How long for anti-pd1 to work?

I'm so sorry for your recent challenges.  I hate to say this but I just haven't heard of people having a delayed response to PD-1 like you hear with people on Ipi.  I hope I'm wrong on that.  Have you all considered TIL?  What about IL-2?  I know it's extremely tough and I'm not sure your husband would be up for it now but I have heard that NRAS patients may be more likely to respond to it.  Is the stomach tumor resectable?  Where are you located?  Sorry more questions than answers.  Really hope you doc has some good options for you on Wednesday.

I'm so sorry for your recent challenges.  I hate to say this but I just haven't heard of people having a delayed response to PD-1 like you hear with people on Ipi.  I hope I'm wrong on that.  Have you all considered TIL?  What about IL-2?  I know it's extremely tough and I'm not sure your husband would be up for it now but I have heard that NRAS patients may be more likely to respond to it.  Is the stomach tumor resectable?  Where are you located?  Sorry more questions than answers.  Really hope you doc has some good options for you on Wednesday.

I'm so sorry for your recent challenges.  I hate to say this but I just haven't heard of people having a delayed response to PD-1 like you hear with people on Ipi.  I hope I'm wrong on that.  Have you all considered TIL?  What about IL-2?  I know it's extremely tough and I'm not sure your husband would be up for it now but I have heard that NRAS patients may be more likely to respond to it.  Is the stomach tumor resectable?  Where are you located?  Sorry more questions than answers.  Really hope you doc has some good options for you on Wednesday.

Like Brian, I am sorry for all that you and your husband are going through.  However, I have heard of many patients having a delayed response to anti-PD1.  I my trial of Nivo, that began in 2010, one of the earliest participants was removed from the trial because he had progressed (he and I were both in the first arm) at the first (3 month scans).  However, as the docs monitored him to try to determine what treatment to offer next….his tumors began to shrink…WITH NO OTHER TREATMENT!!!  The tumors continued to diminish for many months that I am personally aware of. I did lose track eventually….but that is just because I no longer had access….not that things necessarily changed….though I cannot give you a certain answer either way.  Numerous articles and discussions between researchers have talked about the need to give patients on anti-PD1 TIME (just as has been discussed with ipi) to see what the response will really be.  Here is the latest one that I could lay my hands on just now.

Evaluation of immune-related response criteria in patients with advanced melanoma treated with the anti-PD1 monoclonal antibody MK-3475
Abstract 3006, J Clin Oncol
Hodi, Ribas, Hamid, Robert, Weber, Wolchok, et al

3 melanoma cohorts treated with MK-3475 2mg/kg every 3 weeks, 10mg/kg every 3 OR 2 weeks in a phase 1 trial.  Tumor imaging was performed every 12 weeks.  411 patients enrolled.  192 were on MK-3475 for 28 weeks or more as of 10/18/2013.  Tumor flare was seen in 7 patients. In these patients, best overall response was:  complete response = 1, partial response = 4, stable disease = 2.  Atypical delayed response was seen in 6 patients.  The 51 patients with progressive disease, but also WITH evidence of response using immune criteria had favorable overall survival compared with 145 patients who had progressive disease and NO evidence of response via immune criteria.  Conclusion: Conventional criteria such as RECIST may underestimate the benefit of MK-3475 in approximately 10% of treated patients.

I don't know what will be decided in regard to your husband.  But, I am keep my fingers crossed for you both. Brain's alternatives seem like good ones if needed.  Additionally, there was this by Weber in his talk with Ribas about the latest ASCO reports regarding NRAS patients:

Weber:  I was very impressed with Sosman's presentation of the CDK-4 inhibitor combined with the MEK inhibitor 162…a 33% response rate, …phase 1 study with only 22 patients….Nonetheless, the NRAS-mutated population – which are BRAF wild-type because the 2 mutations are mutually exclusive – was a relatively hopeless cohort in terms of targeted therapy, and now it looks like there will be a useful and efficacious targeted therapy for at least 15% of melanoma patients who are NRAS-mutated BRAF wild-type. 

