Survival with dendritic cell vaccine about the same as survival produced with ipi

I have always, and still do, hold great hope for a vaccine that is REALLY effective for melanoma.  However, positive results have been few and far between.  My study was actually a combo of nivo and peptide vaccines.  In 2013, we ratties proved that those vaccines worked NOT AT ALL (and it is possible they even diminished our response by sequestering our t cells!!!):  Peptide vaccines do NOT trigger effective immune reponse to melanoma!!!! Of mice and men....

In 2015, there was this, on a different peptide vaccine:  Positive response to Helper Peptide Vaccines for melanoma

In 2016 there was a lot of talk about dendritic vaccines:  Dendritic cell vaccines. Perhaps this approach will allow vaccines to live up to their potential for melanoma....SOON!!!

Now there's this:

Twelve-year survival and immune correlates in dendritic cell-vaccinated melanoma patients. Gross, Erdmann, Haendle, et al. JCI Insight. 2017 Apr 20;2(8).

Reports on long-term (greater than/= to10 years) effects of cancer vaccines are missing. Therefore, in 2002, we initiated a phase I/II trial in cutaneous melanoma patients to further explore the immunogenicity of our DC vaccine and to establish its long-term toxicity and clinical benefit after a planned 10-year followup.

Monocyte-derived DCs matured by TNFα, IL-1β, IL-6, and PGE2 and then loaded with 4 HLA class I and 6 class II-restricted tumor peptides were injected intradermally in high doses over 2 years. We performed serial immunomonitoring in all 53 evaluable patients.

Vaccine-specific immune responses including high-affinity, IFNγ-producing CD4+ and lytic polyfunctional CD8+ T cells were de novo induced or boosted in most patients. Exposure of mature DCs to trimeric soluble CD40 ligand, unexpectedly, did not further enhance such immune responses, while keyhole limpet hemocyanin (KLH) pulsing to provide unspecific CD4+ help promoted CD8+ T cell responses - notably, their longevity. An unexpected 19% of nonresectable metastatic melanoma patients are still alive after 11 years, a survival rate similar to that observed in ipilimumab-treated patients and achieved without any major (more than grade 2) toxicity. Survival correlated significantly with the development of intense vaccine injection site reactions, and with blood eosinophilia after the first series of vaccinations, suggesting that prolonged survival was a consequence of DC vaccination.


Long-term survival in advanced melanoma patients undergoing DC vaccination is similar to ipilimumab-treated patients and occurs upon induction of tumor-specific T cells, blood eosinophilia, and strong vaccine injection site reactions occurring after the initial vaccinations.

And as far as those eosinophils???  Remember this?  Eosinophilia - biomarker for prognosis in melanoma and importance in immunotherapy response

With this level of response, dendritic vaccines certainly deliver something!  However, with a 40% response to anti-PD-1.....I would have a hard time picking ipi or these vaccines as my treatment if I had a choice.  Perhaps these vaccines WOULD be a good choice as adjuvant?  Perhaps as a combo with anti-PD-1?

Hang tough ratties.  We have a long way to go....but we've come a long way baby!!! - c

Efficacy of Pembro (Keytruda) in melanoma brain mets

I posted this report in March:   SRS with any systemic therapy helps response in melanoma...but anti-PD-1 WITH SRS = best OS in brain mets

While the data has made it clear that brain mets resolve best when treated with SRS and immunotherapy (anti-PD-1 in particular), [Check out this post: Brain mets in melanoma: Don't wait to add anti-PD1 to SRS!!! And....TILs correlates with extent of brain edema and survival time in patients with brain mets ] there have been many actual, as well as anecdotal, reports of patients who had untreated brain mets...which then resolved while on anti-PD-1 alone.  I happen to be one such patient (though I had already had a different brain met radiated) and here's a report addressing others, with additional links to more articles at the bottom of the post:  ASCO 2016 - Immunotherapy in melanoma brain mets  
One of the links directs you to this:  Nivo (Opdivo) with radiation = better for melanoma patients with brain mets  
And there is also this:  Yep! Immunotherapy can work in the brain...and pseudoprogression can be real!!

Now there is this:

Retrospective Analysis of the Efficacy of Pembrolizumab in Melanoma Patients With Brain Metastasis. Dagogo-Jack, Lanfanchi, Gainor, et al. J Immunother. 2017 Feb 17.

