› Forums › General Melanoma Community › Testing for NY-ESO-1 Expression and its recent correlation to the efficacy of Ippilumimab
- This topic has 24 replies, 5 voices, and was last updated 12 years, 6 months ago by AlisonC.
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- October 20, 2011 at 5:54 am
I am new to the MRF and constantly up late at night searching for any type of enlightenment and encouragement in my husband's battle with this disease. But alas!!!! In all of my research over the past two and a half months, I have learned so much but can still seem to find no clear resolution as to the most effective adjuvant protocol. My husband first noticed a lesion in the anterior submandibular area (near his jawline) in Level II of his cervical region (so upper neck at jawline) in 2003.
I am new to the MRF and constantly up late at night searching for any type of enlightenment and encouragement in my husband's battle with this disease. But alas!!!! In all of my research over the past two and a half months, I have learned so much but can still seem to find no clear resolution as to the most effective adjuvant protocol. My husband first noticed a lesion in the anterior submandibular area (near his jawline) in Level II of his cervical region (so upper neck at jawline) in 2003. Due to a primary care physician's casual dismissal of the lesion in the Fall of that year, he was not officially diagnosed by a dermatologist with melanoma until March 2007 after obtaining the results of a punch biopsy. At which time he was diagnosed as Stage1b – with lentigo maligna melanoma in a non ulcerated form, possessing a Breslow depth of 1.35mm, a mitotic rate of 2, and finally a Clark Level of IV. He received a WLE and a SLN biopsy later in March 2007. He received NED on the two nodes thought to be the sentinel draining nodes. After a follow up resection, he was confirmed to have clear margins, which exceeded the recommended 1cm. Fast forward to July of 2011 when he noticed a slight enlargement of a lymph node within a few centimeters of his original tumor site. After a CAT scan and FNA, we learned that his melanoma had returned consequently escalating his stage to 3b at minimum. He proceeded with a modified radical neck dissection in August to remove 39 nodes in Levels I through V and is recovering nicely. In the interim since the surgery and after numerous requests for ALL of his records including PATHOLOGY, we learned through the reports of the lymphoscintography procedure from the SLN biopsy that this node was most likely left in since the 2007 surgery as the background counts reported were much higher than the recommended 1/3 ratio of the initial in vivo count. Ironically the node that he discovered was in the intraparotid area, which we later learned was cited on the report as a problem area from which to extract nodes. THANK THE GOOD LORD!!! Only the one palpable node came back positive with the pathologist reporting 60% of the node to contain melanoma and no extracapsular involvement was confirmed. We are considering an ippi trial but I have some questions as to the efficacy of the ippi if one tests positive for a preexisting antibody to the NY-ESO-1 antigen. Given that my husband is a testicular cancer survivor of 20 years, I was particularly curious as this antigen is a cancer testis antigen and expresses in over 50% of cancerous tissues but not in normal tissues other than the testis in fetal stages. Given that his bout with testicular cancer might have resulted in a subsequent antibody development coupled with the recent discovery of a reduced effectiveness of Ippi on those patients possessing this antibody, I am itching to determine if he is expressing this antigen. If not, then has he developed the antibody? We are reluctant to proceed with the Ippi given its toxicities if his benefit will most likely be reduced. Has anyone here been tested for this expression and where? If so, did you proceed with the Ippi and was it effective? I have seen some research of late (literally only published on Oct. 4 2011) that states that there is some question as to the degree of efficacy on Ippi patients who possess this antibody prior to the start of the drug. My inclination is that these may be some of the "late responders"..just a notion?. It is interesting to note the tumor antigen specific correlations with all of the current treatments available – Ippi, IFN a, and others. Also, I have read of a tumor specific expression that correlates to the success ratio of Interferon. Has anyone had this test run? Has anyone ventured "down under" to try the current vaccine trials by Oncovex? All feedback is welcome!!!
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- October 20, 2011 at 7:21 am
My Mother completed Yervoy in July and tested after for a clinical trial CDX-1401 at Mount Sinai in Miami Beach. It is a Phase 1/11, Study of CDX-1401 in Patients with Malignancies known to express NY-ESO-1. However, she does not have the expression. She is Braf and C-Kit negative as well. I know that this trial is also going in Hunterville, North Carolina:
Carolina BioOncology Institute
704-947-6599 Ext. 103: Jahleen Byers [email protected] / John Powderly, MD Principle Investigator
Maybe you can contact them for more information in regards to NY-ESO-1. My Mother has a very rare melanoma, Mucosal Melanoma. I hope this information can help you.
