Patient #1: Is PD-1 the answer?

So now that we are underway with Plan B, it would probably be a good idea to give some more details on what exactly Plan B is and how it’s going to help me overcome this pesky melanoma nuisance.  As the last blog post read, we started last Friday with the Merck PD-1 trial at Holy Cross Hospital here in Fort Lauderdale.

What is PD-1?  PD-1 stands for Programmed Death-1 – nice, fellas, we couldn’t have picked something a little softer, just in case it was ever critical in treating cancer?   Although commonly referred to as “PD-1”, the syntactically correct description of the infusion I am receiving is a “PD-1 antibody” or “anti-PD-1”.  PD-1 is a protein found on the surface of T-cells (immune system cells) in our bodies; this protein binds with protein PD-L1 that is expressed in cancer cells, and together they protect the cancer cell from attack by our own immune system. Basically, we have an intruder in the midst and a turncoat in our army of immune cells that enables him to remain hidden.

Anti-PD-1 is an immunotherapy drug that targets breaking that PD-1/PD-L1 shield so the loyal soldiers can get in there and give these tumor cells a good old-fashioned beating – kind of like the whupping those responsible for the Boston Marathon tragedy yesterday are going to get.  The antibody primarily prevents the binding of the PD-1 and PD-L1 proteins; I can’t fully articulate the biology behind it, but generally speaking, it keeps that connection from happening and thus enables the T cells to do their job and unleash hell on the cancer cells.  Turncoat thwarted, enemy defeated.  

No less than five major pharmaceutical companies are currently testing or investigating a PD-1 antibody: Bristol-Myers Squibb, Merck, Roche, GlaxoSmithKline, and Teva.  I take this as a good omen, since the first three companies employed me as a consultant at one point (hmmm, maybe that isn’t such a good sign after all). Initial trial indications are that PD-1 antibodies may be doubly effective at treating Stage 4 melanoma (and certain lung and kidney cancers) as current FDA-approved melanoma treatments Zelboraf and Yervoy. Trials are now being run to assess anti-PD-1 as a stand-alone treatment and in conjunction with the above drugs; mine is just the PD-1 antibody and only for patients who had a negative response to Zelboraf/Yervoy.  Being an immunotherapy medication, it also will keep me relatively healthy overall and work in conjunction with my immune system, which has remained remarkably strong through all of this.

So then, how did the first dose go?  Well, from an infusion standpoint, all went well – Jen and I even got to enjoy a little lunch date afterwards.  By early Friday evening, though, I definitely started to get flu-like symptoms, a known side effect.  The weekend felt like I got smacked on my rear from a nasty 48-hour flu; my hope is that this was my immune system kick-starting itself into high gear.  Much like a normal flu, the worst part was just feeling out of it for a day or two, but I bounced back by the time they teed off for the final round at Augusta. On Monday, I felt like I was back to 85% or so of 2013 T.J.’s normal health and energy level. 

We still have questions and more research to do regarding the interactions between the antibody and the immune system.  One doctor at Holy Cross really hit home when he told us, “I would not do anything that puts significant stress or exposure on your immune system.  This is an immunotherapy drug and it needs that system to do its job, so give it the chance to work by eliminating anything that can disrupt that.”  It really made us reconsider the often-busy life we lead and think about what really helps the body heal.

So the Phillies game I promised my daughter we were seeing on Sunday got axed – even after she told Jen on Saturday, “We are going to Phillies game!!”  Luckily a day at the beach makes even the most fanatical Phillies 3-year-old forget about baseball pretty quickly.  Lots of other “calendared items” are getting reviewed too, no easy task for a person who can’t sit still while someone, somewhere, is having fun.  (Shameless plug: we are still hoping to come up for the Melanoma International Foundation walk this Sunday, with the big “if I am 100%” caveat.  See for more info).  

While it is disappointing that the next few months will require lots of “No’s” and choosing to take it easy, the goal isn’t to make a few lasting memories this spring.  The goal is to achieve a durable response so there are many more lasting memories in the years to come.  If that means missing a few games, Josie and the Phils will understand.

T.J. Sharpe shares his fight against Stage 4 Melanoma in the Patient #1 blog. Read more »