A total of 50% of patients with melanoma will develop brain metastasis (BM). Pembrolizumab was approved for treatment of metastatic melanoma on the basis of significant systemic antitumor activity. Because of low enrollment of patients with BM in pembrolizumab trials, efficacy against melanoma BM remains unknown. We reviewed records of 89 consecutive patients with melanoma treated with pembrolizumab at our institution between May 1, 2014 and October 31, 2015 to determine the time to progression. Thirty-six (40%) patients had BM before pembrolizumab. Twenty-six (72%) patients with BM had received prior treatment for BM. With median follow-up of 17.2 months, 54 patients (61%) developed progressive disease on pembrolizumab. Intracranial progression occurred in 19 patients (21%), 3 of whom did not have BM before treatment. Median time to progression at any site was 6 months for those without BM (n=53), 5 months for those with treated BM (n=26), and 1.2 months for patients with untreated BM (n=10). Using a Cox regression model adjusted for baseline factors, there was a statistically significant reduction in the hazard of progression for patients without BM and patients with treated BM compared with those with untreated BM. In conclusion, melanoma patients with pretreated BM can have durable systemic responses to pembrolizumab. Large, prospective studies are needed to evaluate the intracranial antitumor activity of pembrolizumab in melanoma patients with untreated BM.

Basically, this report simply confirms all of the above.  Anti-PD-1 (pembro/Keytruda or nivo/Opdivo) work in the brain.  They work better when combined with radiation.  

There!  I said it....AGAIN!!! - c

Sew Chaotically! - Me Made May - Week 1

Me Made May!  My way.  My makes paired with various other bits and pieces.  Here's Week One!

#MMM2017 kick off AND Melanoma Awareness month!  Target top and Me Made Skirt based on instructions from So Sew Easy 

Old Eddie Bauer skirt, rarely worn previously due to an unfortunate length, now hemmed and - Viola! - paired with a Me Made Colette Sorbetto 

Hand-me-down cords and Me Made M7093

Keeping cozy and comfy on a rainy spring day with rtw turtle and Me Made A-line skirt made when I first returned to sewing!

Since warm weather went away...had to pull out my Me Made Marled sweater  Speaking of staying warm....currently working on a new jean jacket.

Thinking of making another of these dresses - Lisette Passport Dress and jacket, maybe even in a textured knit...not sure how that would work.  But, it's a pretty sweet little pattern.  Meanwhile, keeping warm in a jacket a stole from B YEARS ago and refurbished here!  While STILL working on a new jean jacket....very, very slowly!  But, I think it will be worth the effort!!!

Tapas Time!  Wearing my Grainline Studio's Linden!

But my very, very, very best Me Mades (well, partly 'me' anyway!!!) are these:

Was lucky enough to spend a day hiking with Fred-o and his girl a couple of weeks ago!!!

And just this weekend got to help Roo celebrate her birthday with her Jamester!

She was even wearing a Me Made!!!  One of  Her Sobrettos!!!!

Happy Birthday, Rosie Roo!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!

Enjoy all your Me Mades....a sandwich, a garden, amazing peeps, a beautiful blouse, a smile your kindness brings, or even a crazy mess!!!  #mmm2017  #sewchaotically  #bestlifeever - les

Circulating tumor DNA provide valid way to monitor response to anti-PD-1 therapy for melanoma....AGAIN!!!

I keep reporting NEWS that is no longer NEWS!!!!   In March I posted this report which includes links to abstracts going back to 2014!  Circulating DNA predicts response to anti-PD1  "Well, 2014 is not so long ago," you say?  Not in melanoma world my friend!  3 years represents untold quantities of pain and suffering and loss of dear ratties!!!

So....here's the 'NEWS':

Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: a proof-of-concept study. Cabel, Riva, Servois, et al. Ann Oncol. 2017 Apr 29.

Recent clinical results support the use of new immune checkpoint blockers (ICB), such as anti-PD-1 (e.g. nivolumab, pembrolizumab) and anti-PD-L1 antibodies. Radiological evaluation of ICB efficacy during therapy is challenging due to tumor immune infiltration. Changes of circulating tumor DNA (ctDNA) levels during therapy could be a promising tool for very accurate monitoring of treatment efficacy, but data are lacking with ICB.