Warm regards to you and yourhusband.
Wendy
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- October 20, 2011 at 5:49 pm
Thanks for the information Wendy!! How was your Mother's response to Yervoy? My husband is negative for Braf as well. Since he does not have the mucosal variety, but rather lentigo maligna melanoma he would most likely not be C-kit either. Since my husband has had the tumor in his lymph node removed, he is technically NED so he is not eligible for the clinical trial on the CDX-1401. I did call the Huntersville Clinic to see if they are able to run the test to determine the expression but apparently they are not equipped with that test. They send all of their cartridges off. I was just hoping to find a laboratory locally that could run the test to determine the NY-ESO-1 expression as well as its subsequent antibody expression if such should exist. CMC and Celligent are not equipped to run that test either. I will keep searching. I hope your Mom is doing well. Did she have positive results since her Yervoy completion? I will keep her in my thoughts and prayers!!
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- October 20, 2011 at 5:49 pm
Thanks for the information Wendy!! How was your Mother's response to Yervoy? My husband is negative for Braf as well. Since he does not have the mucosal variety, but rather lentigo maligna melanoma he would most likely not be C-kit either. Since my husband has had the tumor in his lymph node removed, he is technically NED so he is not eligible for the clinical trial on the CDX-1401. I did call the Huntersville Clinic to see if they are able to run the test to determine the expression but apparently they are not equipped with that test. They send all of their cartridges off. I was just hoping to find a laboratory locally that could run the test to determine the NY-ESO-1 expression as well as its subsequent antibody expression if such should exist. CMC and Celligent are not equipped to run that test either. I will keep searching. I hope your Mom is doing well. Did she have positive results since her Yervoy completion? I will keep her in my thoughts and prayers!!
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- October 20, 2011 at 5:49 pm
Thanks for the information Wendy!! How was your Mother's response to Yervoy? My husband is negative for Braf as well. Since he does not have the mucosal variety, but rather lentigo maligna melanoma he would most likely not be C-kit either. Since my husband has had the tumor in his lymph node removed, he is technically NED so he is not eligible for the clinical trial on the CDX-1401. I did call the Huntersville Clinic to see if they are able to run the test to determine the expression but apparently they are not equipped with that test. They send all of their cartridges off. I was just hoping to find a laboratory locally that could run the test to determine the NY-ESO-1 expression as well as its subsequent antibody expression if such should exist. CMC and Celligent are not equipped to run that test either. I will keep searching. I hope your Mom is doing well. Did she have positive results since her Yervoy completion? I will keep her in my thoughts and prayers!!
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- October 20, 2011 at 5:58 pm
Wendy, thanks so much for the information. I hope your Mom is doing better and she has responded to the Yervoy. My husband is also BRAF negative and I am doubtful that he would test for the C-kit expression since he has a lentigo maligna variety as opposed to the mucosal subtype. Since my husband's intranodal tumor has been surgically resected, he is not a candidate for the CDX-1401 trial as we are primarily searching for the most effective adjuvant therapy. I did call the laboratory in Huntersville to arrange a test to determine the NY-ESO-1 expression and possibly that of its antibody should it exist. Unfortunately, they were unable to perform this test. Jahleen indicated that they send all of their tests off to determine these results. BUT I really appreciate the lead. I will keep searching for a local facility that could provide this test. I will keep your Mom in my thoughts and prayers!! How is she doing since her July completion of Yervoy? I hope well!! Thanks again!!
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- October 20, 2011 at 5:58 pm
Wendy, thanks so much for the information. I hope your Mom is doing better and she has responded to the Yervoy. My husband is also BRAF negative and I am doubtful that he would test for the C-kit expression since he has a lentigo maligna variety as opposed to the mucosal subtype. Since my husband's intranodal tumor has been surgically resected, he is not a candidate for the CDX-1401 trial as we are primarily searching for the most effective adjuvant therapy. I did call the laboratory in Huntersville to arrange a test to determine the NY-ESO-1 expression and possibly that of its antibody should it exist. Unfortunately, they were unable to perform this test. Jahleen indicated that they send all of their tests off to determine these results. BUT I really appreciate the lead. I will keep searching for a local facility that could provide this test. I will keep your Mom in my thoughts and prayers!! How is she doing since her July completion of Yervoy? I hope well!! Thanks again!!
