Great Info on melanoma blood markers and progression

You might want to change the title of your post to " Dr. Answers questions about how we don't have blood makers that help at this time".

You might want to change the title of your post to " Dr. Answers questions about how we don't have blood makers that help at this time".

You might want to change the title of your post to " Dr. Answers questions about how we don't have blood makers that help at this time".

I don't know what blood markers are referenced in the original post, as I can't access the article.  However, there are blood markers, and they've been used to measure disease progress and drug response.  For instance, see…

Reynolds et al. (2006) Cytoplasmic melanoma-associated antigen (CYT-MAA) serum level in patients with melanoma: a potential marker of response to immunotherapy?  Int. J. Cancer: 119:157-161.

Reynolds et al. (2003) Changes in the presence of multiple markers of circulating melanoma cells correlate with clinical outcome in patients with melanoma.  Clin. Cancer Res. 9:1497-1502.

These papers cite other studies discussing blood markers.

If you look at the second reply by anon, he or she put up a link that now works. Ed

Ah, there it is!  Thanks!

The following was asked/answered:

» STAGE II CIRCULATING TUMORS CELLS
Is there a way to measure circulating tumor cells ? I’ve heard that there is melanoma in the blood for all patients at all stages, but they use a different measuring methodology? Can you please clarify this?

Dr. Joseph: “Circulating tumor cells is another area of great interest for many researchers. Circulating melanoma cells can be detected in the blood through various techniques. At present, detecting circulating melanoma cells in the blood would be considered experimental. Some of the potential uses of detecting circulating melanoma cells include the following: 1) quantifying the number of cells as a means to detect early recurrence 2) determining if the number of cells associate with the efficacy of therapy 3) ability to analyze the “tumor” without performing a biopsy.”

So it would appear that the physician draws a distinction between testing widely sanctioned by the medical community (e.g. FDA approved?) and testing that is done in academic settings.  This might translate to what is available to you and me in ordinarily accessible medical settings vs. what is available to the participant in some clinical trial. 

One of the links I posted does examine markers on circulating cells as a measure of clinical outcome.  These markers are antigens expressed on the circulating melanoma cells.  Absence of these markers was taken to be evidence of absence of circulating melanoma cells. 

The authors found that…

Irregardless, it appears that when the doctor says there are no tests, he means that these tests are not commonly available outside of academic settings. 

Thanks for the articles ET!  They are interesting but a little out of date to what is happening in the Melanoma field. One of the leading names in Melanoma is Dr. Antoni Ribas of UCLA, and I would recommend you take a look at his webinar on Cancer Research Institute, titled "Break thoughs in Cancer Immunotherapy, What's next for patients."Date of webinar is May 12, 2015. Around the 21 min mark he gets into predicting responses in Immunotherapy. Most  Melanoma patients that are at advanced stages are having break throughs with Immunotherapy. Now that we know that these drug work for many patients but not all, the question that has been asked is can we predict who will respond and to which drug. Dr. Antoni Ribas talks about some of his research with Cd8 infiltrating cells and pd-l and pd-L1 expression. It seems that the best way to predict Melanoma responses at present lies with what is happening in the tumor and not with blood tests. I know that the big pharmaceutical companies are looking for blood tests to be able to predict which Melanoma drug will work, but to my knowledge they haven't developed one for Immunotherapy drugs yet.Wishing you the best!!! Ed

Hi Ed,

Yes, they're old, but vaccine therapy research has crawled along since its boom in the 80's, only to see a resurgence lately.  I think vaccines may eventually be used in combination with checkpoint blockades — seems a reasonable combination.  The only reason I'm reading these studies is that they are part of the background behind the seviprotimut-L vaccine in phase III trials (for which ET may be a participant).  The vaccine was actually developed in the mid 80's before all of immunological approahces were deemed irrelevant to cancer treatment in the 90's.  Funny how science works sometimes.

