Melanoma International Foundation Exposed!!!! Melanoma ..Jim Breitfeller

In the last couple of days I have been comunicating with a caregiver on the subject of Help! Interleukin-2 or Yervoy?? (lauram)Posted: 1:38:56 pm on 7/15/2011

As I went into my posts I linked some papers that I wrote on the subject matter. It was based on years of research and I thought it had some added value to the subject.
Posted:

"Based on my interpretation of the science, I would do Ipilimumab (Yervoy) first. Make sure you have your ALC (Absolute Lymphocyte count) tested before the trial. If it doubles by week 7, you are most likeely a responder. If not, do the HD-IL-2 regime. Here is a paper that may help you understand the science behind the treatment."




Well, I was in great disbelief that Catherine Poole, the President and Founder of the Melanoma International Foundation had deleted my link and said

Re: Help! Interleukin-2 or Yervoy?? (Catherine Poole)
Posted: 12:24:21 pm on 7/16/2011 Modified: 12:27:43 pm on 7/16/2011


"Jimmy,

I don't think this is based on "the science" but more your opinion on the science. It just hasn't been proved in enough of the population to warrant the recommendation. We must be careful in these assumptions we make. So please do not suggest that here to patients without ample evidence in large segment of the population. We had to edit out your link since it appeared to be a virus within it."


I contunued to post links to clinical data that backed up the science.

Re: Help! Interleukin-2 or Yervoy?? (jimmy_b)
Posted: 8:57:41 pm on 7/16/2011 Modified: Never


Catherine, if you read my intial post: I said"



Based on the science, I would do Ipilimumab (Yervoy) first. Make sure you have your ALC (Absolute Lymphocyte count) tested before the trial. If it doubles by week 7, you are most likeely a responder. If not, do the HD-IL-2 regime. Here is a paper that may help you understand the science behind the treatment."



I am saying the what you are. Do Yervoy first. If you fail, then try HD IL-2. A response from IL-2 can be durable and long lasting (Over 10 Years in some cases)


Patient information:Melanoma treatment; advanced or metastatic melanoma




Author Jeffrey A Sosman, MD



http://www.uptodate.com/contents/patient-information-melanoma-treatment-advanced-or-metastatic-melanoma


MELANOMA TREATMENT

Treatment of metastatic melanoma focuses on:


Shrinking or getting rid of metastases

Preventing the disease from spreading

Keeping you comfortable



In most cases, it is not possible to completely eliminate or cure the cancer. Depending upon where and how big the metastases are, treatment may involve drug treatments, surgery, or radiation therapy.



Drug treatments — There are three main categories of drug treatments:

Immunotherapy – drugs that work with your immune system to stop or slow the growth of cancer cells

Chemotherapy – drugs that stop or slow the growth of cancer cells by interfering with their ability to divide or reproduce themselves

Molecularly targeted therapy- drugs that act to inhibit specific pathways or molecules important to the cancer cells



These drug treatments may be given alone or in combination. Most of these treatments must be given into a vein (intravenously) or injected under the skin, although a few can be given in pill form. Each medication is given over a period of time, sometimes up to several months, depending upon how you respond.



Immunotherapy — Because immunotherapy works differently than chemotherapy, it has different side effects.



Interleukin-2 (IL-2) — IL-2 is a form of immunotherapy that has been found to help some people with metastatic melanoma when given in high doses. In some people treated with high dose IL-2, the benefit can be long-lasting [1-3].



However, high dose IL-2 can cause serious and toxic side effects and it is generally reserved for people who are otherwise healthy (with good heart and lung function).



IL-2 is usually given into a vein three times per day for five days twice per month. Treatment is usually completed while you are in the hospital.


Potential side effects of IL-2 — Potential side effects of high dose IL-2 include low blood pressure, irregular heart rhythms, accumulation of fluid in the lungs, fever, and rarely death.