This prospective pilot study was conducted in patients with non-small cell lung cancer, uveal melanoma or microsatellite-instable colorectal cancer treated by nivolumab or pembrolizumab monotherapy at Institut Curie. ctDNA levels were assessed at baseline and after 8 weeks by bidirectional pyrophosphorolysis-activated polymerization, droplet digital PCR or next-generation sequencing depending on mutation type. Radiological evaluation of efficacy of treatment was performed by using immune-related response criteria.

ctDNA was detected at baseline in 10 out of 15 patients. At w8, a significant correlation was observed between synchronous changes in ctDNA levels and tumor size. Patients in whom ctDNA levels became undetectable at w8 presented a marked and lasting response to therapy. ctDNA detection at w8 was also a significant prognostic factor in terms of progression-free survival and overall survival. 

This proof-of-principle study is the first to demonstrate that quantitative ctDNA monitoring is a valuable tool to assess tumor response in patients treated with anti-PD-1 drugs.

Can we move forward...NOW!!!???  Week 8!!!  Institut Curie!!  (Of, course!) Hang tough, ratties! - c

Does previous treatment with BRAF inhibitors affect response to immunotherapy in melanoma?

We have had conflicting reports over the years regarding BRAF status and immunotherapy - to include:  "Those folks do better."  "Those folks do worse."  "It makes no difference."  Likewise, there has been conflict regarding which therapy to do first - immunotherapy or targeted therapy with BRAF inhibitors - for those who are BRAF positive. Now there is this:

Correlation between previous treatment with BRAF inhibitors and clinical response to pembrolizumab in patients with advanced melanoma. Simeone, Grimaldi, Restino, et al. Oncoimmunology. 2017 Jan 19.

The optimal sequencing of targeted treatment and immunotherapy in the treatment of advanced melanoma is a key question and prospective studies to address this are ongoing. Previous observations suggest that treating first with targeted therapy may select for more aggressive disease, meaning that patients may not gain full benefit from subsequent immunotherapy. In a single-center retrospective analysis, we investigated whether response to pembrolizumab was affected by previous BRAF inhibitor therapy. A total of 42 patients with metastatic cutaneous or mucosal melanoma who had received previous treatment with ipilimumab were treated with pembrolizumab as part of the Italian expanded access program. Sixteen of these patients had BRAF-mutated melanoma and had also been previously treated with a BRAF inhibitor (vemurafenib or dabrafenib), while 26 had BRAF wild-type melanoma (no previous BRAF inhibitor). Patients with BRAF-mutant melanoma who were previously treated with BRAF inhibitors had a significantly lower median progression-free survival (3 versus not reached mo) and disease control rate (18.6% versus 65.4%;) than patients with BRAF wild-type, while there was also a trend toward a lower response rate (assessed using immune-related response criteria) although this was not significantly different between groups (12.5% versus 36.4%;). These data are consistent with previous reports that BRAF inhibitor therapy may affect subsequent response to immunotherapy.

Hmmm....  Not sure this is terribly elucidating.  I fear the "facts" in this report are much confounded!

1.   It would not surprise me to find that one day we consider mucosal melanoma and cutaneous melanoma to be two different diseases.  They are certainly not apples to apples.
2.  Pretreatment with ipi is KNOWN to decrease the response to anti-PD-1 (Pembro/Ketruda and Nivo/Opdivo)!  Remember this?  Sequential nivo then ipi = ORR of 41%. Ipi followed by nivo = ORR of 20%!!!! FDA! Are you listening???????
3.  Also, BRAF wild-type vs BRAF mutated - again, not apples to apples.
4.  What we need is a study in which one group of folks with cutaneous melanoma (or strictly mucosal melanoma) with BRAF positive status are treated with targeted therapy then given anti-PD-1 vs another BRAF positive group of folks are treated with anti-PD-1 followed by BRAFi.

It's just me, but... C'mon man!!!!  Hang in there, ratties!  - c

Sew Chaotically! - Melanoma Awareness Month/Day AND #MMMay 2017 ~ or ~ M6886 - It's a dress, it's a skirt, it's....crazy land!????

May.  Melanoma Awareness Month.  Also happens to be:  Ichthyosis awareness month!  What the heck????  Too much skin crap and too little time, I guess!  Do check out this lovely lady's post (link above).  Rochelle is an amazing sewist, knitter, designer, dog lover, kid camp mentor, writer, and survivor!  Definitely worth your time!!