Part of the reason these tests might not be widely available is that they are very labor intensive and can't be stocked on a shelf.  The study on markers from circulating melanoma cells used an assay involving reverse transcription PCA (polymerase chain reaction).  This is an amplification technique very similar to that used for DNA testing in crime investigations.

I've watched Dr. Ribas' webinar and several others.  They're all quite interesting, and they've done much especially to further ET's understanding of the subject matter (and certainly mine too).  Research papers are very dry reading, and ET has had to learn not only immunology, but something of the scientific method and the conventions of statistical analysis and dissemination of findings in the literature.  Fortunately I'm able to tutor her a bit on all of this.  It's still a very steep learning curve.

Anyway, the best way currently to assess progress may be tumor size and progression-free survival periods.  However, I believe testing for blood markers may eventually be the fastest way to determine if the patient is on a productive treatment path or whether a different path should be considered.  "Fast" is important, because wasted time and wrong turns both kill.  The more gadgets in the physician's toolbox, the better.  😉

Hi Ed,

Yes, they're old, but vaccine therapy research has crawled along since its boom in the 80's, only to see a resurgence lately.  I think vaccines may eventually be used in combination with checkpoint blockades — seems a reasonable combination.  The only reason I'm reading these studies is that they are part of the background behind the seviprotimut-L vaccine in phase III trials (for which ET may be a participant).  The vaccine was actually developed in the mid 80's before all of immunological approahces were deemed irrelevant to cancer treatment in the 90's.  Funny how science works sometimes.

Part of the reason these tests might not be widely available is that they are very labor intensive and can't be stocked on a shelf.  The study on markers from circulating melanoma cells used an assay involving reverse transcription PCA (polymerase chain reaction).  This is an amplification technique very similar to that used for DNA testing in crime investigations.

I've watched Dr. Ribas' webinar and several others.  They're all quite interesting, and they've done much especially to further ET's understanding of the subject matter (and certainly mine too).  Research papers are very dry reading, and ET has had to learn not only immunology, but something of the scientific method and the conventions of statistical analysis and dissemination of findings in the literature.  Fortunately I'm able to tutor her a bit on all of this.  It's still a very steep learning curve.

Anyway, the best way currently to assess progress may be tumor size and progression-free survival periods.  However, I believe testing for blood markers may eventually be the fastest way to determine if the patient is on a productive treatment path or whether a different path should be considered.  "Fast" is important, because wasted time and wrong turns both kill.  The more gadgets in the physician's toolbox, the better.  😉

Hi Ed,

Yes, they're old, but vaccine therapy research has crawled along since its boom in the 80's, only to see a resurgence lately.  I think vaccines may eventually be used in combination with checkpoint blockades — seems a reasonable combination.  The only reason I'm reading these studies is that they are part of the background behind the seviprotimut-L vaccine in phase III trials (for which ET may be a participant).  The vaccine was actually developed in the mid 80's before all of immunological approahces were deemed irrelevant to cancer treatment in the 90's.  Funny how science works sometimes.

Part of the reason these tests might not be widely available is that they are very labor intensive and can't be stocked on a shelf.  The study on markers from circulating melanoma cells used an assay involving reverse transcription PCA (polymerase chain reaction).  This is an amplification technique very similar to that used for DNA testing in crime investigations.

I've watched Dr. Ribas' webinar and several others.  They're all quite interesting, and they've done much especially to further ET's understanding of the subject matter (and certainly mine too).  Research papers are very dry reading, and ET has had to learn not only immunology, but something of the scientific method and the conventions of statistical analysis and dissemination of findings in the literature.  Fortunately I'm able to tutor her a bit on all of this.  It's still a very steep learning curve.