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- October 20, 2011 at 5:58 pm
Wendy, thanks so much for the information. I hope your Mom is doing better and she has responded to the Yervoy. My husband is also BRAF negative and I am doubtful that he would test for the C-kit expression since he has a lentigo maligna variety as opposed to the mucosal subtype. Since my husband's intranodal tumor has been surgically resected, he is not a candidate for the CDX-1401 trial as we are primarily searching for the most effective adjuvant therapy. I did call the laboratory in Huntersville to arrange a test to determine the NY-ESO-1 expression and possibly that of its antibody should it exist. Unfortunately, they were unable to perform this test. Jahleen indicated that they send all of their tests off to determine these results. BUT I really appreciate the lead. I will keep searching for a local facility that could provide this test. I will keep your Mom in my thoughts and prayers!! How is she doing since her July completion of Yervoy? I hope well!! Thanks again!!
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- October 20, 2011 at 7:21 am
My Mother completed Yervoy in July and tested after for a clinical trial CDX-1401 at Mount Sinai in Miami Beach. It is a Phase 1/11, Study of CDX-1401 in Patients with Malignancies known to express NY-ESO-1. However, she does not have the expression. She is Braf and C-Kit negative as well. I know that this trial is also going in Hunterville, North Carolina:
Carolina BioOncology Institute
704-947-6599 Ext. 103: Jahleen Byers [email protected] / John Powderly, MD Principle Investigator
Maybe you can contact them for more information in regards to NY-ESO-1. My Mother has a very rare melanoma, Mucosal Melanoma. I hope this information can help you.
Warm regards to you and yourhusband.
Wendy
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- October 20, 2011 at 7:21 am
My Mother completed Yervoy in July and tested after for a clinical trial CDX-1401 at Mount Sinai in Miami Beach. It is a Phase 1/11, Study of CDX-1401 in Patients with Malignancies known to express NY-ESO-1. However, she does not have the expression. She is Braf and C-Kit negative as well. I know that this trial is also going in Hunterville, North Carolina:
Carolina BioOncology Institute
704-947-6599 Ext. 103: Jahleen Byers [email protected] / John Powderly, MD Principle Investigator
Maybe you can contact them for more information in regards to NY-ESO-1. My Mother has a very rare melanoma, Mucosal Melanoma. I hope this information can help you.
Warm regards to you and yourhusband.
Wendy
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- October 20, 2011 at 12:40 pm
PBJ, welcome to our forum. Testing for NY-ESO-1 is unusual, but I think that some people here have had the test. However, I don't know if any have had the test in relation to the possible efficacy of ipi.
I would just like to make some comments about treatments in general. Although ipi (now called Yervoy) is a valuable new treatment, neither it nor any current therapy is a guaranteed cure for metastatic melanoma. It is also very difficult to predict who will respond to what treatment.
Research is advancing quickly, but this cancer is usually able to outsmart the effects anything that we have. However, a small number of people have been able to achieve NED (no evidence of disease) for a very long time.
These are some treatments that show promise and are worth looking at, depending on eligibility criteria and availability: GM-CSF (Leukine) and surgery when needed, Yervoy, BRAF and similar inhibitors, IL-2, and anti PD-1 (MDX-1106). However, I feel that TIL treatment (adoptive cell therapy) is the option that may give suitable patients the best chance of achieving a durable remission.
Hope this helps.
