My anti-PD1/vaccine trial "results"

I am now more than 21 months into my Stage IV, NED (resected), 1mg/kg anti-PD1 (MDX-1106 or BMS-936558...your choice) trial with peptide vaccines at Moffitt.  For those of you just tuning in:  I have been considered a Stage IV melanoma patient for 35 months and was first diagnosed with melanoma in 2003.  I have never had any treatments other than this one and surgeries.

We did our usual Thurs/Fri trip to Tampa and all was well.  There was the fun, the silly, and the sad as usual, but for now, here are the things we learned.

OUTCOMES at this point in my cohort:  So far, it seems, as I reported in June, two patients died early on in the trial.  One of the deaths was subsequent to brain mets that had not been noted when they entered the trial and I am not certain of the cause of death in the second. In total, 6 patients out of the 29, have progressed. One, whom I've mentioned before, experienced spontaneous regression while being watched to determine treatment, and continues to remain stable with NO ADDITIONAL TREATMENT given as yet.  The other 5 are reported to be doing well on regimens of ipi (now yervoy) or BRAF inhibitors. The remaining 21 of us....carry on.

Dr. Weber remained positive about these results, saying, basically, that given the expectations of survival in this high-risk group we were "doing better than predicted" and based on historical data, after 6 months, at least half of us in this group would have been expected to relapse.  In other words, at least 15 of us would have been expected to relapse prior to this point in the study.  (See slide on next post.)

Sadly, these outcomes remain "excellent" in melanoma world.  Dr. Weber has already determined in prior work, that ipi as an adjuvant treatment for Stage IV, resected melanoma patients, produces at least a 60% survival over 5 years, so one could expect that anti-PD1 therapy which has triple the response rate of ipi, would have similar or better results.  Obviously, we lab rats have yet to prove that out.

For more on that point, check out the article:
Extended dose ipilimumab with a peptide vaccine:  immune correlates associated with clinical benefits in patients with resected high-risk stage IIIC/IV melanoma.  Journal of Clinical Cancer Research, 2011, February 15.  Authors:  Sarniak, A.A., Weber, J.S. (and others).

Which basically states, "Adjunct [ipi] following resection of melanoma at high risk of relapse appeared to be associated with improved outcome compared to historical reports."  (See set of slides in upcoming post.)

The only other solid point we discovered about my trial in particular was in regard to the vaccine component.  I asked Weber why he had decided to use the vaccines in addition to anti-PD1 in my trial as well as in some of the new ones at Moffitt.  He stated that he was just using them to generate antigen specific T-cells so that they can be utilized as indicators of the effects of anti-PD1 on T-cells.  When I asked how that was working out, he replied that the dosage levels (1, 3, and 10mg/kg in my group) showed no increased effect on T-cells as the dosage increased.  A little disconcerting for folks thinking they might get more benefit with greater quantities of medication.  (Although this was already being proven in the prior study of anti-PD1 that I reported on earlier.) Also a bit disconcerting for those of us who thought perhaps we would acquire a double whammy with which to attack our melanoma with the combined effect of the vaccines and anti-PD1. These same vaccines were used in combination with ipi in a prior study and demonstrated no effect.  However, Brent continues to hope that for some folks, a positive effect from the peptide vaccines is there...if hard to calculate...since they did work for the mice!!!

See slides...next.... c