Sosman is in Nashville at Vanderbilt.  Not sure if that helps. Hang in there, Celeste

Like Brian, I am sorry for all that you and your husband are going through.  However, I have heard of many patients having a delayed response to anti-PD1.  I my trial of Nivo, that began in 2010, one of the earliest participants was removed from the trial because he had progressed (he and I were both in the first arm) at the first (3 month scans).  However, as the docs monitored him to try to determine what treatment to offer next….his tumors began to shrink…WITH NO OTHER TREATMENT!!!  The tumors continued to diminish for many months that I am personally aware of. I did lose track eventually….but that is just because I no longer had access….not that things necessarily changed….though I cannot give you a certain answer either way.  Numerous articles and discussions between researchers have talked about the need to give patients on anti-PD1 TIME (just as has been discussed with ipi) to see what the response will really be.  Here is the latest one that I could lay my hands on just now.

Evaluation of immune-related response criteria in patients with advanced melanoma treated with the anti-PD1 monoclonal antibody MK-3475
Abstract 3006, J Clin Oncol
Hodi, Ribas, Hamid, Robert, Weber, Wolchok, et al

3 melanoma cohorts treated with MK-3475 2mg/kg every 3 weeks, 10mg/kg every 3 OR 2 weeks in a phase 1 trial.  Tumor imaging was performed every 12 weeks.  411 patients enrolled.  192 were on MK-3475 for 28 weeks or more as of 10/18/2013.  Tumor flare was seen in 7 patients. In these patients, best overall response was:  complete response = 1, partial response = 4, stable disease = 2.  Atypical delayed response was seen in 6 patients.  The 51 patients with progressive disease, but also WITH evidence of response using immune criteria had favorable overall survival compared with 145 patients who had progressive disease and NO evidence of response via immune criteria.  Conclusion: Conventional criteria such as RECIST may underestimate the benefit of MK-3475 in approximately 10% of treated patients.

I don't know what will be decided in regard to your husband.  But, I am keep my fingers crossed for you both. Brain's alternatives seem like good ones if needed.  Additionally, there was this by Weber in his talk with Ribas about the latest ASCO reports regarding NRAS patients:

Weber:  I was very impressed with Sosman's presentation of the CDK-4 inhibitor combined with the MEK inhibitor 162…a 33% response rate, …phase 1 study with only 22 patients….Nonetheless, the NRAS-mutated population – which are BRAF wild-type because the 2 mutations are mutually exclusive – was a relatively hopeless cohort in terms of targeted therapy, and now it looks like there will be a useful and efficacious targeted therapy for at least 15% of melanoma patients who are NRAS-mutated BRAF wild-type. 

Sosman is in Nashville at Vanderbilt.  Not sure if that helps. Hang in there, Celeste

Like Brian, I am sorry for all that you and your husband are going through.  However, I have heard of many patients having a delayed response to anti-PD1.  I my trial of Nivo, that began in 2010, one of the earliest participants was removed from the trial because he had progressed (he and I were both in the first arm) at the first (3 month scans).  However, as the docs monitored him to try to determine what treatment to offer next….his tumors began to shrink…WITH NO OTHER TREATMENT!!!  The tumors continued to diminish for many months that I am personally aware of. I did lose track eventually….but that is just because I no longer had access….not that things necessarily changed….though I cannot give you a certain answer either way.  Numerous articles and discussions between researchers have talked about the need to give patients on anti-PD1 TIME (just as has been discussed with ipi) to see what the response will really be.  Here is the latest one that I could lay my hands on just now.

