MPIP: Melanoma Patients Information Page

The MPIP is the oldest and largest community of people affected by melanoma hosted through the Melanoma Research Foundation. It is designed to provide support and information to caregivers, patients, family and friends. Once you have been touched by melanoma—either as a patient or as a family member or friend of a patient—you become part of a community. It is not a community anyone joins willingly. But if you must be part of this group, you will find no better place to find the tools you need in your journey with this cancer, and the friends who can make that journey more bearable.

The information on the bulletin board is open and accessible to everyone. To add a new topic or to post a reply, you must be a registered user. Please note that you will be able to post both topics and replies anonymously even though you are logged in. All posts must abide by MRF posting policies.

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Replies by: LynnLuc, melissa ann

Anti-PD-1 (BMS-936558, MDX-1106) in patients with advanced solid tumors: Clinical activity, safety, and a potential biomarker for response.
Suzanne Topalian, MD Johns Hopkins University School of Medicine Baltimore, MD

 

Video at The ASCO 2012 Meeting

Anti-PD-1 (BMS-936558, MDX-1106) 

 I have been following this new treatment for a number of years and am trying to get my arms around the science. 

When a T-cell is activated, the PD-1 , CTLA-4, ICOS, and others molecules are expressed and upregulated to the surface of the T-cell. Both PD-1 and CTLA-4 are checkpoint molecules that regulate the immune response. They are inhibitory to the point that they can shut down T-cell activation. ICOS on the other hand is a costimulatory molecule that is needed, along with IL-2 to keep the T-cell activated and help proliferate the T-cells.Elevated levels of ICOS mRNA can be detected already one hour after TCR engagement, followed by surface expression within 12 hours. Protein expression reaches a maximum after 48 hours and declines then slightly.

It has been shown that ICOS is inducible within 48 hours of T-cell activation on both CD4+ and CD8+ cells; after; CD28 signaling; whereas cytotoxic T lymphocyte  antigen-4 (CTLA-4) ligation prevents its upregulation. 

First, CTLA-4 engagement on resting T-cells was found to indirectly block ICOS costimulation by interferring with the signals needed to induce ICOS cell surface expression. Second, on preactivated cells that had high levels of ICOS expression, CTLA-4 ligation blocked the ICOS-mediated induction of IL-4, IL-10, and IL-13, suggesting an interference with downstream signaling pathways. The addition of IL-2 not only overcame both mechanisms, but also greatly augmented the level of cellular activation suggesting synergy between ICOS and IL-2 signalling.

So after T-cell Activation, IFN gamma is secreted (30 minutes then IL-2 is secreted (45 minutes in) and so on ...

 

The surface expression of ICOS is within 12 hours of activation. Since CTLA-4 blocks ICOS costimulation, Yervoy (anti-CTLA-4) must be used to counter the surpressive signalling. PD-1 also upregulates to the surface in the early activation process. PD-1 is upregulated within 24h after T cell activation, PD1-Mediated Suppression of IL->2 Production Induces CD8+ T Cell ...anergy was associated with a marked down regulation of IL-2.

Blockade of PD-1 by monoclonal antibodies specific to its ligands (PD-L1 and PD-L2) results in significant enhancement of proliferation and cytokine (gamma interferon [IFN-gamma] and interleukin-2 [IL-2] secretion by tumor-specific CTLs. PD-1 blockade also resulted in down-regulation of intracellular FoxP3 expression by Tregs.

PD-1 blockade seem to augment the proliferation of the CD4+ helper cells.

Now you know why just using Anti-PD1 and or Yervoy as a monotherapy will not have a large response rate. Combinational Therapy is a must if we are to see synergistic responses. IL-2 also plays a major roll in the immune response. IL-2 is added to help maintain fuctionality and survival of the Cytotoxic T Lymphocytes (CTLs) that is despartly needed to eradicate the Melanoma tumors. Our immune system can cure cancer.

 

Jimmy B

 

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

 ~Charles Darwin~

 

Take Care

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Shelby - MRF's picture
Replies 1
Last reply 6/8/2012 - 9:36pm
Replies by: Gene_S

Please join us for a one hour post-ASCO (American Society of Clinical Oncology) teleconference hosted by Dr. Lynn Schuchter and Dr. Georgina Long on June 18th, 2012 at 5:30pm EST.  You will hear 45 minutes of updates on the most current research that was presented at this huge scientific meeting and then have a chance to ask questions.  Registration is required and all of the information you need can be found here:

http://www.melanoma.org/get-involved/post-asco-teleconference 

We hope to have you on the call with us!  A recording of the call will be posted on our website shortly after the call takes place for those of you outside the United States or for those who cannot be on the call at that time.  Have a great weekend!

