Yellow Roses

Wednesday, May 25, 2016:

My sweeties and I bought a nice bouquet of yellow roses to celebrate my latest treatment results.  In the last four weeks on Pomalyst (pomalidomide)(POM) and Darzalex (daratumumab)(DARA) my IgG has dropped 20% from 807 to 644 mg/dL, and M-spike 25% from 0.8 to 0.6 g/dL.  These numbers are the lowest that I have seen in my 13 years with myeloma.

Not all of that progress comes in the last four weeks, of course.  Here is a chronology of treatments and results since January, 2016:

• Wed Feb 17 First Zometa infusion, serious reaction to something, likely the Zometa (not relevant to these results).  Still on two-MAB trial. 
• Wed Mar 9 Last trial-drug infusion, then next day PET shows myeloma progression, stop trial and start POM immediately, 2 mg daily & 40 mg dexamethasone (DEX) weekly. 
• Thu Mar 24 Myeloma markers tested after 2 weeks on POM/DEX & trial drug, which has a half life of about four weeks.  Numbers down, see chart. 
• Tue Apr 05 After 4 weeks on POM/DEX & trial drug, M-spike down but can't continue trial drug, start DARA next day. 
• Mon Apr 25 After 3 weeks of POM/DEX & DARA plus fading trial drug, markers down significantly. 
• Wed May 25 After 7 weeks of POM/DEX & DARA, IgG and M-spike down to all-time lows.

Currently all of the immunoglobulins that we measure, IgG, IgA, and IgM, are below the bottom of their respective reference ranges and lower than I have ever seen any of them.  Implications?  For sure, my immune system is weaker than normal, but I don't know if it is actually weaker than it was before the POM/DARA regimen began.  I wish that IgA and IgM weren't so low, but perhaps that is the price to be paid for now, because the myeloma tumor burden has been reduced significantly - has to be.

That's the very good part.  I try to visualize the inside of my bones, dark red tubes with those little Y-shaped IgG Kappa immunoglobulins floating around hunting for the errant plasma cells and taking them out one by one.  Yee-ha!  Take that.

Somehow the POM plays an important part in this scenario too.  I haven't figured out how to visualize that, but for now it's enough to imagine that the POM weakens the cancer cells by reducing their fuel supply, or makes them easier to find, or recruits other parts of the immune system to help,
or whatever it is that POM does so well.

What's next?  One more weekly infusion of DARA, and then, as long as the regimen continues to work, every two weeks until September, and every four weeks thereafter "until disease progression," according to the Darzalex prescribing guide.  The worst-case result would be progression of the disease within weeks, and the best result would be a complete response, where immunoglobulin levels actually return to normal and the myeloma cannot be detected except by extraordinary measurement methods.  The most likely result is in between.  Time will tell, and patience is demanded even if patience is in short supply.

Technical thoughts:

For myeloma geeks: Darzalex is a monoclonal antibody which attacks the myeloma cells directly, just as my own antibodies and other immune defenses can attack them, but more effectively.  It is an immunoglobulin of type IgG Kappa, whereas my monoclonal myeloma cells are type IgG Lambda.  How do the measurements of IgG and M-spike distinguish between these two monoclonal antibodies, when I had received an infusion of Darzalex just the day before the test?  In each infusion I receive a 1200-mg dose of monoclonal antibodies.  When that is diluted by about 5 liters (50 dL) of blood (typical for a human body), it comes to 1200/50 = 24 mg/dL, which is a small value compared with the 644 mg/dL of my own (good and bad) IgG.  Check my math please.

However, since the Darzalex has an estimated half life of 18 days and I am getting weekly infusions, my blood contains more than just the most-recent dose, so maybe the correct amount is two or three times as high, perhaps 50 to 75 mg/dL.  That's a guess - the actual math is well above my pay grade.  Even so, the concentration of treatment antibodies is only about 10% of the reported value of IgG, 644 mg/dL.  Dr WG suggested that the technician who reads the M-spike could separate the myeloma from the treatment, but I don't know if that works for the quantitative measurement of IgG.  More to learn.

Personal thoughts:

Ms Wood Duck on our patio

Two grandchildren are visiting this weekend.  One is learning about birds, and watched a mother wood duck go into our new wood duck house to lay an egg.  The other is sitting in Grandma's lap, helping her read books to him, or getting help from Grandpa's in solving puzzles.  Precious moments all around.  When I was diagnosed the common wisdom was 3 to 5 years and out, but here we are 13 years later enjoying grandchildren who weren't even born then.  I feel so lucky that novel medicines like Pomalyst and Darzalex have kept me alive to get to know them, and for them to know their grandpa.