Saturday, January 24, 2015

Good news for NRAS positive folks, especially in regard to anti-PD1!!!!

Abstract presented at the American Association for Cancer Research, April 2014

NRAS mutation as a predictor of response to immune-based therapies in patients with metastatic melanoma.  Iams, Johnson, Flavin, Zhao, Sosman, et al.

"Immune based therapies are playing an expanding role in the treatment of advanced melanoma.  Reliable biomarkers to predict benefit from these agents have not yet been identified....  Approximately 15-20% of patients with melanoma harbor an NRAS mutation...  We assessed whether NRAS mutations impact the response to immune-based therapy..."

Examined 171 patients from 3 institutions with advanced melanoma and known tumor genotype.  All were treated with either IL-2, anti-CTLA-4 (ipi/yervoy), or anti-PD1lPD-L1 inhibitors.  "We compared the rates of clinical response between patients with NRAS mutant melanoma and those without NRAS or BRAF mutations (wild type)..." 

End points: CR = Complete Response, PR = partial response.  Secondary end points:  CB = clinical benefit (defined as CR/PR or stable disease for more than 24 weeks), PFS = progression free survival, and OS = overall survival.

59 patients (35%) had NRAS-mutant melanoma.  112 patients (65%) had WT (wild type)... There was a significantly higher rate of CR/PR and CB in patients with NRAS vs  patients with WT melanoma.  (32% vs 18% for CR/PR and 49% vs 29% for CB).  "Within specific immune therapy types, patients with NRAS-mutant melanoma experienced the greatest benefit in CR/PR compared to patients with WT melanoma when treated with anti-PD1/PD-L1 agents (70% vs 20%)."  No statistically significant differences in median PFS or median OS were observed.

Conclusion:  Patients with NRAS mutation experience a higher rate of CR/PR and CB when treated with immune-based therapy vs patients with WT.  Data suggest that routine assessment for NRAS mutations in patients with melanoma is warranted.

A ray of light for folks with NRAS mutation. And maybe one more reason not to make them go through ipi before they get to take anti-PD1???!!!!!  Best - c

Thursday, January 22, 2015

Vitiligo....a good prognostic indicator for melanoma!

Just after my fourth dose of Nivolumab I noticed white patches beginning to develop on my hands.  Previous studies report this form of vitiligo occurs in 5-9% of patients given ipi or anti-PD1.  It can also occur in patients who have taken IL2 as well as spontaneously in the general population. For comparison, its incidence in whites in the United States is 0.4%.  Here's some info I've posted about vitiligo before:  General info about vitiligo and vitiligo in mice with melanoma

A newly published article reviewed human ratties with melanoma, immunotherapy and vitiligo:

Vitiligo-like depigmentation in patients with stage III-IV melanoma receiving immunotherapy and its association with survival:  A systematic review and meta-analysis.  Teulings, Limpen, Jansen, et al.  2015 American Society of Clinical Oncology.

The authors "searched and selected all studies on melanoma immunotherapy that reported on autoimmune toxicity and/or vitiligo between 1995 and 2013."  "One hundred thirty-seven studies....comprising 139 treatment arms....including a total of 5,737 patients.  The overall incidence of vitiligo was 3.4%....vitiligo development was significantly associated with both progression-free survival and overall survival, indicating that these patients have two to four times less risk of disease progression and death, respectively, compared with patients without vitiligo development."

OK all you smart people out there!! Mary Jo Turk....that means you, too!!!  Let's figure out how to make vitiligo happen.  What causes it...really?  How can we induce it in more patients? 

If we can give vitiligo to mice...let's do the same for the human ratties!!!!

vitiligo pics in 2013...I know...weird, right?

Vitiligo pics in 2014

To a whiter shade of pale! - c

Sunday, January 18, 2015

CEACAM1

I find the relatively new trend of patients and families "discovering" new medications and treatments via press releases by companies in business rags, Forbes, etc. rather than medical journals, scientific publications, and their doctors rather disturbing.  Don't get me wrong.  I am all for spreading the news about the next great drug in as many ways and to as many folks as possible.  It's just that when company claims regarding treatments and cures are published as investment propaganda for stockbrokers and market watchers, patients have no way of knowing if the product is REALLY going to be a possible cure or just more snake oil a company is happy to make money on until the ratties prove its effectiveness or....not.