Anyway, the best way currently to assess progress may be tumor size and progression-free survival periods.  However, I believe testing for blood markers may eventually be the fastest way to determine if the patient is on a productive treatment path or whether a different path should be considered.  "Fast" is important, because wasted time and wrong turns both kill.  The more gadgets in the physician's toolbox, the better.  😉

Thanks for the articles ET!  They are interesting but a little out of date to what is happening in the Melanoma field. One of the leading names in Melanoma is Dr. Antoni Ribas of UCLA, and I would recommend you take a look at his webinar on Cancer Research Institute, titled "Break thoughs in Cancer Immunotherapy, What's next for patients."Date of webinar is May 12, 2015. Around the 21 min mark he gets into predicting responses in Immunotherapy. Most  Melanoma patients that are at advanced stages are having break throughs with Immunotherapy. Now that we know that these drug work for many patients but not all, the question that has been asked is can we predict who will respond and to which drug. Dr. Antoni Ribas talks about some of his research with Cd8 infiltrating cells and pd-l and pd-L1 expression. It seems that the best way to predict Melanoma responses at present lies with what is happening in the tumor and not with blood tests. I know that the big pharmaceutical companies are looking for blood tests to be able to predict which Melanoma drug will work, but to my knowledge they haven't developed one for Immunotherapy drugs yet.Wishing you the best!!! Ed

Thanks for the articles ET!  They are interesting but a little out of date to what is happening in the Melanoma field. One of the leading names in Melanoma is Dr. Antoni Ribas of UCLA, and I would recommend you take a look at his webinar on Cancer Research Institute, titled "Break thoughs in Cancer Immunotherapy, What's next for patients."Date of webinar is May 12, 2015. Around the 21 min mark he gets into predicting responses in Immunotherapy. Most  Melanoma patients that are at advanced stages are having break throughs with Immunotherapy. Now that we know that these drug work for many patients but not all, the question that has been asked is can we predict who will respond and to which drug. Dr. Antoni Ribas talks about some of his research with Cd8 infiltrating cells and pd-l and pd-L1 expression. It seems that the best way to predict Melanoma responses at present lies with what is happening in the tumor and not with blood tests. I know that the big pharmaceutical companies are looking for blood tests to be able to predict which Melanoma drug will work, but to my knowledge they haven't developed one for Immunotherapy drugs yet.Wishing you the best!!! Ed

Ah, there it is!  Thanks!

The following was asked/answered:

» STAGE II CIRCULATING TUMORS CELLS
Is there a way to measure circulating tumor cells ? I’ve heard that there is melanoma in the blood for all patients at all stages, but they use a different measuring methodology? Can you please clarify this?

Dr. Joseph: “Circulating tumor cells is another area of great interest for many researchers. Circulating melanoma cells can be detected in the blood through various techniques. At present, detecting circulating melanoma cells in the blood would be considered experimental. Some of the potential uses of detecting circulating melanoma cells include the following: 1) quantifying the number of cells as a means to detect early recurrence 2) determining if the number of cells associate with the efficacy of therapy 3) ability to analyze the “tumor” without performing a biopsy.”

So it would appear that the physician draws a distinction between testing widely sanctioned by the medical community (e.g. FDA approved?) and testing that is done in academic settings.  This might translate to what is available to you and me in ordinarily accessible medical settings vs. what is available to the participant in some clinical trial. 

One of the links I posted does examine markers on circulating cells as a measure of clinical outcome.  These markers are antigens expressed on the circulating melanoma cells.  Absence of these markers was taken to be evidence of absence of circulating melanoma cells. 

The authors found that…

Irregardless, it appears that when the doctor says there are no tests, he means that these tests are not commonly available outside of academic settings. 

Ah, there it is!  Thanks!

The following was asked/answered:

» STAGE II CIRCULATING TUMORS CELLS
Is there a way to measure circulating tumor cells ? I’ve heard that there is melanoma in the blood for all patients at all stages, but they use a different measuring methodology? Can you please clarify this?

Dr. Joseph: “Circulating tumor cells is another area of great interest for many researchers. Circulating melanoma cells can be detected in the blood through various techniques. At present, detecting circulating melanoma cells in the blood would be considered experimental. Some of the potential uses of detecting circulating melanoma cells include the following: 1) quantifying the number of cells as a means to detect early recurrence 2) determining if the number of cells associate with the efficacy of therapy 3) ability to analyze the “tumor” without performing a biopsy.”