Ipilimumab — Ipilimumab is a drug that stimulates the body’s immune system to react against the melanoma. This is given once every three weeks for a total of four doses. Treatment with ipilimumab may decrease the extent of your melanoma and help you live longer. But ipilimumab can also cause the body to develop an immune reaction against its own tissues. This can result in a wide range of side effects that may be severe or life threatening. The most important of these include colitis (causing diarrhea, bleeding, or more serious complications), hepatitis, rash or inflammation of the skin, and inflammation of endocrine organs (pituitary, thyroid, or adrenal). If this occurs, you might have to stop the ipilimumab and receive additional treatment for the complications.



If you take this drug, it is important to tell your doctor about any side effects you experience, even mild ones. This will help avoid the more serious complications.



MELANOMA SURVIVAL



Significant progress has been made in the treatment of metastatic melanoma over the past decade. Two drugs that stimulate the immune system, high dose interleukin-2 (IL-2) and ipilimumab, are more effective for controlling metastatic melanoma and allowing some people to live longer. However, both of these forms of immunotherapy can be associated with severe side effects.



In deciding what treatment is right for you, you and your family must consider the risks and benefits of each option according to your values and preferences."



warm regards

Jimmy B
Melanoma Missionary





Advances in Immunotherapy for the Treatment of Metastatic Melanoma


For your Information:

http://www.asco.org/ascov2/Home/Education%20&%20Training/Educational%20Book/PDF%20Files/2011/zds00111000363.PDF



"THE FIRST randomized clinical trial demonstrating an effect on patient survival for the treatment of metastatic melanoma has been recently reported using the immune-stimulating antibody ipilimumab.


This is an important advance in this disease as well as a proof of concept of the ability of immunotherapy to affect the natural course of advanced melanoma. However, the objective tumor response rates are low with CTLA4-blocking antibodies. Response rates up to 50% to 70% have been achieved with an optimized combination of ex vivo, clonally expanded, tumor-infiltrating lymphocytes (TILs) administered after lymphodepleting chemotherapy and followed by high-dose IL-2 administration."

"This provides further evidence of the potential of immunotherapy for the treatment of melanoma."

Dr. Antonio Ribas 2011


My Therory, is that instead of clonally expanding the (TILs) tumor-infiltrating lymphocytes ex vivo, and not depleting the Tregs, WE are doing it all in vivo (Inside the Body). The reason we skip the Lymphodepleting is that the CD4-T-cell in need to secrete just the right amount of IL-2 to activate the and prime the CD-8 T-cells. The High dose IL-2 is there to muture the CD8- T-cells into Cytotoxic T lymphocytes (CTLs).

I know there are skeptics out there, but we need to read the research papers that are cutting edge to make any progress. Why is Dr. Steven Rosenberg using IL-2 in his ACT therapy?

You need to think outside the box and not reject things that you don't understand.
best regards

Again Catherine poole responded:

Again, Jimmy, we don't believe the science until it is proven in many individuals. Hundreds of patients should show these results before it is proven fact and enough to base an opinion about. Rosenberg has been using IL2 for 20 years or more, it is his drug of choice. Why? I'm not certain, but I've not been impressed by the results of research at NCI in melanoma. So I imagine there is funding from the industry for this particular drug to be used. And they need funding desperately for melanoma at NCI, it is not a priority. I would just suggest that our recommendations be based on large studies here and so far Yervoy has more promise than IL2 and is far less debilitating..

Catherine M. Poole, President/Founder

Melanoma International Foundation


Again I responded with :

Re: Help! Interleukin-2 or Yervoy?? (jimmy_b)
Posted: 9:58:59 pm on 7/16/2011 Modified: Never


Ipilimumab in Combination with IL-2

Author: Jeffrey Weber, M.D., Ph.D., H. Lee Moffitt Cancer Center



July of 2008



Thirty-six patients with stage IV metastatic melanoma were treated with ipilimumab at doses in the range of 0.1–3mg/kg every 3 weeks combined with IL-2 at 720,000 IU/kg every 8 hours to a maximum of 15 doses [20]. There was an ORR of 22%, with three patients having a CR and five patients having a PR. Five of the responses occurred among the 24 patients treated with ipilimumab at 3 mg/kg, and one each occurred in those treated with 0.3, 1, and 2 mg/kg. Six of the eight responders had ongoing responses at follow-up of 11–19 months. The 22% ORR reflects an additive rather than a synergistic effect for these two agents, although durable responses were demonstrated.