CEACAM1 has made a splash in just this way.  (See the technews link below.)  However, since some folks wrote to ask me about it and it made news on a couple of forums, I decided to try to find out what all the fuss was about.  It wasn't that easy.  In my research I discovered that CEACAM1 is a molecule that affects adhesion of cells to other cells, the formation of blood vessels, and has interaction with lymphocyte function.  It has opposing effects in different cancers.  In breast cancer, it seems that the more you have of it, the better.  In melanoma, the more you have, the worse your prognosis.  In  fact, in melanoma it can be used as a prognostic marker...with greater predictive ability than Breslow levels.  There is some pre-clinical evidence that blocking CEACAM1 with an antibody will enhance t-cell function against the tumor. The only real 'study' I could find was an examination in mice and Petri dishes from 2012 (link also below).

Novel immunotherapy for malignant melanoma with a monocolonal antibody that blocks CEACAM1 homophilic interactions.  Ortenberg, Sapir, Raz, et al.  Mol Cancer Ther. June, 2012.

"CEACAM1 was reported as a strong clinical predictor of poor prognosis in melanoma.  We have previously identified CEACAM1 as a tumor escape mechanism from cytotoxic lymphocytes. ....we present substantial evidence in vitro and in vivo that blocking of CEACAM1 function with a novel monoclonal antibody (MRG1) is a promising strategy for cancer immunotherapy.  ...MRG1 is a potent inhibitor of CEACAM1 homophilic binding and does not induce any agonistic effect. We show using cytotoxicity assays that MRG1 renders multiple melanoma cell lines more vulnerable to T cells in a dose-dependent manner...  It is shown that MRG1 reaches the tumor and is cleared within a week.  ...approximately 90% of melanoma specimens are CEACAM1 positive, implying that the majority of patients with melanoma could be amenable to MRG1 based therapy.  ...MRG1 does not directly affect CEACAM1 positive cells.  CEACAM1 blockade is different from other immunomodulatory approaches as MRG1 targets inhibitory interactions between tumor cells and late effector lymphocytes, which is thus a more specific and compartmentalized immune stimulation with potentially superior safety profile."

Regarding the question of upcoming trials:  They are reported to be starting at Yale and UCLA in the first quarter of 2015.  Dr. Ribas is one of the researchers.  There is no posting on clinicaltrials.gov yet.  

technews reports on CEACAM1 

abstract of CEACAM1 study in Molecular Cancer Therapeutics from 2012 

If CEACAM1 inhibition is the next big thing to help melanoma patients...that will be awesome.   Hang in there, ratties.  It may be a crazy ride.  - c

Wednesday, January 14, 2015

Clap along if you feel like happiness is the truth...with a post-script...


NOTE:  I don't know if this is a preface....  Is that what is written to begin a piece after the piece is written?  A post-script?  Can a post-script come at the beginning???  Can you tell I'm stalling?  I wrote this bit Saturday afternoon...right after a good work-out, while teasing my daughter, flirting with my B, genuinely happy, looking forward, smiling...planning to proof and post a little later after letting things "take" a minute.  Then, there were killings in France.  Little girls used as suicide bombers in Nigeria by Boko Haram.  Folks I've had direct correspondence with are not doing well.  Dear ones face February....though they seem strong.  Children lose their beautiful mom to melanoma.  Those near and dear suffer from the senseless spite and meanness of others.  I am not so happy at just this minute. I almost decided not to post it, lest it appear unseemly listed along side those who are so gravely suffering. Fearing it will not ring true since I am no longer really in the mood.  After thinking about it all day, I decided.  NOPE.  I will post it.  It may be even more important NOW.  I am NOT always happy.  One would have to be decidedly unhinged to be so.  However, I think those moments of joy and release that we all so need and deserve in our lives, are much more easily attained and appreciated when granted, if we actually think about happiness.  Specifically examine what it is that makes us happy.  Unless we do, I fear we will not seek it, nor recognize its full beauty when it comes.  So....for all of you who had a wonderful, iridescent floating bubble of a day...ENJOY!!!  Dance in your underwear like you just don't care!!!  It makes me smile to picture it!  For those of you dealing with hurt and loneliness, a heart torn right in two, with impossible anguish and fear...tears are in my eyes for you.  I would do ANYTHING to fix it, to take away your pain...but I cannot.  I can only offer this....
 