So it would appear that the physician draws a distinction between testing widely sanctioned by the medical community (e.g. FDA approved?) and testing that is done in academic settings.  This might translate to what is available to you and me in ordinarily accessible medical settings vs. what is available to the participant in some clinical trial. 

One of the links I posted does examine markers on circulating cells as a measure of clinical outcome.  These markers are antigens expressed on the circulating melanoma cells.  Absence of these markers was taken to be evidence of absence of circulating melanoma cells. 

The authors found that…

Irregardless, it appears that when the doctor says there are no tests, he means that these tests are not commonly available outside of academic settings. 

If you look at the second reply by anon, he or she put up a link that now works. Ed

If you look at the second reply by anon, he or she put up a link that now works. Ed

I don't know what blood markers are referenced in the original post, as I can't access the article.  However, there are blood markers, and they've been used to measure disease progress and drug response.  For instance, see…

Reynolds et al. (2006) Cytoplasmic melanoma-associated antigen (CYT-MAA) serum level in patients with melanoma: a potential marker of response to immunotherapy?  Int. J. Cancer: 119:157-161.

Reynolds et al. (2003) Changes in the presence of multiple markers of circulating melanoma cells correlate with clinical outcome in patients with melanoma.  Clin. Cancer Res. 9:1497-1502.

These papers cite other studies discussing blood markers.

I don't know what blood markers are referenced in the original post, as I can't access the article.  However, there are blood markers, and they've been used to measure disease progress and drug response.  For instance, see…

Reynolds et al. (2006) Cytoplasmic melanoma-associated antigen (CYT-MAA) serum level in patients with melanoma: a potential marker of response to immunotherapy?  Int. J. Cancer: 119:157-161.

Reynolds et al. (2003) Changes in the presence of multiple markers of circulating melanoma cells correlate with clinical outcome in patients with melanoma.  Clin. Cancer Res. 9:1497-1502.

These papers cite other studies discussing blood markers.

Celeste, I suspect the doctor in the article at MIF is providing is the best evidence-based information available today. The small studies you cite (n=59 for IPI, n=69 for IPI, n=29 for PD1) I doubt make the cut as evidence-based medicine or anything we can take "to the bank". Cutting edge info from small studies may or may not pan out over the long run.

Another way of saying that is exactly what Dr. Joseph says: "…at present, there are no routine blood markers that tell you how well your immune system is working. With that being said, many groups are analyzing non-routine aspects of the blood in order to determine how the immune system might be changing while on immunotherapy." So it seems to me that Dr. Joseph is really providing the information patients can bank on today as far as blood markers and immunotherapy.

I though the article provided other great insights from a practicing oncologist who sees patients every day, too. For example, I found this very interesting: "In general, when I assess melanoma patients on therapy, I pay attention to three things: how they are feeling (most important), scans (second most important), labs (least important)." Which he expands on some more.

Celeste, I suspect the doctor in the article at MIF is providing is the best evidence-based information available today. The small studies you cite (n=59 for IPI, n=69 for IPI, n=29 for PD1) I doubt make the cut as evidence-based medicine or anything we can take "to the bank". Cutting edge info from small studies may or may not pan out over the long run.

Another way of saying that is exactly what Dr. Joseph says: "…at present, there are no routine blood markers that tell you how well your immune system is working. With that being said, many groups are analyzing non-routine aspects of the blood in order to determine how the immune system might be changing while on immunotherapy." So it seems to me that Dr. Joseph is really providing the information patients can bank on today as far as blood markers and immunotherapy.

I though the article provided other great insights from a practicing oncologist who sees patients every day, too. For example, I found this very interesting: "In general, when I assess melanoma patients on therapy, I pay attention to three things: how they are feeling (most important), scans (second most important), labs (least important)." Which he expands on some more.

