Wednesday, September 6, 2017

Trial results from the use of the Ipi/Nivo in NED melanoma patients

Back in 2010 I was one of first 10 folks who made up the 33 melanoma participants in the Stage IV NED arm of a nivolumab (now called Opdivo) with peptide vaccines (They did nothing!!!  Here's that story: Peptide vaccines do NOT trigger effective immune reponse to melanoma!!!! Of mice and men....) phase 1 trial.  Our NED arm was compared to folks with active disease.  Ten NED peeps, and 10 with active disease, were given Nivo at 1mg/kg.  Later, since we didn't die or grow three heads, 10 more NED, 10 more with active disease were treated with nivo at 3mg/kg. Finally, 10 more were added to each arm , this time at 10 mg/kg.  We were all treated until progression or significant side effects, for a max of 2 1/2 years.
Here are the results, published in 2014, of my NED arm:  C'est moi!!! Results from the 33 ratties in my Nivolumb/Opdivo trial...published!
Here is a related post:  My Nivo (Opdivo) trial - first dose - 4 years ago 12/29/2010 - thoughts...

That trial morphed in all sorts of directions!  Arms were added that stopped giving the vaccines after we learned they were worthless. Important in that those peeps got to avoid the torture of the vaccines and in that it opened the trial to many more folks as the HLA typing required for the vaccines no longer limited participation.  Arms were created for folks who had already been treated with ipi. Additional arms gave the ipi/nivo combo to folks with active disease as well as those who were NED.

Having recently completed my annual scans, I duly contacted the person still managing the trial at Moffitt along with Dr. Weber and gave them the results.  Hell, if I'm gonna be a rattie....I want the data to be followed!!!!!!!!!!!!!!!
The latest data I had was this from 2016:   Udate on me and my ratties...from my 2 1/2 year, 2010 Opdivo/peptide vaccine trial at Moffitt - anti-PD1 as adjuvant. where I quoted:  The tote is that [there were] only 7 deaths in 33 patients with no deaths this year.  Only 2 deaths in the 40 subsequent patients.  Great record!"
And wrote this:  So there you have it, folks.  From the wizard himself.   These were 73 Stage IV melanoma patients, rendered NED via radiation and surgery, then treated with nivolumab (Opdivo).  Though we have sadly lost 9 of our tribe of ratties, many of us have now lived 6 years post that diagnosis.  Way past our previously expected shelf life!  Anti-PD1 products SHOULD be available to Stage III/IV NED patients, should they wish to use it.  We ratties have fought to prove its value! 

I asked for any up-dated info on my rattie peeps from the manager at Moffitt.  Don't know if that request was lost in translation, or if there just hasn't been any more tabulated, but the following is what she sent me:

Adjuvant nivolumab (NIVO) plus ipilimumab (IPI) for resected high-risk stages IIIC/IV melanoma (MEL).
Background: Patients (pts) with resected stage IIIC or IV melanoma are at very high-risk for recurrence and effective strategies for adjuvant therapy are needed. Combination NIVO + IPI yields high response rates but has a high rate of grades (G) 3-4 toxicities in advanced MEL. We examined the safety and efficacy of 2 dosing schedules of NIVO + IPI in resected stage IIIC and IV MEL pts. Methods: Resected stage IIIC/IV MEL pts who were free of disease, with adequate laboratory indices and performance status of 0-1 were treated with NIVO (1mg/kg) + IPI (3mg/kg) Q3 weeks X 4 doses (induction) followed by 2 years of NIVO at 3mg/kg Q2 weeks (Cohort A). Toxicities observed during induction led to opening of cohort B consisting of NIVO (3mg/kg) + IPI (1mg/kg) Q3 weeks X 4 doses followed by the same maintenance. Pre-defined criteria permitted initiation of NIVO maintenance following recovery from induction toxicity in both cohorts. Results: Twenty pts were treated in each cohort. Median age was 50 (22-78) in cohort A and 55 (29-77) in cohort B; stage IIIC pts constituted 65% and 60% of the respective cohorts. Toxicity precluded completion of all 4 induction doses in 50% in cohort A (most common was G3-4 ↑ AST and/or ALT in 7 pts) and 35% in cohort B. The most common G3-4 toxicities (minimum 5 events) are listed in the table. Hypophysitis developed in 28% (7 pts in cohort A). The incidence of ↑ AST/ALT, nausea, anorexia, cough, weight loss, neurotoxicity and endocrine toxicity was significantly higher in cohort A. In this group, 5 pts (25%) completed all induction doses and remain on NIVO maintenance; in group B, this number was 40%. There have been 4 relapses in cohort A, and 3 in cohort B. Only 1 pt in this high-risk study group has succumbed to MEL recurrence. At median follow-up of 21.3 months and 11 months respectively for the two cohorts, the median progression-free survival and overall survival have not been reached. Conclusions: In very high-risk resected MEL, adjuvant NIVO + IPI followed by maintenance NIVO has encouraging activity. Dosing per cohort B appears better tolerated and warrants further study.

So...not really 'new' as this was published in 2016 and not exactly what I was looking for as it is not from my cohort.  But....given the continued paucity of treatments allowed, other than ipi, for high risk NED melanoma peeps..and the good outcomes demonstrated...I thought it was worth sharing.  Hang in there ratties.  We're getting there!!!
P.S.  Will post any updated data specific to my ratties if I get it. - c


  1. New to this blog, and stunned by your thoroughness, candor and overall doing-good-in-the-world while sewing (check out when you have time on your hands). I'd like to read this article, (some days that's how I manage my anxiety). I have access to pubmed but I cannot find this article. Do you have the full citation?

  2. F/U - found it as an abstract - poster presentation - linked to first author. Thanks again.

  3. Thanks for all your hard work on making this matter easier to understand. My dad received his diagnosis about a year ago and I found your blog to be one of the best sources to keep up to date about the current state of melanoma treatments. It's very encouraging to read what kind of progress has been made in recent years.