Based on the initial experience with ipilimumab in combination with chemotherapy or IL-2, additive effects have been seen, as opposed to synergy. However, the results from these trials suggest that combination therapy with ipilimumab may play an important role in the treatment of metastatic melanoma; larger trials are required, including an ongoing phase III trial of ipilimumab plus dacarbazine compared with dacarbazine alone in frontline therapy, before further conclusions can be drawn.

http://theoncologist.alphamedpress.org/content/13/suppl_4/16.full

Jimmy B
Melanoma Missionary


Re: Help! Interleukin-2 or Yervoy?? (jimmy_b)
Posted: 10:35:56 pm on 7/16/2011

Cytotoxic T lymphocyte-associated antigen 4 blockade with ipilimumab: Long-term follow-up of 179 patients with metastatic melanoma 2010 ASCO Annual Meeting



Abstract No:8544

Citation:
J Clin Oncol 28:15s, 2010 (suppl; abstr 8544)


Author(s):


P. A. Prieto, J. C. Yang, R. M. Sherry, M. S. Hughes, U. S. Kammula, D. E. White, C. L. Levy, S. A. Rosenberg, G. Q. Phan; Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; National Cancer Institute, National Institutes of Health, Bethesda, MD; National Cancer Institute, Bethesda, MD; Surgery Branch, National Cancer Institute, Bethesda, MD



Abstract:


Background: We have previously shown objective clinical responses in patients with metastatic melanoma treated with CTLA-4 blockade using ipilimumab. We have treated 179 patients in 3 separate clinical trials and now have long-term follow-up to evaluate the durability and unique features of this immunotherapy. Methods: A total of 179 patients with metastatic melanoma were treated in 3 trials: In Protocol 1, 56 patients received ipilimumab with gp100 peptide vaccines. In Protocol 2, 36 patients received ipilimumab with high-dose interleukin-2 (IL-2). In Protocol 3, 87 patients received intra-patient dose escalation of ipilimumab and were randomized to receive gp100 peptides. We have updated and analyzed the follow-up and survival data for these trials. Results: With median follow-up for Protocol 1, 2, and 3 being 80, 71, and 60 months, median survival was 15, 16, and 13 months, respectively. Objective tumor regression was 12% for Protocol 1, 25% for Protocol 2, and 21% for Protocol 3. Patients in Protocol 2 had a 17% complete response rate (6 patients: 77+, 74+, 72+, 71+, 71+, and 69+ months), as compared to 7% in Protocol 1 (4 patients: 82+, 81+, 79+, and 66+ months) and 8% in Protocol 3 (5 patients: 64+, 63+, 62+, 60+, and 55+ months); all complete responses are ongoing. Many patients who eventually became complete responders had continual tumor shrinkage after stopping therapy. Conclusions: CTLA-4 blockade with ipilimumab can achieve durable objective tumor regression in patients with metastatic melanoma. The combination of ipilimumab and IL-2 appears to have an increased complete response rate, although this needs to be tested in a prospective randomized trial. This report represents the largest single-institution experience with the longest follow-up for this agent; our results support its role as a viable treatment option for patients with metastatic melanoma.



Catherine My Theory does have Merit. It is the Science backup with some clinical Data.



Lets Think OUTSIDE THE BOX!!!!



best regards

Jimmy B
Melanoma Missionary


Re: Help! Interleukin-2 or Yervoy?? (Catherine Poole)
Posted: 7:10:37 am on 7/17/2011 Modified: 7:15:36 am on 7/17/2011


This just isn't the place for you to post all of this. Just give the citations. As I mentioned in the other response to your post, you are not a peer reviewed credentialled medical researcher. We always think outside the box here but we also keep in mind the validity of research and whether large numbers of people benefitted. We also talk in terms that people can understand easily. You are a missionary by your self description, bent on a mission and we are navigators exploring all options.


