I have always been a huge believer in second opinions; however, one of the most stressful and anxiety-provoking things is when the experts do not agree.  I am then in the position of having to sort through the differ­ences, try to under­stand how they have arrived at different conclusions, and then try to make a deci­sion based on available and usually inade­quate information.

It’s not exactly news to anyone with multiple myeloma that there are a lot of medi­cal decisions to be made during the course of treatment.  It’s also under­stood that even from the time of initial diagnosis, in many situa­tions, the answers are far from clear.

As I have progressed in my treatment and have gone down a road that seems to have fewer and fewer people on it, this problem seems to have become even worse.  The ques­tions have become more compli­cated, and the data to support any answer is much thinner.

I am now 11 months out from my donor (allogeneic) stem cell transplant ^[1].  I relapsed with extramedullary disease ^[2] (myeloma outside the blood and bone marrow) after the transplant but was able to get that under control with radiation and the “CYCLONE” regimen: Kyprolis ^[3] (carfilzomib), cyclo­phos­phamide ^[4] (Cytoxan), thalidomide ^[5] (Thalomid), and dexamethasone ^[6] (Decadron).

I also had a donor lymphocyte infusion ^[7] (DLI, an infusion of more donor cells) one month ago.  The idea be­hind the DLI is to ramp up the new immune system even further to try to generate a larger graft-versus-tumor effect, in which the donor immune cells fight the multiple myeloma.  The risk, of course, is to exacer­bate graft-versus-host disease ^[8] (GVHD) as well; GVHD is a common complication of donor stem cell transplants that occurs when the donor immune cells mistake the host’s cells as foreign and attack them.  It is a deli­cate balancing act.

This is where it gets really tricky.  The question now is how best to control the multiple myeloma, take ad­van­tage of the transplant and DLI to generate the graft-versus-tumor effect, and not be miserable or sick from GVHD.

The short answer is no one really knows the best answer.

There seems to be agreement on a few points.  One is that I continue to have aggressive disease that re­quires continued treatment.  The second is that single-drug therapy is probably not adequate.  The third is that my best hope for some meaningful long-term survival is to be able to take advantage of the graft-versus-tumor effect of my new immune system.  Beyond those points, everything else is less clear.

How soon after DLI should I start therapy?  What drugs will best achieve the delicate balance of controlling the disease and taking advantage of the transplant without suppressing or over activating the new immune system too much?

As I have mentioned before, many of the myeloma drugs have an effect on the new immune system one way or the other.  Velcade ^[9] (bortezomib) and by inference Kyprolis have been shown to suppress GVHD.  Thalido­mide has also been shown to suppress GVHD.  Paradoxically, Revlimid ^[10] (lenalidomide), while a cousin of thalidomide, is known to ramp up GVHD.  While Revlimid’s effect on the immune system can be used to an advantage to increase the graft-versus-tumor effect, there is significant risk of exacerbating serious GVHD.  And it’s not know whether using Kyprolis will dampen the graft-versus-tumor effect.

There really aren’t enough people in my specific situation to have any meaningful studies to answer the questions about which treatments to use and when.  Doctors are forced to rely on what is known of the basic science, anecdotal experience, and finally and sometimes most importantly, gut feelings.

I get all this.  Of course I don’t want to do anything stupid, but at this point I am more than willing to take some chances and to try some things outside of the box.  Somehow I don’t think that playing it safe is the answer right now.

We are planning with some trepidation to use Kyprolis starting two weeks after DLI and add Revlimid begin­ning four to six weeks after DLI.  This might work, it might be a disaster.  We can always change course in midstream if need be.

I know to some extent I’m a guinea pig.  I accept that.  I don’t think there is a lot of choice.  The good news is that it seems like there are options.