Evaluation of immune-related response criteria in patients with advanced melanoma treated with the anti-PD1 monoclonal antibody MK-3475
Abstract 3006, J Clin Oncol
Hodi, Ribas, Hamid, Robert, Weber, Wolchok, et al

3 melanoma cohorts treated with MK-3475 2mg/kg every 3 weeks, 10mg/kg every 3 OR 2 weeks in a phase 1 trial.  Tumor imaging was performed every 12 weeks.  411 patients enrolled.  192 were on MK-3475 for 28 weeks or more as of 10/18/2013.  Tumor flare was seen in 7 patients. In these patients, best overall response was:  complete response = 1, partial response = 4, stable disease = 2.  Atypical delayed response was seen in 6 patients.  The 51 patients with progressive disease, but also WITH evidence of response using immune criteria had favorable overall survival compared with 145 patients who had progressive disease and NO evidence of response via immune criteria.  Conclusion: Conventional criteria such as RECIST may underestimate the benefit of MK-3475 in approximately 10% of treated patients.

I don't know what will be decided in regard to your husband.  But, I am keep my fingers crossed for you both. Brain's alternatives seem like good ones if needed.  Additionally, there was this by Weber in his talk with Ribas about the latest ASCO reports regarding NRAS patients:

Weber:  I was very impressed with Sosman's presentation of the CDK-4 inhibitor combined with the MEK inhibitor 162…a 33% response rate, …phase 1 study with only 22 patients….Nonetheless, the NRAS-mutated population – which are BRAF wild-type because the 2 mutations are mutually exclusive – was a relatively hopeless cohort in terms of targeted therapy, and now it looks like there will be a useful and efficacious targeted therapy for at least 15% of melanoma patients who are NRAS-mutated BRAF wild-type. 

Sosman is in Nashville at Vanderbilt.  Not sure if that helps. Hang in there, Celeste

I had a later response to pd1's MK-3475.  And I am doing great now.

When I started pd1 I had metastisis in both arm pits, behind my chestwall, wrapped around my heart, and a mass on my liver.  The biopsied node in my right arm pit that got me into the trial was a little bigger than a grape in size.

I scanned again 3 months later and all the disease disappeared everywhere (and has not returned,) except that one bad node in my right arm pit had doubled in size and now was the size of a ping-pong ball.  Then again 3 months after that (so 6 months into the pd1 trial) the bad node had now doubled in size again and was more like a peach.  So the doctors started to really think that the pd1 wasn't working and the they almost took me off of treatment. 

I was one week from meeting with the surgeon to talk about surgery when I started experiencing stabbing pains to my bad node.  Those pains continued for 24 hours every 5-8 seconds.  It was scary and I didn't understand, but my doctors said that it sounded like it was finally responding to treatment.  I woke up the next day and that node was the size of a baseball and hanging out of my arm pit.  But two days after that, it was back to a smaller size and it was no longer hanging out of me.  I scanned and it showed that the node had liquified and the doctors said that meant it was dying.  That the treatment had worked.  And it has been going back down in size, about 15% smaller every 5 weeks, ever since. 

I am now doing great.  Still no reoccurances anywhere else and that node is back down to the size of a thumb nail. 

Pd1 was also not so rough on my immue system.  I've been pretty healthy the whole time and able to work full time, no problem.  So hang in there!  You too could just need a little more time.  🙂

Laurie

I had a later response to pd1's MK-3475.  And I am doing great now.

When I started pd1 I had metastisis in both arm pits, behind my chestwall, wrapped around my heart, and a mass on my liver.  The biopsied node in my right arm pit that got me into the trial was a little bigger than a grape in size.

I scanned again 3 months later and all the disease disappeared everywhere (and has not returned,) except that one bad node in my right arm pit had doubled in size and now was the size of a ping-pong ball.  Then again 3 months after that (so 6 months into the pd1 trial) the bad node had now doubled in size again and was more like a peach.  So the doctors started to really think that the pd1 wasn't working and the they almost took me off of treatment. 

I was one week from meeting with the surgeon to talk about surgery when I started experiencing stabbing pains to my bad node.  Those pains continued for 24 hours every 5-8 seconds.  It was scary and I didn't understand, but my doctors said that it sounded like it was finally responding to treatment.  I woke up the next day and that node was the size of a baseball and hanging out of my arm pit.  But two days after that, it was back to a smaller size and it was no longer hanging out of me.  I scanned and it showed that the node had liquified and the doctors said that meant it was dying.  That the treatment had worked.  And it has been going back down in size, about 15% smaller every 5 weeks, ever since. 