Shelby - MRF

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rbruce's picture
Replies 28
Last reply 4/14/2013 - 9:45pm

After over a year of nothing but bad news and constant tumor progression, I just met with my Doctor at UCSF who was excited to tell me that I have had over a 30% tumor reduction from the ANTI-PD1 trial I am on.  All of the results out of ASCO last weekend in Chicago about ANTI-PD1 have been very promising and have shown that responders continue to respond.  I am so grateful for the groundbreaking research that is bringing these new immunotherapies to the forefront. I am so thankful for my friends and family that have supported me.  I am eternally thankful to my love, my partner, Lisa who, without her constant love and positive encouragement, I would be lost.  

 
Today is a happy, happy day.  I thank God he continues to give me more time to live each day to the fullest.  I ask for God's blessings in your lives.
 
With love and gratitude,
 
Robert

The circumstances of our lives have as much power as we choose to give them. David McNally

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Erinmay22's picture
Replies 9
Last reply 6/10/2012 - 11:18pm

Ok so I know this topic has been brought up a lot!  I'm about 10 days in to taking it.  I've noticed horrible joint pain (waking me up at night).  As long as I remember to take some anti-inflammatory medicine and get up and move around it seems manageable.  

I am also starting to notice a rash - doesn't seem to really itch yet but I suppose it's only a matter of time.  I'll call my med onc/derm tomorrow to find out what I should do but curious as to what folks did to help manage a rash.  

Thanks!

Erin

www.melanomaandthecity.blogspot.com "people will forget what you said, people will forget what you did, but people will never forget how you made them feel' Maya Angelou

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CORRECTION:

The Melanoma Support Group in San Francisco is offered every Third TUESDAY from 2 pm - 3:30 pm at 2351 Clay St, Suite 137. Registration is required before attending this group. To register for this group or Melanoma Health Lectures call 415-923-3155 or email cpmcchrc@sutterhealth.org.

More information can be found at www.chrcsf.org.

Healthy Regards,

-Community Health Resource Center

Community Health Resource Center... the next step to better health

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Kaley's picture
Replies 3
Last reply 6/8/2012 - 7:04pm
Replies by: Cindy33, Kaley, Janner

I had a superficial malignant melanoma removed 8 years ago. Stage 1B. Clear  SNB and margins. No lymph nodes involved.  Went on to live my life as told to do.  I was here 8 years ago and remember signing up to Janner's group for Stage 1 mel survivors.

This morning I woke up with a tiny raised mole on my neck.  It is dome shaped, perfect  dark color, shiny.  Unbelieveable how quickly this happened. It was not there last night when I went to bed.  Can this be a Nodular Melanoma? Can I have 2 separate melanomas? Is this possible, and has anyone ever heard of someone having 2 types of melanoma?  I'll take any and all advice. Thank you!!!!!!!!

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Jamietk's picture
Replies 4
Last reply 6/8/2012 - 7:14pm
Replies by: Cindy33, Jamietk, deardad

My surgical onc's PA at MDA told me he thought the red dots were prob just hemangiomas but certainly recommended a trip to the derm. Saw the first derm that could get me in, which was not my derm. She was not concerned about the red dots. Said they were just burst blood vessels, prob from injuring my arm (although my surg on PA thought not likely from trauma). In any event, neither are concerned, so I am not either. The derm did find a mole on my left side that she felt was likely mild to moderately dysplastic and wanted to watch it for now and biopsy it at some point. She did not want to biopsy it yet because she did not want to scar me any sooner than necessary. So I said let's go ahead and do that now, I don't like watch and wait if you think ultimately you're wanting a biopsy. She reluctantly agreed, but refused to do a punch. She would only do a shave. I respectfully declined a shave and requested a punch. She went on to tell me she will not do a punch because she is all about preserving the skin and minimizing scarring and punches scar too much. She did agree to set up an appointment for an excision.  She then commented on how bad my wle scar looked for being 7 years out, as well as other biopsies and blemishes on my skin, including my stretch marks. She said I did not have good skin and a punch would scar me too much. It was that point that I no-so-respectfully advised her I was 41 years old, weighed 183 pounds, and have had melanoma. A scar on the left side of my torso that no one but I would see was the least of my concerns. They set me up with an appt to excise it, but 5 minutes down the road I called and cancelled and asked to have my regular derm call me. This woman was just too concerned about the scars and not my health. Granted, maybe a mild to moderately severe mole at this time is not urgent for a biopsy, but she just went on and on about how shaves were so much better cosmetically. That was a waste of 2 hours I'll never get back.

