
But hold that thought, and let's get back to the antibodies: dexamethasone clearly has a negative effect on the whole immune system, and Revlimid--which has been around long enough that it is (thankfully) off-patent now--is still pretty much in the category of "this stuff works but we really don't know how." Neither of these drugs gives me much confidence about mounting an anti-COVID immune response.
So last Summer I got a COVID antibody test, 4 months after being "fully vaccinated" with two Pfizer shots. It was negative. So I went and got a booster, waited two weeks, and got another test--which was very strongly positive. In November, we were visiting with Rosie in Providence and she suddenly lost her senses of taste and smell. She tested positive for COVID, but no one else did. At that point, four months after the booster, it seemed like a good idea to check the antibody level again. Somewhat to my surprise, the test was still strongly positive. (Rosie recovered quickly, and thankfully has full command of her senses once again.)
Now a couple more months have elapsed, Omicron is rampant, and the FDA and CDC have given their blessings to the idea of a fourth shot for people like me with compromised immune systems, though there is little evidence about how useful a fourth shot is. My current thinking is that I'm going to check the antibody levels first and make a decision at least partly on that basis. If I decide to do another shot, I'll test after, as well. For reference, in mid-July, the antibody titer was basically 0 U/ml, two weeks after the booster it was 2141, and in mid-November 891. A "positive" result is anything bigger than 0.8 U/ml, although what level is actually useful for preventing infection or severe disease is not well established, especially since antibodies are only one piece of the immune response. It's probably reasonable to think that the level should be above 100, maybe more like 500 to deal with Omicron.
As for the Ninlaro, it's likely that I would never have started on it in 2016, if we knew then what we know now. However, I only had a partial response to tandem stem cell transplant, and during these years on the Ninlaro-Revlimid-dexamethasone combo the response has gone from partial to complete to no measurable disease. I feel good and the side effects are manageable. Maybe I could just drop the Ninlaro and it would be the same, but at the moment, I'm leaning to keeping everything the way it is until something else happens. The trio of drugs is working, and the stakes seem too high to mess with that, unless there is a good reason.
So much for a rigorous, quantitative approach to "the lab is me." Out here past the intersection of pandemic and cancer it's all extrapolation and guesswork. Here be dragons.