Frank from Australia
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- October 20, 2011 at 6:14 pm
Yes, Frank!! I agree with you on the adoptive cell transfer theories as well as the dendritic vaccines!! My husband is BRAF negative so Vemurafenib is not an option. I too have read extensively about the granulyte macrophage colony stimulating factor and its consequence to the cytotoxic t cells in melanoma. I feel this is very promising, but thus far I have not been able to locate a clinical trial for Stage 3b patients in the U.S. I know ECOG conducted an 800+ patient trial to determine the efficacy of GM-CSF as an adjuvant therapy but they are awaiting results. Do you know of any trials that are open in Australia? Or a website that I can search for trials in Australia? Interestingly enough, I know you must be so proud of your fellow Aussies as it is my opinion that your docs/researchers are leading the way in discovering viable antigen tumor specific therapies for this disease! I like you am hesitant to believe that one drug that signals only one pathway can slow down the progression of a disease that is known to link directly to the immune system and its numerous signalling pathways. Also, we are yet to see the long term autologous effects of the stimulation of the apoptotic phase of the cell division. I really appreciate your reply as you seem to be a kindred spirit as a "research junkie"!! Please share any other theories that you might have as I know you have been at this much longer than I. Thanks!!
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- October 20, 2011 at 6:14 pm
Yes, Frank!! I agree with you on the adoptive cell transfer theories as well as the dendritic vaccines!! My husband is BRAF negative so Vemurafenib is not an option. I too have read extensively about the granulyte macrophage colony stimulating factor and its consequence to the cytotoxic t cells in melanoma. I feel this is very promising, but thus far I have not been able to locate a clinical trial for Stage 3b patients in the U.S. I know ECOG conducted an 800+ patient trial to determine the efficacy of GM-CSF as an adjuvant therapy but they are awaiting results. Do you know of any trials that are open in Australia? Or a website that I can search for trials in Australia? Interestingly enough, I know you must be so proud of your fellow Aussies as it is my opinion that your docs/researchers are leading the way in discovering viable antigen tumor specific therapies for this disease! I like you am hesitant to believe that one drug that signals only one pathway can slow down the progression of a disease that is known to link directly to the immune system and its numerous signalling pathways. Also, we are yet to see the long term autologous effects of the stimulation of the apoptotic phase of the cell division. I really appreciate your reply as you seem to be a kindred spirit as a "research junkie"!! Please share any other theories that you might have as I know you have been at this much longer than I. Thanks!!
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- October 20, 2011 at 6:37 pm
The results with the GMCSF trial info came out last years ASCO. The results did not show any significance showing the results. There were 4 arms. 2 had the dendritic vaccines and you had to be hla 0201. The other arms included just the gmcsf or a placebo. (I was in part of that trial and once I recurred they did disclose my info)
There are still some Doctors out there prescribing off label but isn't heard about as much. For quite a while it was on the board talked about lately but with the last results much quieter. As with all drugs it does happen for someone but is it just that the person would have done well or did it actually work.
I do think they are now trying the GMCSF with a combo with Ippi in a few trials in the New York or Mass area. This is for those that have currently active disease.
Linda
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- October 20, 2011 at 6:37 pm
The results with the GMCSF trial info came out last years ASCO. The results did not show any significance showing the results. There were 4 arms. 2 had the dendritic vaccines and you had to be hla 0201. The other arms included just the gmcsf or a placebo. (I was in part of that trial and once I recurred they did disclose my info)
There are still some Doctors out there prescribing off label but isn't heard about as much. For quite a while it was on the board talked about lately but with the last results much quieter. As with all drugs it does happen for someone but is it just that the person would have done well or did it actually work.
I do think they are now trying the GMCSF with a combo with Ippi in a few trials in the New York or Mass area. This is for those that have currently active disease.
Linda
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- October 20, 2011 at 6:37 pm
The results with the GMCSF trial info came out last years ASCO. The results did not show any significance showing the results. There were 4 arms. 2 had the dendritic vaccines and you had to be hla 0201. The other arms included just the gmcsf or a placebo. (I was in part of that trial and once I recurred they did disclose my info)
There are still some Doctors out there prescribing off label but isn't heard about as much. For quite a while it was on the board talked about lately but with the last results much quieter. As with all drugs it does happen for someone but is it just that the person would have done well or did it actually work.
I do think they are now trying the GMCSF with a combo with Ippi in a few trials in the New York or Mass area. This is for those that have currently active disease.
