Wednesday, December 31, 2014

My Nivo (Opdivo) trial - first dose - 4 years ago 12/29/2010 - thoughts...

 How very strange it is to look back!!!  4 years.  It seems like yesterday.  It seems like ages ago.  Anti-PD1 was an unknown.  Only a handful of patients had taken it in a couple of studies.  Neither ipi (yervoy) nor the BRAF inhibitors were FDA approved.  The Merck product, Keytruda, did not exist.  I am surprised to be here.  I can hardly believe I, and my fellow ratties, managed the every other week routine for 6 months:  Work 12 hours shifts Mon, Tue, Wed.  Drive to Atlanta on Thurs.  Fly to Tampa.  Get rental car and dinner.  Rest up at the good ol' La Quinta.  Friday am - Hop over to Moffitt at the butt crack of dawn for labs, office visit, injections, infusion.  Drive like mad back to the air port.  Fly to Atlanta.  Drive the two hours back to Chattanooga.  Back to work on Monday.  I've since discovered that many in my trial did not work during their treatment.  Though, some did and many continue their busy lives today while taking Keytruda as well as ipi combined with nivo!  For the remaining two years, Tampa visits and infusions were just every 12 weeks.  It seemed like a holiday!  I missed three work days over those 2 1/2 years.  There are those who said I was nuts and would have demonstrated better judgment by taking off more...but that's not how I roll.  And I was so lucky.  Lucky to be in the trial.  Lucky to be able to AFFORD to be in the trial.  Lucky to be NED going into it.  Lucky to have the support system I had while dealing with it.  Lucky for my battalion who marches with me...still.

It is hard to say what I thought would happen.  I really didn't expect much.  I certainly didn't look upon Nivo as my "cure" as so many seem to today on various boards, chat groups and forums.  Don't get me wrong.  I was thankful for the option.  Brain mets, lung mets, tonsilar mets, another brain met in rapid succession had made me well aware that something was desperately needed to break that cycle.  My only options were IL2 or interferon, since after every met, surgery rendered me NED....a boon and a reason to be refused from every other trial!  I still don't know what my future holds.  But, neither does anyone else.  I just worry about those who seem so certain that the anti-PD1 drugs will be their personal deliverance when the 30-40% response rate tells us that there are a large number of us who will be disappointed.

Having spent a lifetime reading research reports, case studies... it is surreal to read one that you know refers to your own experience.  It seems cold.  A little wrong somehow. "33 patients were enrolled.  10/33 patients relapsed. Of the 10 relapsed patients, five died due to metastatic melanoma; three were rendered free of disease surgically and remain disease-free at 2, 27 and 54 weeks after relapse.  One patient had spontaneous regression...and has been free of disease for over 3 years.  One additional relapsed patient is alive and on active therapy with dabrafenib plus trametinib."

My thoughts about the report and results:

SIDE EFFECTS:
"Nivolumab with vaccine is well tolerated as adjuvant therapy and demonstrated immunologic activity with promising survival in high-risk resected melanoma..."  Well tolerated?  Hmmm....  As compared to what?  A relaxing day of hikes along mountain trails, followed by a warm shower, good book by a cozy fire and delicious dinner?  Arsenic?  Dick Cheney's idea of simple Q & A?  There is no doubt that many have endured far more difficult treatments.  Still vaccine injection site reaction, fatigue, rash, itching, nausea, diarrhea and arthralgias were common.  Hypokalemia (low potassium...something that can be life threatening), enteritis, colitis, hypophysitis, and thyroiditis were certainly no fun for some of my fellow ratties.  There was one patient with grade 1 pneumonititis. Wonder who that was?  Maybe me, maybe not.  It is very strange to have those who do not have melanoma, have never been given those miserable vaccines or taken anti-PD1 even once, determine the quality of another's experience.

BRAIN METS:
"Ten patients had resected brain metastases."  Well...that's not entirely accurate.  Mine was not "resected" it was zapped via stereotactic radiation.  Not certain about anyone else.   Only 2 of these ten patients have relapsed.  One developed a lung met which was resected and she remains NED.  The other apparently had significant CNS disease at induction, though researchers were unaware at the time, "and expired 3 weeks from initiation."  Despite such a loss, this is a pretty remarkable outcome for folks post melanoma brain mets, given our shelf-life of just 6 months or so without treatment.

RADIATION:
"Radiation therapy was administered to 18 patients prior to or after surgery including nine with resected brain metastases." The study doesn't speculate and all I can do is that...but with more and more research looking at retrospective data and new studies specifically examining radiation combined with ipi, anti-PD1 and the BRAF inhibitors...I have to believe that this combo is working positively for those zapped ratties in my trial.  (Much more to come on this topic in 2015!!)

PD-L1
There have been hopes that testing tumors for various biomarkers would tell docs which patients would respond to which drug.  PD-L1 was one of those. 28 of us had our tumors tested.  I still don't know what mine showed.  But, in our study, "there was no significant association between PD-L1 and relapse free survival in this patient population, although there is a non-statistically significant trend towards better RFS in those whose tumors were PD-L1 positive..."  For whatever that is worth.  I suspect the test for PD-L1 is not quite good enough just yet and there is more to be learned on this subject.

MDSC  (myeloid derived suppressor cells)
"There was a trend towards lower baseline MDSC levels in non-relapsing patients compared to relapsing patients."  This bit of stuff and such along with other Treg/Tcell data comes your way thanks to us ratties sitting through leukapheresis twice during the trial. However, this is a bit I'm pretty psyched about.  There is talk among melanoma big dogs that combining anti-PD1 with MDSC or T-reg depletion would make it more effective.  I think that holds real promise.  Though...once again...despite my blood and services having been rendered....I have no idea what my MDSC levels were.  Still...I think this could be a real boon to future patients.

RELAPSE FREE SURVIVAL:
"A retrospective study....showed a median overall survival of 12 months in stage IV melanoma patients undergoing metastasectomy."  Yet, my ratties and I have demonstrated an "impressive relapse-free survival...of 47.1 months and a median overall survival not yet reached with over 32 months of follow-up."  For me, I am now: 
136 months post melanoma diagnosis
56 months post Stage IV melanoma
50 months NED
48 months post start of nivo/Opdivo trial
18 months post my last infusion

It has been a strange, yet wonderful ride.  Here's to the ratties!  Here's to 2015! Much love - c


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