Catherine M. Poole, President/Founder



Melanoma International Foundation


The MIF Website and Forums are designed for educational purposes only and are not engaged in rendering medical advice or professional services. The information provided through this Website should not be used for diagnosing or treating a health problem or a disease. It is not a substitute for professional care. If you have or suspect you may have a health problem, you should consult your health care provider.



Re: Help! Interleukin-2 or Yervoy?? (Catherine Poole)
Posted: 7:12:02 am on 7/17/2011 Modified: Never


This just isn't the place for you to post all of this. Just give the citations. As I mentioned in the other response to your post, you are not a peer reviewed medical researcher.



Catherine M. Poole, President/Founder



Melanoma International Foundation



The MIF Website and Forums are designed for educational purposes only and are not engaged in rendering medical advice or professional services. The information provided through this Website should not be used for diagnosing or treating a health problem or a disease. It is not a substitute for professional care. If you have or suspect you may have a health problem, you should consult your health care provider.



Re: Help! Interleukin-2 or Yervoy?? (jimmy_b)
Posted: 8:21:51 am on 7/17/2011 Modified: Never


Catherine, What credentials do you have may I ask. How many patents do you have. I rest my case.



You are blinded by your own lack of understanding.





Jimmy B




Re: Help! Interleukin-2 or Yervoy?? (Catherine Poole)
Posted: 7:10:37 am on 7/17/2011 Modified: 10:53:34 am on 7/17/2011


This just isn't the place for you to post all of this and we don't like our forum to have the negativity that you exhibit. Just give the citations as you are taking space away from others. As I mentioned in the other response to your post, you are not a peer reviewed credentialed medical researcher. I have never claimed to be either. I rely on the opinion of medical experts who are credentialed and peer reviewed in their work in melanoma research from the outstanding cancer centers who specialize in melanoma. We always think outside the box here but we also keep in mind the validity of research and whether large numbers of people benefitted. I know you are promoting what worked for you and then backing it with research you have found that could be interpreted in a different light. We also talk in terms that people can understand easily. You are a missionary by your self description, bent on specific therapy mission and we are navigators exploring all options. You have your own website for that purpose and we'd appreciate you keeping your lengthy opinions there.


Catherine M. Poole, President/Founder



Melanoma International Foundation




This forum is moderated by specialists in melanoma, primarily by volunteer dermatologists and oncologists on a weekly basis. In addition, Catherine Poole, President and Founder of the Melanoma International Foundation, a melanoma survivor, and patient navigator for 20 years and co-author with DuPont Guerry, MD a melanoma expert, of Melanoma, Prevention, Detection and Treatment, (Yale University Press: 2005) monitors this site many times daily. Information on


Re: Help! Interleukin-2 or Yervoy?? (jimmy_b)Posted: 11:33:12 am on 7/17/2011
Laura,



Re: Help! Interleukin-2 or Yervoy?? (jimmy_b)
Posted: 11:33:12 am on 7/17/2011 Modified: Never


Laura,

Thanks, as you can see, Catherine Poole is pushing her own agenda and has delete my entries.



What happen to the Freedom of Speech act?



This forum is NOT moderated by specialists in melanoma, primarily by volunteer dermatologists and oncologists on a weekly basis. This is very Sad.


Jimmy B
Melanoma Missionary

If you go to Melanoma International Foundation for advice, You may not be getting the whole picture.

I was not pushing my theory, I was giving my opinion. As for Catherine M. Poole,
who is sending out The Negativity.

"We don't like our forum to have the negativity that you exhibit."
~Catherine M. Poole_

You be the judge


I don't delete links and entries or comments on my web blog. Everyone is entitled to their opinoin.


“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,
Jimmy B

Why Should We Believe That There Was Even a Shortage of Ipilimumab?Melanoma ..Jim Breitfeller

On June 11, 2007, BMS agreed to plead guilty and pay a $1 million criminal fine for misleading the government about the Plavix patent deal. BMS paid the maximum fine permitted by statute for committing two violations under the federal False Statements Act."