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rrrule32's picture
Replies 4
Last reply 8/9/2012 - 3:42pm

Hello All,

My fiance, Kaitlyn, is 23 years old and has Stage 4 melanoma.  It has moved to her brain.  She starts radiation tomorrow.  They are doing a type of focused radiation, I don't think it's SRS or Gamma Knife or Cyber Knife, but they have this new machine that, as it's giving her whole brain radiation, when it gets to her brain mets, it will stop and dosage will increase.

I'm wondering, people in Kaitlyn's situation, do you have any advice for treatments?  Anything that worked for you?  I'm trying to get our oncologist to give her her last dose of Yervoy.  She had her first 3 doses, and they started working on her body.  Have any of you ever heard of Mannitol?  It's a natural compound that opens up the arteries to the brain and also shrinks the endothelial cells that block foreign agents to the brain.  I'm thinking if Kait were to take Mannitol before receiving any kind of treatment, it would be able to reach the brain.  Anyone else heard of this?  Her oncologist right now doesn't want to give her her last dose of Yervoy because he thinks it could counteract with the radiation.

Anyone ever heard of Hemp Oil from the famous Rick Simpson?  Not hemp seed oil, but hemp oil.

Any advice?  It would be appreciated.

Thank you,

Travis

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youri hasper's picture
Replies 5
Last reply 6/11/2012 - 6:15am

Hello everyone,

My name is Youri and I live in the Netherlands.
My father has been sick for a long time and after succesfull radiation therapies, my fathers melanoma's were stable for over a year. In the pas couple of months the melanoma's started growing again. Radiation and chemo didn't work this time. 

We heard about a new treatment, called R05185426, which possibly would lead to stabilisation, or even shrinking of the melanoma's. In the Netherlands this treatment is still in the experimental stage. An entrance requirement is that the melanoma's above the shoulders are stable. Unfortunately my fathers aren't. Yesterday the doctor told us that my father is excluded from the new treatment. 

My question is, whether in other countries than the Netherland, the treatment can be performed or the new chemo can be optained on the free market. 
We are almost out of hope so if you know anything, please reply, and help us.

With kind regards,

Youri Hasper and family

 

Carpe Diem

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Hello everyone,

My name is Youri and I live in the Netherlands.
My father has been sick for a long time and after succesfull radiation therapies, my fathers melanoma's were stable for over a year. In the pas couple of months the melanoma's started growing again. Radiation and chemo didn't work this time. 

We heard about a new treatment, called R05185426, which possibly would lead to stabilisation, or even shrinking of the melanoma's. In the Netherlands this treatment is still in the experimental stage. An entrance requirement is that the melanoma's above the shoulders are stable. Unfortunately my fathers aren't. Yesterday the doctor told us that my father is excluded from the new treatment. 

My question is, whether in other countries than the Netherland, the treatment can be performed or the new chemo can be optained on the free market. 
We are almost out of hope so if you know anything, please reply, and help us.

With kind regards,

Youri Hasper and family

 

Carpe Diem

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jag's picture
Replies 14
Last reply 6/24/2012 - 3:10pm

I CANNOT THINK OF ANYBODY WHO SURVIVED AUTOLOGOUS T-CELL THERAPY AT THE NIH.

 INVOLVING DR ROSENBERG.  I CAN THINK OF A LOT OF GOOD PEOPLE WHO HAVE PASSED ON DUE TO IT.

IT DOESN'T LOOK ANY ARE LEFT, BUT IF YOU ARE CONSIDERING THIS AS AN OPTION, DON'T DO IT.