I am now doing great.  Still no reoccurances anywhere else and that node is back down to the size of a thumb nail. 

Pd1 was also not so rough on my immue system.  I've been pretty healthy the whole time and able to work full time, no problem.  So hang in there!  You too could just need a little more time.  🙂

Laurie

I had a later response to pd1's MK-3475.  And I am doing great now.

When I started pd1 I had metastisis in both arm pits, behind my chestwall, wrapped around my heart, and a mass on my liver.  The biopsied node in my right arm pit that got me into the trial was a little bigger than a grape in size.

I scanned again 3 months later and all the disease disappeared everywhere (and has not returned,) except that one bad node in my right arm pit had doubled in size and now was the size of a ping-pong ball.  Then again 3 months after that (so 6 months into the pd1 trial) the bad node had now doubled in size again and was more like a peach.  So the doctors started to really think that the pd1 wasn't working and the they almost took me off of treatment. 

I was one week from meeting with the surgeon to talk about surgery when I started experiencing stabbing pains to my bad node.  Those pains continued for 24 hours every 5-8 seconds.  It was scary and I didn't understand, but my doctors said that it sounded like it was finally responding to treatment.  I woke up the next day and that node was the size of a baseball and hanging out of my arm pit.  But two days after that, it was back to a smaller size and it was no longer hanging out of me.  I scanned and it showed that the node had liquified and the doctors said that meant it was dying.  That the treatment had worked.  And it has been going back down in size, about 15% smaller every 5 weeks, ever since. 

I am now doing great.  Still no reoccurances anywhere else and that node is back down to the size of a thumb nail. 

Pd1 was also not so rough on my immue system.  I've been pretty healthy the whole time and able to work full time, no problem.  So hang in there!  You too could just need a little more time.  🙂

Laurie

Interesting thread, with lots of good information from folks here. I'll add my more anecdotal reply. I had a pretty quick response to TIL (and/or IL-2) and the subsequent additional response — that could possibly all better be described as a sustained response, but…  along the way, I've had several mets that have occurred one or two at a time and haven't been terribly agressive that we've tactically addressed with radiation or surgery. There's no one to know for sure, that could simply be the nature of my particular disease or could be that these immunotherapies with sustained responses have not necessarily allowed me to reach NED but have played a role in slowing progression.

After finishing my course of ipi, I was talking with my medical oncologist about ipi and the anti-PD-1's and the conundrum of delayed responses. He mentioned several patients that have come in during treatment for regular scans that show disease progression:  increased size of tumors on CT, increased uptake on PET, etc. But he then hears from some statements akin to, "Doctor, I know things look bad, but I have to tell you, I feel great, better than I have in a long time." That's very subjective, but also telling that perhaps there is something at work. There are two aspects to a delayed response: first, that it just can sometimes take time for the immune system to mount a response (hence the term "delayed response"). Second, when a response does occur, it can often manifest itself physically on a scan as disease progression, sometime significant. As the T-cells rush to the tumors, size increases, and as those T-cells start attacking melanoma cells, metabolic activity also increases — the same two indicators of disease activity and growth.

This all will be an important part of advancing immunotherapies. Obviously trying to identify patients ahead of time that will respond to immunotherapies, and which ones. But also trying to find markers and other indicators to differentiate disease progression from immunotherapy response. Hearing, "I feel great," is a good thing, but not enough to just assume that all is going well. Yervoy is a great example. Without getting into detailed response rates, using roughly 20%, if a patient shows increased tumor size or activity on a scan, statistically, that roughly equates to an 80% chance of disease progression vs. 20% chance of early response indication. Most patients, rightfully so and without additional markers to say it's an early response, are going to say, "O.K. doc, what's next?" and move on to the next treatment if one is available. The same has been seen with TIL and will be seen with anti-PD-1.