"It might seem crazy what I'm about to say!"  But, when this song comes on as the last one playing during your workout - you know it's a good day.  "Clap along if you know what happiness is to you!"


What IS happiness to you?  For me happiness is....

The right song at the right time.
Babies who coo and giggle.
Children who haven't learned to be embarrassed and fear sharing their hopes and dreams.
Adults who refuse to be embarrassed and fear sharing their hopes and dreams.
Laughing like a hyena...often without being able to explain what was so funny.
When the words get it right.
When I think, maybe, I did some good.
When those who know me still like me.
When those who say they know me....REALLY do.
A happy accident of a recipe...eggplant involtini as a layered, baked masterpiece!
Holding my own with the smartest peeps I know!
ESPN! (No...not THAT one!!)
Going for it...no holds barred.
Dancing!  The more participants and the loonier the better.
Singing!
Driving to the next adventure.
When all my friends automatically pass the gravy and mashed potatoes down to me!
The sound of a mountain stream as it rushes to a suddenly quiet and reflective pool.
Moss and fairies.
Herbs and flowers.
When running feels free.
When someone does something wise, generous, fine, and important....and they didn't have to.

And finally....amazing, beautiful, collisions....of friends...who have never met, who know your heart, and while in the midst (RIGHT HERE!!!  In the slap-dab MIDST, I TELL YOU!!!!) of writing this very post...Roo comes rushing in....wearing....HAPPINESS!


Thanks Jeanne and Kidlet!  You have no idea...but then again, you probably do....how happy an owl hat can make someone!!!  Much love to you both!!! Peace and love to all of you. - c

Happy
It might seem crazy what I'm about to say
Sunshine she's here, you can take away
I'm a hot air balloon, I could go to space
With the air, like I don't care baby by the way
Because I'm happy
Clap along if you feel like a room without a roof
Because I'm happy
Clap along if you feel like happiness is the truth
Because I'm happy
Clap along if you know what happiness is to you
Because I'm happy
Clap along if you feel like that's what you wanna do
Here come bad news talking this and that
Yeah, give me all you got, don't hold back
Yeah, well I should probably warn you I'll be just fine
Yeah, no offense to you don't waste your time
Here's why
Because I'm happy
Clap along if you feel like a room without a roof
Because I'm happy
Clap along…

Saturday, January 10, 2015

THIS....is how you fight cancer!!!!


Stuart Scott.  1965-2015.  Passing from our world after dealing with a rare form of appendiceal cancer for 10 years, he truly proved to be 'as cool as the other side of the pillow'!!!!

Stuart Scott's ESPYS Speech

"Our life's journey is about the people that touch us...  Don't give up.  Don't ever give up.  When you die, that does not mean that you lose to cancer.  You beat cancer by how you live, why you live, and in the manner in which you live. So live!  Live!!  Fight like hell!  And when you get too tired to fight, then lay down, and rest.  And let somebody else fight for you. This whole journey thing - is not a solo venture.  This is something that REQUIRES support.” ~Stuart Scott~

So wise.  So beautiful.  Such a loss.  What a man.  How lucky are we to have heard his words?  How lucky am I to have the support of my battalion... such that my journey is NOT a solo venture?!
Boo yah!!!  - c

Wednesday, January 7, 2015

A beautiful lady, with eloquent, though heartbreaking words re: clinical trials....


This lovely lady sums up so much I feel about clinical trials more eloquently than I ever will!  Please look and listen:

  Lori Murdock, Stage IV melanoma, Clinical Trial survivor

How sadly recognizable her recounting of her oncologist's response to, "Okay, where do we go from here?  I've heard about clinical trials.  There must be some available.  And he said, 'Well, I could have a look'."  At which point it became abundantly clear that the only person she had in her corner was her!!  Granted, ipi (Yervoy) was not FDA approved when I first needed treatment, but the ONLY human who explored clinical trials, beat the bushes, called every oncologist this side of Texas and in Germany to boot, was Bentie. Neither of my local oncologists did.  Had I not had him fighting for me, I really don't know that I could have been as cool as this lady.  I don't know that I could have done the research and kept beating against all the closed doors myself.