They mislead Government officials so why would they tell us the Patients, the truth about the shortage?

April 25 2008

Medarex and Bristol-Myers Squibb Joint Statement on Submission Status of Ipilimumab

PRINCETON, N.J., April 25 2008 /PRNewswire-FirstCall/ -- Medarex, Inc.
(Nasdaq: MEDX) and Bristol-Myers Squibb Company (NYSE: BMY) today announced that, after meeting with the U.S. Food and Drug Administration (FDA), the companies will delay the Biologics License Application (BLA) submission for ipilimumab, an investigational immunotherapy for patients with advanced metastatic melanoma. The FDA has requested additional overall survival (OS)data to further demonstrate the benefit of ipilimumab. Revised timelines are under development, but a BLA for ipilimumab will not be submitted to the FDA in 2008.

As far as my research to date(10-22-2009), BMS/Medarex has not file a BLA with the FDA.


On September 12 2008 they closed the compassionate use for Ipilimumab

Your email was forwarded to us by CBER (this IND resides in the Center for Drugs Evaluation and Research). We have contacted BMS to check into the availability of ipilimumab and here is the information that BMS provided to us.

"To ensure treatment is not interrupted for patients currently receiving ipilimumab and to provide ongoing supply to the registrational program, Bristol-Myers Squibb and Medarex have suspended enrollment of new patients into the compassionate use program, single patient exemptions and initiation of some non-registrational trials effective September 12, 2008.

Bristol-Myers Squibb and Medarex are working to manage the supply issue and may be able to re-open compassionate use in the future.

The companies are committed to providing uninterrupted treatment to patients who initiate therapy with ipilimumab. Therefore, if and when the compassionate use program reopens, it will be at such time when continuous and unconstrained supply is available."

Please let us know if you have any questions.

Sincerely,
CDER Drug Shortage Team


It Takes about a month to make a batch of monoclonal antibodies. By the time the batch is tested and packaged and approved, let us allow another two months. So in a year you should be able to make 3 to 4 batches.


Melanoma Treatment Information - Updated 09.10.09

"Ipilimumab which ASCO reported some promising results had been widely available in compassionate use trials across the county until a shortage halted the studies. Bristol Myers Squibb, is now manufacturing the drug again and there are a few small “pharmacokinetic” trials to prove the agent is the same as the previous one used in trials. Most of these trials already have waiting lists, but it may be worth checking out. Screening started August 4th and you can find the locations on www.clinicaltrials.gov."

Source:https://www.z2systems.com/np/clients/mif/news.jsp?news=381

Melanoma International Foundation


Well come to find out that BMS/Medarex is opening up new clinical trials with Ipilimumab and continue to keep the compassionate use trial closed. How ethical is that?

When big pharma is involved in clinical development, it usually means large-scale clinical trials with patients and multiple sites.

Here are the trials:

Study of Ipilimumab and Dasatinib Combination Therapy in Patients With Chronic or Accelerated Chronic Myeloid Leukemia
Start Date: August 2009
Estimated Study Completion Date: Feb 2011
Estimated Enrollment: 30
ClinicalTrials.gov Identifier: NCT00732186

Ipilimumab +/- Vaccine Therapy in Treating Patients With Locally Advanced, Unresectable or Metastatic Pancreatic Cancer
Start Date: February 2009
Estimated Study Completion Date: Feb 2013
Estimated Enrollment: 30
ClinicalTrials.gov Identifier: NCT00836407

Bevacizumab Plus Ipilimumab in Patients With Unresectable Stage III or IV Melanoma
Start Date: February 2009
Estimated Study Completion Date: Feb 2011
Estimated Enrollment: 33
ClinicalTrials.gov Identifier: NCT00790010

Laboratory-Treated T Cells With or Without Ipilimumab in Treating Patients With Metastatic Melanoma
Start Date: February 2009
Estimated Study Completion Date: Feb 2011
Estimated Enrollment: 30
ClinicalTrials.gov Identifier: NCT00871481

Study of Immunotherapy to Treat Advanced Prostate Cancer
Start Date: May 2009
Estimated Study Completion Date: December 2012
Estimated Enrollment: 800
ClinicalTrials.gov Identifier: NCT00861614

Further study details as provided by Bristol-Myers Squibb:


These are all trials that were started after the halting of the compassionate Use. Bristol-Meyer Squibb thinks we the Melanoma Patients are expendable so they continued there quest to seek out new uses for the Drug.