Joe

Interesting thread, with lots of good information from folks here. I'll add my more anecdotal reply. I had a pretty quick response to TIL (and/or IL-2) and the subsequent additional response — that could possibly all better be described as a sustained response, but…  along the way, I've had several mets that have occurred one or two at a time and haven't been terribly agressive that we've tactically addressed with radiation or surgery. There's no one to know for sure, that could simply be the nature of my particular disease or could be that these immunotherapies with sustained responses have not necessarily allowed me to reach NED but have played a role in slowing progression.

After finishing my course of ipi, I was talking with my medical oncologist about ipi and the anti-PD-1's and the conundrum of delayed responses. He mentioned several patients that have come in during treatment for regular scans that show disease progression:  increased size of tumors on CT, increased uptake on PET, etc. But he then hears from some statements akin to, "Doctor, I know things look bad, but I have to tell you, I feel great, better than I have in a long time." That's very subjective, but also telling that perhaps there is something at work. There are two aspects to a delayed response: first, that it just can sometimes take time for the immune system to mount a response (hence the term "delayed response"). Second, when a response does occur, it can often manifest itself physically on a scan as disease progression, sometime significant. As the T-cells rush to the tumors, size increases, and as those T-cells start attacking melanoma cells, metabolic activity also increases — the same two indicators of disease activity and growth.

This all will be an important part of advancing immunotherapies. Obviously trying to identify patients ahead of time that will respond to immunotherapies, and which ones. But also trying to find markers and other indicators to differentiate disease progression from immunotherapy response. Hearing, "I feel great," is a good thing, but not enough to just assume that all is going well. Yervoy is a great example. Without getting into detailed response rates, using roughly 20%, if a patient shows increased tumor size or activity on a scan, statistically, that roughly equates to an 80% chance of disease progression vs. 20% chance of early response indication. Most patients, rightfully so and without additional markers to say it's an early response, are going to say, "O.K. doc, what's next?" and move on to the next treatment if one is available. The same has been seen with TIL and will be seen with anti-PD-1.

Joe

Interesting thread, with lots of good information from folks here. I'll add my more anecdotal reply. I had a pretty quick response to TIL (and/or IL-2) and the subsequent additional response — that could possibly all better be described as a sustained response, but…  along the way, I've had several mets that have occurred one or two at a time and haven't been terribly agressive that we've tactically addressed with radiation or surgery. There's no one to know for sure, that could simply be the nature of my particular disease or could be that these immunotherapies with sustained responses have not necessarily allowed me to reach NED but have played a role in slowing progression.

After finishing my course of ipi, I was talking with my medical oncologist about ipi and the anti-PD-1's and the conundrum of delayed responses. He mentioned several patients that have come in during treatment for regular scans that show disease progression:  increased size of tumors on CT, increased uptake on PET, etc. But he then hears from some statements akin to, "Doctor, I know things look bad, but I have to tell you, I feel great, better than I have in a long time." That's very subjective, but also telling that perhaps there is something at work. There are two aspects to a delayed response: first, that it just can sometimes take time for the immune system to mount a response (hence the term "delayed response"). Second, when a response does occur, it can often manifest itself physically on a scan as disease progression, sometime significant. As the T-cells rush to the tumors, size increases, and as those T-cells start attacking melanoma cells, metabolic activity also increases — the same two indicators of disease activity and growth.

This all will be an important part of advancing immunotherapies. Obviously trying to identify patients ahead of time that will respond to immunotherapies, and which ones. But also trying to find markers and other indicators to differentiate disease progression from immunotherapy response. Hearing, "I feel great," is a good thing, but not enough to just assume that all is going well. Yervoy is a great example. Without getting into detailed response rates, using roughly 20%, if a patient shows increased tumor size or activity on a scan, statistically, that roughly equates to an 80% chance of disease progression vs. 20% chance of early response indication. Most patients, rightfully so and without additional markers to say it's an early response, are going to say, "O.K. doc, what's next?" and move on to the next treatment if one is available. The same has been seen with TIL and will be seen with anti-PD-1.

Joe