Everybody's going thru something, right???  Sometimes, that something is more (or less) obvious to others.  No matter how close to death I have been with lung and brain mets, I've never looked particularly ill.  I always imagined what folks thought of me, as we were all waiting like sheep, some bald and shorn, others not, in various oncology, radiology, and surgical waiting rooms.  At times I thought, I could hear, "Damn.  She looks good!  I can do that.  I can get through this. If she did it, I can do it!!!"  At other times, the sad smiles that came my way felt like, "Oh, look at her.  She is going to be getting some tough news today.  I hope she can handle it.  She has no idea what's in 
store."  After work, I tell B that today happens to be Melanoma Awareness Day and one was to wear black in honor, and remembrance, of same.  With a bit of a growl, he replied, "I have melanoma awareness EVERY day."  While I continue to placidly eat my Chinese take away, he adds, "So, is that why you wore this today?" "Yep," I say, "though no one a'tall knew why."  Which is perhaps...NOT the point...but now you do.

But, being the goofy weird-o, a-girl's-gotta-have-fun, chick that I am....I also wore it because of this:
#MMMay17!!!  That would be "Me Made May 2017!"  But, subversive that I also am.....I'm not going balls to the wall, Me Made For Real! - just...kind'a.  I am going to try to participate in "Me Made May" for the first time.  For the uninitiated, one is supposed to wear only Me Made garments for the entire month.  I am going to try to wear something Me Made daily, but not exclusively.  No, I will not have made my shoes or under pinnings.  Many times, my Me Made garments will be paired with items purchased (swoon not, my Me Made Die Hards!!!) from Target or J Crew.  Sew....here we go!!!!

I wear black for Melanoma Awareness Day AND Me Made MAY!!!!

I got this lovely, rather substantial striped ponte from Mood sometime back.  I was really tempted to make another t-shirt dress.....but....

I made a skirt!  (Actually, I made two!!  One went to Roo!)

NO!  A dress!!!

Hee hee!!!

I made a top and a skirt...and a dress (if I wear them together)!!  Figuring that this way, I'd get the best of both worlds!

McCall's 6886 again, having already used it to make My very first T-shirt dress and my more recent bamboo version - I shortened it to make the top!!!

For the skirt, I used this excellent tutorial I first tried HERE! - The 30 minute skirt pattern From So Sew Easy! pegged in a bit at the hem and tweaked just for me!

So whatever skin is yours to live in, I wish you as much comfort and joy as possible.  We only get one go.  Hang in there.  Play hard.  Live big.  And make each day, a custom fit ME MADE.... whatever that means for you!  Much love, les

Across SEVEN Aprils!!!

WOW!  Who would'a thunk it?  Seven years ago today the right upper lobe of my lung was removed three days after having had another melanoma met zapped in my brain.  Here's are some of ~ My Aprils

April ~ Perhaps the most beautiful month on my mountain.  April 2010 ~ The month my melanoma journey devolved into complete chaos after having already dealt with the beast for 7 years.  April 1861 ~ The Civil War began.  Across Five Aprils ~ Irene Hunt's beautiful story of the Creighton family, struggling to survive as their country and family were torn apart in the border state of Illinois during all the years of the Civil War.  April 11, 1865 ~ Two days after General Lee's surrender, Abraham Lincoln began his last speech, "We meet this evening, not in sorrow, but in gladness of heart."  April 14, 1865 ~ Lincoln was shot by John Wilkes Booth at a theater in Washington D.C.  He died the next day.  April 2010 ~ I started this blog.  Writing this: Chaotically Precise  And this: Life  April 2017 ~ Fourteen years after a melanoma diagnosis.  7 years Stage IV.  I am here.  Still...

So.....here is my view THIS April...from my bit of mountain...

No matter where you are, no matter what position you currently find yourself in...  Happy Spring! Too often, my melanoma peeps endure an incredibly difficult civil war within. However, there is beauty, there is hope, there is strength others can share when we are too tired to go it alone.  My Bentie's love and care are in full bloom each day of every year...but never more pointedly than now....through the cherry trees he planted...for me...ten years ago...

They bloom for you, too.  ...Not in sorrow, but in gladness of heart. ~ love, les