Get a bigger bang for the buck.

They already know it works well with Melanoma, so why not find other uses.

Base on my calculation, 923 late stage Melanoma Patients were denied the drug while Bristol–Meyer Squibb continued to apply and start up new trials.



Bristol-Meyer Squibb Quote:

“What sets us apart? We believe it's our commitment to patients with serious diseases, our focus on finding innovative medicines that combat those diseases, and our dedication to extending and enhancing human life.”

All Lip Service!!!!!!

“Jim, thank you so much for your efforts. My father passed away this past March. He was also scheduled to start the ipi trial last year and found out the Saturday before he was to go in that the compassionate use trial was suspended. He developed 3 mets in his brain by Thanksgiving. The ipi trials with brain mets were closed to new patients by then. I've spent countless hours and days frustrated and angry, unable to express or figure out what you have with BMS and wanting to take some sort of action. I also sent letters, made phone calls, etc. One day, someone will be able to stop these drug companies from playing with our lives. Please keep me posted in your findings.”



Update on Ipilimumab

Ipilimumab is not back yet. Patients are not being encouraged to wait for Ipilimumab to become available for now. The only Ipilimumab melanoma trials currently enrolling new patients in the US are the brain metastases trial (CA-184042) and the phase 3 adjuvant trial (CA-184029) because the supply for those trials was protected in advance. Bristol Myers Squibb is working diligently to overcome the drug shortage, but can’t guarantee a time that it will return to the compassionate use setting.

Source: Melanoma International Foundation:
https://www.zsystems.com/np/clients/mif/news.jsp?news=376


Melanoma International Foundation



Response from BMS as of 10-21-2009

“Regarding compassionate use, as you are aware, the rate of enrollment in the compassionate use program for ipilimumab was greater than anticipated with 30 to 40 percent of patients continuing on therapy beyond the initial induction schedule. This demand depleted drug supply at a faster rate than anticipated. Bristol-Myers Squibb had to suspend enrollment of new patients into the compassionate use program and single patient exemptions to ensure treatment is not interrupted for patients currently receiving ipilimumab and to provide supply for ongoing clinical studies.

We are working through the manufacturing and testing process, and continue to carefully manage the supply to enable the potential re-opening of compassionate use at the earliest possible time and when continuous supply is available.

Bristol-Myers Squibb remains committed to the development of ipilimumab and to addressing the great unmet medical need for patients with metastatic melanoma.”

As you can read, BMS is not even acknowledging that they even produced other batches.They are hiding the fact that they are back online. Their communication skills with the public/patients are NIL. Instead they are starting new protocols with Ipilimumab. Where is the FDA in al of this? Who is watching the hen house?

When I searched for drug shortages on the FDA website, Ipilimumab did not show up.

What is going on?

We the Patients deserve better, We are the ones who are taking all the risk. We should have some control in this process.

We the Patients have had to hear it from second-hand sources like the Melanoma International Foundation and Melanoma Research Foundation. I don’t believe that their ad advertisers (The Ogilvy Group Inc) can repair the public’s trust in this company. They have major issues.

This Month will be the anniversary of the discovery of Anti-CTLA-4 antibodies, celebrating ten years in the making of the drug. This is way to long for a drug to come to market. It usually takes 8.7 years for monoclonal antibodies. So what gives?

I hope see some dialog started between the patients and BMS. BMS needs somehow to regain the public's trust.

I am under the impression that greed and power-play is mixed in all of this. It all has to do with the STRING OF PEARLS intiative.



How Drugs are Developed and Approved by the FDA?

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/default.htm#


How Drugs are Developed and Approved by the FDA



Take Care,

Jimmy B