Dacarbazine (DTIC).  Hmmm...  Don't forget what Weber said about Dacarbazine:  "...when talking about some of these trial options with Dr. Weber, he acknowledged that had ipi or anti-PD1 had been discovered first....Dacarbazine would never have attained FDA approval...yet, we continue to use it.  Incredible."

And, what the hell???  What sort of (un)ethical behavior did her onc feel he was free to demonstrate when he sent her a letter saying that if he was to refer her to another trial, then she "needed to give them some reassurance that [she] would accept whatever drug [she] was allocated to." Patients agree to participate in a trial or not.  Patients have the right to decline trial participation at any time.  What reputable doctor would twist a patient's arm, holding additional referrals hostage, in order to push a patient to REPEAT a drug they have already taken and not only failed to have their tumors respond to, but became ill in the process, while facing an ever looming death sentence from their disease?  Too many, I'm afraid.  And, if you expect me to believe that they are not subsidized by Big Pharma???? That is never gonna happen!  Don't get me wrong.  There are wonderful docs out there, fighting for their patients...Big Pharma be damned!  Unfortunately, there are many who are not.

"I feel that it is unethical to present an arm to a patient, which everybody knows isn't going to be of help."  "Therefore, if you've had previous phases of a clinical trial that has indicated a good response and you put that up against 'something' that you know isn't going to work, there is an immediate conflict of interest.  An immediate imbalance arises...it becomes unethical."   

"I want my voice to be heard.  I want clinical trial designers, drug companies, I want everybody to know - how hard it is to know there are drugs out there and you can't get them.  I'd like them to try and explain it to my children, cause I find it very difficult."

Dear Lori,
I don't know if it helps...but I hear your words.  I feel your pain.  I continue to fight for myself and you and others ~ for the right to balanced, reasonable, transparent trial options.  Perhaps, a few more will hear your words and be moved by your indomitable spirit, as I have been, through my posting your video here.  I wish you love and hope. - c

Sunday, January 4, 2015

2015: CONTINUING...or as I like to say...We begin again...


Looking forward to a new year induces me to look back as well.  Who have I become in this last year?  In these past 50 years?  What have I gained?  Lost?  Any new skill sets...tangible or emotional?  What has the M-elephant in the room taken?  Given?  What AM I looking forward to....tomorrow?  Next week?  Next year?  I don't claim to be able to answer all my own questions, but here are some things that I've been thinking about.  They feel very wise to me...

In his book, Traveling Light, Daniel J. O’Leary quotes Bearwatcher, an Apache medicine man...
In the Apache language there is no word for ‘guilt.’ Our lives are like diamonds. When we are born we are pure and uncut. Each thing that happens to us in our lives teaches us how to reflect the light in the world; each experience gives us a new cut, a new facet in our diamond. How brilliantly do those diamonds sparkle whose facets are many, to whom life has given many cuts.
From Rent, Seasons of Love ~ Jonathan Larson

Five hundred twenty-five thousand
Six hundred minutes
Five hundred twenty-five thousand
Moments so dear

Five hundred twenty-five thousand
Six hundred minutes
How do you measure, measure a year?

In daylights, in sunsets
In midnights, in cups of coffee
In inches, in miles
In laughter, in strife?

In five hundred twenty-five thousand
Six hundred minutes
How do you measure a year in the life?

Five hundred twenty-five thousand
Six hundred minutes
How do you measure the life
Of a woman or man?

In truths that she learned?
Or in times that he cried?
In bridges he burned?
Or the way that she died?

It's time now to sing out
Though the story never ends
Let's celebrate, remember a year
In the life of friends.

Remember the love.
Measure in love.
Seasons of love.

And then there are these words from another wise sage, My Bentie:

We are starting, no, continuing our lives. It is not a fresh start, but one on the same trail. We have turned around to see where we have already been, a wonder and turn, to move on with hope. May dragonflies lead your way! 


Shine bright, like a diamond.  Measure in love.  And may there be dragonflies for all of you, my friends.  Happy New Year!!! - c