Linda
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- October 21, 2011 at 4:01 am
As far as I know, the most comprehensive site for all clinical trials around the world
is http://www.clinicaltrials.gov. I doubt if there are any better websites available.Here are the trials that include GM-CSF at the moment:
http://www.clinicaltrials.gov/ct2/results?term=GM-CSF+melanoma+&recr=Open&rslt=&type=&cond=&intr=&outc=&lead=&spons=&id=&state1=&cntry1=&state2=&cntry2=&state3=&cntry3=&locn=&gndr=&rcv_s=&rcv_e=&lup_s=&lup_e=Although melanoma vaccines have a lot of potential in theory, there has been little in
the way of positive results so far. However, the following article is encouraging:
http://www.sciencedaily.com/releases/2011/06/110602091834.htmI think that it is important for patients to have definite treatment plans in mind
with options that may be possible. So, if one treatment doesn't work I think that it is
wise to have a plan B, plan C, etc.I started reading about melanoma in early 2007, and there have been a lot of
advancements since then. However, the big problem is that melanoma is much more devious
than we imagine as it seems to actively overcome nearly all attempts to stop metastasis.
I feel that stopping metastasis is the key to treatment success.Thanks for your kind words.
Frank from Australia
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- October 21, 2011 at 4:01 am
As far as I know, the most comprehensive site for all clinical trials around the world
is http://www.clinicaltrials.gov. I doubt if there are any better websites available.Here are the trials that include GM-CSF at the moment:
http://www.clinicaltrials.gov/ct2/results?term=GM-CSF+melanoma+&recr=Open&rslt=&type=&cond=&intr=&outc=&lead=&spons=&id=&state1=&cntry1=&state2=&cntry2=&state3=&cntry3=&locn=&gndr=&rcv_s=&rcv_e=&lup_s=&lup_e=Although melanoma vaccines have a lot of potential in theory, there has been little in
the way of positive results so far. However, the following article is encouraging:
http://www.sciencedaily.com/releases/2011/06/110602091834.htmI think that it is important for patients to have definite treatment plans in mind
with options that may be possible. So, if one treatment doesn't work I think that it is
wise to have a plan B, plan C, etc.I started reading about melanoma in early 2007, and there have been a lot of
advancements since then. However, the big problem is that melanoma is much more devious
than we imagine as it seems to actively overcome nearly all attempts to stop metastasis.
I feel that stopping metastasis is the key to treatment success.Thanks for your kind words.
Frank from Australia
-
- October 21, 2011 at 4:01 am
As far as I know, the most comprehensive site for all clinical trials around the world
is http://www.clinicaltrials.gov. I doubt if there are any better websites available.Here are the trials that include GM-CSF at the moment:
http://www.clinicaltrials.gov/ct2/results?term=GM-CSF+melanoma+&recr=Open&rslt=&type=&cond=&intr=&outc=&lead=&spons=&id=&state1=&cntry1=&state2=&cntry2=&state3=&cntry3=&locn=&gndr=&rcv_s=&rcv_e=&lup_s=&lup_e=Although melanoma vaccines have a lot of potential in theory, there has been little in
the way of positive results so far. However, the following article is encouraging:
http://www.sciencedaily.com/releases/2011/06/110602091834.htmI think that it is important for patients to have definite treatment plans in mind
with options that may be possible. So, if one treatment doesn't work I think that it is
wise to have a plan B, plan C, etc.I started reading about melanoma in early 2007, and there have been a lot of
advancements since then. However, the big problem is that melanoma is much more devious
than we imagine as it seems to actively overcome nearly all attempts to stop metastasis.
I feel that stopping metastasis is the key to treatment success.Thanks for your kind words.
Frank from Australia
-
- October 20, 2011 at 6:14 pm
Yes, Frank!! I agree with you on the adoptive cell transfer theories as well as the dendritic vaccines!! My husband is BRAF negative so Vemurafenib is not an option. I too have read extensively about the granulyte macrophage colony stimulating factor and its consequence to the cytotoxic t cells in melanoma. I feel this is very promising, but thus far I have not been able to locate a clinical trial for Stage 3b patients in the U.S. I know ECOG conducted an 800+ patient trial to determine the efficacy of GM-CSF as an adjuvant therapy but they are awaiting results. Do you know of any trials that are open in Australia? Or a website that I can search for trials in Australia? Interestingly enough, I know you must be so proud of your fellow Aussies as it is my opinion that your docs/researchers are leading the way in discovering viable antigen tumor specific therapies for this disease! I like you am hesitant to believe that one drug that signals only one pathway can slow down the progression of a disease that is known to link directly to the immune system and its numerous signalling pathways. Also, we are yet to see the long term autologous effects of the stimulation of the apoptotic phase of the cell division. I really appreciate your reply as you seem to be a kindred spirit as a "research junkie"!! Please share any other theories that you might have as I know you have been at this much longer than I. Thanks!!