Kyle,

I do not disagree with anything you or the doc is saying.  IF and MAYBE are still very big words in melanoma markers and predictive blood tests.  What I AM saying is that there are simple blood tests done on ALL of us every time we have a recheck that if WE and our docs start paying attention to…albeit, not in an official trial of 30 = n….we MAY (only may…unfortunately)  discover have much greater meaning than the fancy stuff….for now.  I have plenty of scientific articles on my blog about how if your tumor tests positive for this or negative for that you SHOULD do this, or you SHOULD NOT do that….but they all still have big IF's and MAYBE's…AND….are not readily available.  So…even if they are great….in the future….right now…too many folks are lacking access. 

I evaluate patients daily at work.  And, yes….Of primary importance…what does the patient tell you they are experiencing?  Second, what does the physical exam and their scans say?  Labs…comme ci comme ca…OR….mas o menos….language choice up to you.  Just thought I'd share some very recent data that might affect more peeps since they are readily available, FDA approved lab evals, done on EVERYBODY.

c

Kyle,

I do not disagree with anything you or the doc is saying.  IF and MAYBE are still very big words in melanoma markers and predictive blood tests.  What I AM saying is that there are simple blood tests done on ALL of us every time we have a recheck that if WE and our docs start paying attention to…albeit, not in an official trial of 30 = n….we MAY (only may…unfortunately)  discover have much greater meaning than the fancy stuff….for now.  I have plenty of scientific articles on my blog about how if your tumor tests positive for this or negative for that you SHOULD do this, or you SHOULD NOT do that….but they all still have big IF's and MAYBE's…AND….are not readily available.  So…even if they are great….in the future….right now…too many folks are lacking access. 

I evaluate patients daily at work.  And, yes….Of primary importance…what does the patient tell you they are experiencing?  Second, what does the physical exam and their scans say?  Labs…comme ci comme ca…OR….mas o menos….language choice up to you.  Just thought I'd share some very recent data that might affect more peeps since they are readily available, FDA approved lab evals, done on EVERYBODY.

c

Kyle,

I do not disagree with anything you or the doc is saying.  IF and MAYBE are still very big words in melanoma markers and predictive blood tests.  What I AM saying is that there are simple blood tests done on ALL of us every time we have a recheck that if WE and our docs start paying attention to…albeit, not in an official trial of 30 = n….we MAY (only may…unfortunately)  discover have much greater meaning than the fancy stuff….for now.  I have plenty of scientific articles on my blog about how if your tumor tests positive for this or negative for that you SHOULD do this, or you SHOULD NOT do that….but they all still have big IF's and MAYBE's…AND….are not readily available.  So…even if they are great….in the future….right now…too many folks are lacking access. 

I evaluate patients daily at work.  And, yes….Of primary importance…what does the patient tell you they are experiencing?  Second, what does the physical exam and their scans say?  Labs…comme ci comme ca…OR….mas o menos….language choice up to you.  Just thought I'd share some very recent data that might affect more peeps since they are readily available, FDA approved lab evals, done on EVERYBODY.

c

Celeste, I suspect the doctor in the article at MIF is providing is the best evidence-based information available today. The small studies you cite (n=59 for IPI, n=69 for IPI, n=29 for PD1) I doubt make the cut as evidence-based medicine or anything we can take "to the bank". Cutting edge info from small studies may or may not pan out over the long run.

Another way of saying that is exactly what Dr. Joseph says: "…at present, there are no routine blood markers that tell you how well your immune system is working. With that being said, many groups are analyzing non-routine aspects of the blood in order to determine how the immune system might be changing while on immunotherapy." So it seems to me that Dr. Joseph is really providing the information patients can bank on today as far as blood markers and immunotherapy.

I though the article provided other great insights from a practicing oncologist who sees patients every day, too. For example, I found this very interesting: "In general, when I assess melanoma patients on therapy, I pay attention to three things: how they are feeling (most important), scans (second most important), labs (least important)." Which he expands on some more.