Insert Generic Inspirational Motto Here

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Good news for anyone lucky enough to have been in Dr. O'Days care.  He is back practicing at Beverly Hills Cancer Center.  8900 Wilshire Blvd., Beverly Hills, CA.  His phone number is 310) 432-8900.  His email address is SODay@BHCancerCenter.com.

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MeNDave's picture
Replies 14
Last reply 6/18/2012 - 7:21am

Dave had his first set of scans since starting carbo/taxol.  He also had a gamma knife follow up brain MRI.  Brain lesions that were treated are shrinking.  They did identify a 1-2 mm tiny spot on the opposite side which they are choosing to just monitor.

The scans showed improvement in the liver, lungs, spleen, and sub-q's, with the exception of one node in his right axillary which increased slightly.  The liver actually seen an 80% overall reduction in mets, with many not seen anymore.  Same with the spleen.  The down side is that they do see a new lesion in his hip bone/pelvic area.  He also had lesions in his spine, but those appear to be responding to the chemo.  He is having severe pain in his right hand which they believe is due to one of the tumors either in his axillary area or his spine pressing on a nerve.  Pain meds (methadone, oxy, gabapantin, dilaudid) aren't helping, so he is going to start radiation next Monday to the lower spine and armpit to see if it relieves the pain.  His LDH has gone from 8000 when he was in the hospital to 698 - which is just outside the upper limits of normal. 

Given that we KNOW the carbo/taxol is working, he is going to do two more rounds, and then restage.  He could switch to IPI then, or see if he qualifies for one of the anti-pd1 trials. 

All in all, we'll take it!!

Best wishes to all of you,

 

Maria

Don't ever, EVER, give up!

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Anonymous's picture
Anonymous
Replies 9
Last reply 6/8/2012 - 7:27pm
Replies by: Cindy33, Janner, jaredmiller16, natasha, Anonymous, EmilyandMike

After my diagnosis, I was at the derm every three months and now I am at the derm every six.  However, while I am pregnant, he wants to see me every three months. I was there right before delivering my son last week.

I noticed while nursing that I have a new mole under my breast. Lets just say this mole is not a result of sun exposure :) Because of the odd place, I do not think the derm checked this mole in my last visit. Its not visitable on our pictures and I do not remember him looking there..

Needless to say, I am not to worried about it. Its a reddish color, perfectly symmetrical, and has the texture of a skin tag. It looks nothing like what my mel did.

But, I read on a website that any new mole should be reported to the derm immediately regardless of what it looks like. Although this is good advice, I am wondering since I am pretty educated on mel if this is necessary since I go to the derm as much as I do. I get new moles all the time and I would be in his office at least once a month if I followed this advice. I will do whatever do save my life, but then again, I do not want to drive my derm crazy in the meantime. What do you all do?

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Replies by: alpineartist, POW

I like that there is another new option for those considering Interferon...

From the press release: http://www.polynoma.com/docs/PolynomaCommencesPhaseIIIMelanomaVaccineCli...

Polynoma’s melanoma vaccine has an extensive clinical history, having been safely administered to over 650 patients. The current Phase III study of POL 103A has been initiated based on the results of two randomized, placebo-controlled Phase II trials that demonstrated strong efficacy in terms of significantly improved Recurrence-free survival (“RFS”) and overall survival (“OS”). Additionally, POL 103A has exhibited an excellent safety profile.
Dr. Chiplin commented, “POL 103A’s strong safety profile and tolerability have a significant advantage over Interferon, which has limited efficacy and poor tolerability despite its being the current standard of care for resected Stage IIb – III melanoma patients, for whom there are currently no other alternatives.”

FROM CLINICALTRIALS.GOV

http://www.clinicaltrials.gov/ct2/show/NCT01546571?term=POL+103&rank=1

Eligibility:

Ages Eligible for Study:      18 Years to 75 Years
Inclusion Criteria:
Histologically confirmed Stage IIb, IIc, III melanoma
Surgical resection within 90 days of first dosing
Persons with positive sentinel nodes must have a complete lymphadenectomy
ECOG performance status 0 or 1

Exclusion Criteria:
Any prior melanoma treatment other than surgery or regional irradiation
Diagnosis of non-cutaneous melanoma or melanoma with unknown primary origin
Use of biologic response modifiers within 60 days of first dosing
Subjects with history of other malignancy within past 5 years (with exceptions)

Our experience with melanoma: http://emandmichael.wordpress.com/

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