-
- October 20, 2011 at 12:40 pm
PBJ, welcome to our forum. Testing for NY-ESO-1 is unusual, but I think that some people here have had the test. However, I don't know if any have had the test in relation to the possible efficacy of ipi.
I would just like to make some comments about treatments in general. Although ipi (now called Yervoy) is a valuable new treatment, neither it nor any current therapy is a guaranteed cure for metastatic melanoma. It is also very difficult to predict who will respond to what treatment.
Research is advancing quickly, but this cancer is usually able to outsmart the effects anything that we have. However, a small number of people have been able to achieve NED (no evidence of disease) for a very long time.
These are some treatments that show promise and are worth looking at, depending on eligibility criteria and availability: GM-CSF (Leukine) and surgery when needed, Yervoy, BRAF and similar inhibitors, IL-2, and anti PD-1 (MDX-1106). However, I feel that TIL treatment (adoptive cell therapy) is the option that may give suitable patients the best chance of achieving a durable remission.
Hope this helps.
Frank from Australia
-
- October 20, 2011 at 12:40 pm
PBJ, welcome to our forum. Testing for NY-ESO-1 is unusual, but I think that some people here have had the test. However, I don't know if any have had the test in relation to the possible efficacy of ipi.
I would just like to make some comments about treatments in general. Although ipi (now called Yervoy) is a valuable new treatment, neither it nor any current therapy is a guaranteed cure for metastatic melanoma. It is also very difficult to predict who will respond to what treatment.
Research is advancing quickly, but this cancer is usually able to outsmart the effects anything that we have. However, a small number of people have been able to achieve NED (no evidence of disease) for a very long time.
These are some treatments that show promise and are worth looking at, depending on eligibility criteria and availability: GM-CSF (Leukine) and surgery when needed, Yervoy, BRAF and similar inhibitors, IL-2, and anti PD-1 (MDX-1106). However, I feel that TIL treatment (adoptive cell therapy) is the option that may give suitable patients the best chance of achieving a durable remission.
Hope this helps.
Frank from Australia
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- October 22, 2011 at 2:03 pm
Hi,I was tested for NY-ESO-1 following my resection for stage IIIB in 2001. I was NY-ESO-1 positive so had a vaccine trial that was an immune stimulant + the NY-ESO protein. I have been out of the Mel loop for the last 18 months so it was actually a learning curve for me reading your post about it’s interaction with more recent treatments. Just wanted to let you know I had the NY testing but it was as part of a clinical trial not for prognosis….and it was quite a while ago so I don’t think it helps you much. I hope you find more helpful info from others….sorry I can’t offer more.
AlisonC
NED since 2001 -
- October 22, 2011 at 2:03 pm
Hi,I was tested for NY-ESO-1 following my resection for stage IIIB in 2001. I was NY-ESO-1 positive so had a vaccine trial that was an immune stimulant + the NY-ESO protein. I have been out of the Mel loop for the last 18 months so it was actually a learning curve for me reading your post about it’s interaction with more recent treatments. Just wanted to let you know I had the NY testing but it was as part of a clinical trial not for prognosis….and it was quite a while ago so I don’t think it helps you much. I hope you find more helpful info from others….sorry I can’t offer more.
AlisonC
NED since 2001 -
- October 22, 2011 at 2:03 pm
Hi,I was tested for NY-ESO-1 following my resection for stage IIIB in 2001. I was NY-ESO-1 positive so had a vaccine trial that was an immune stimulant + the NY-ESO protein. I have been out of the Mel loop for the last 18 months so it was actually a learning curve for me reading your post about it’s interaction with more recent treatments. Just wanted to let you know I had the NY testing but it was as part of a clinical trial not for prognosis….and it was quite a while ago so I don’t think it helps you much. I hope you find more helpful info from others….sorry I can’t offer more.
AlisonC
NED since 2001
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Tagged: cutaneous melanoma
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