Living with Stable Disease (G-Samsa and Joe)

Brian,

   There's another category of patients too. My husband is also on the ipi/nivo trial, but one lung nodule is not responding to the PD1, while the other eight have been stable for four months.My husband has had 50 percent shrinkage. Dr. Kirkwood said that that has happened to other patients too. Patient#1in Philly has the same issue of PD1 working on most tumors while not working on others. I also believe that his adernal gland has to be removed and it was a new tumor. Immunotherapy is going to bring about many categories of patients and hopefully many that are stable or NED.

Maureen

Brian,

   There's another category of patients too. My husband is also on the ipi/nivo trial, but one lung nodule is not responding to the PD1, while the other eight have been stable for four months.My husband has had 50 percent shrinkage. Dr. Kirkwood said that that has happened to other patients too. Patient#1in Philly has the same issue of PD1 working on most tumors while not working on others. I also believe that his adernal gland has to be removed and it was a new tumor. Immunotherapy is going to bring about many categories of patients and hopefully many that are stable or NED.

Maureen

I've gone through and heard of similar experiences. Of the systemic immunotherapies I've had, IL-2, TIL, and ipi, my doctor at my home hospital, my doctors at NIH, and others we've spoken with believe the good response I've had has been because of the TIL. But stuff has crept through, notably a stretch of five different  mets in three different long bones (tibia and femur) of my legs that didn't respond while the others were literally melting away. More than once, my doctors have used the terms "safe haven" and "safe harbor" when describing what my melanoma was doing in the bones. There isn't a clear clinical reason why that would be, it's not as if there aren't blood vessels in the bones (they're actually dense with blood vessels) that would prevent TILs or other systemic treatments from reaching these mets.

My doctor also mentioned to me that he was at a recent melanoma conference and was discussing my case with Dr. O'Day (BH Cancer Center, was at Angeles, I think?) and that this indeed is something they're seeing more of — not necessarily always bone, but good responses tempered with a low burden of mets that don't seem to respond, but also aren't terribly aggressive. 

The strategy that's worked for us and O'Day said they've used has been to manage these with the traditional treatments of surgery or radiation as appropriate. We've taken to calling it "spot welding" — I've come to feel like I'm being held together by those welds and a maybe also a few rolls of duct tape, it really completes the image 😉

A good example is the lung met I had. Found on my regular PET last October and relatively small at 1.2-cm. But going back to three-month PETs to as early as the previous January, it was there, with slight growth from scan to scan. Knowing the nature of PET, I don't view it as something "they missed", if you go looking too hard at PET for every little thing, you'll find something and this clearly wasn't acting aggressive. So in October, even then it was a case of, "Yes, given your history, this is likely melanoma, but let's watch it a little first." First reaction is, "Get it out now!" but we went ahead and did a CT at six weeks and it looked relatively stable. Another six weeks and my regular PET came up again, the size was maybe 1.3-cm, not significant considering the CT part of PET-CT is lower power/resolution, but the SUV (metabolic brightness) had gone up some. Again, not terribly aggressive, but something that would need taken care if at some point.

So at that point just this past January, it seemed like wasting a bullet to try BRAF or a BRAF/MEK combo or look at a PD-1 trial. Save those for if or when I need them. We could have waited and watched more. It wasn't going to go away on its own, but it wasn't causing issues, wasn't going to be a source of more mets (which I've always found interesting), and was asymptomatic. But after talking with my radiation oncologist, all agreed that we had a good opportunity for more "spot welding". Everything else was relatively quiet, so let's just take the opportunity to knock it out now when there are no other complicating factors. 5 sessions of SBRT (radiation) over two weeks in February. In the April PET it was already smaller and dimmer and in my PET last week, it didn't even make the radiology report. I've posted elsewhere here about the effective use of radiation, but for us it's been a part of managing my disease and more and more, sounds like it is a part of the strategy for others. As scary as my brain met was, I include it in this whole thing, too. One met, sort of out of the blue, with the biggest difference being that the location requires that it be treated in much more quickly.

Long story short, though, these "rogue tumors" are becoming a common theme for some, but there are management strategies for them — an issue for us "near-NEDs", "pseudo-NEDs", or whatever you want to call us, and others who are having good responses to immunotherapies.

Joe

I've gone through and heard of similar experiences. Of the systemic immunotherapies I've had, IL-2, TIL, and ipi, my doctor at my home hospital, my doctors at NIH, and others we've spoken with believe the good response I've had has been because of the TIL. But stuff has crept through, notably a stretch of five different  mets in three different long bones (tibia and femur) of my legs that didn't respond while the others were literally melting away. More than once, my doctors have used the terms "safe haven" and "safe harbor" when describing what my melanoma was doing in the bones. There isn't a clear clinical reason why that would be, it's not as if there aren't blood vessels in the bones (they're actually dense with blood vessels) that would prevent TILs or other systemic treatments from reaching these mets.

My doctor also mentioned to me that he was at a recent melanoma conference and was discussing my case with Dr. O'Day (BH Cancer Center, was at Angeles, I think?) and that this indeed is something they're seeing more of — not necessarily always bone, but good responses tempered with a low burden of mets that don't seem to respond, but also aren't terribly aggressive. 

The strategy that's worked for us and O'Day said they've used has been to manage these with the traditional treatments of surgery or radiation as appropriate. We've taken to calling it "spot welding" — I've come to feel like I'm being held together by those welds and a maybe also a few rolls of duct tape, it really completes the image 😉

A good example is the lung met I had. Found on my regular PET last October and relatively small at 1.2-cm. But going back to three-month PETs to as early as the previous January, it was there, with slight growth from scan to scan. Knowing the nature of PET, I don't view it as something "they missed", if you go looking too hard at PET for every little thing, you'll find something and this clearly wasn't acting aggressive. So in October, even then it was a case of, "Yes, given your history, this is likely melanoma, but let's watch it a little first." First reaction is, "Get it out now!" but we went ahead and did a CT at six weeks and it looked relatively stable. Another six weeks and my regular PET came up again, the size was maybe 1.3-cm, not significant considering the CT part of PET-CT is lower power/resolution, but the SUV (metabolic brightness) had gone up some. Again, not terribly aggressive, but something that would need taken care if at some point.

So at that point just this past January, it seemed like wasting a bullet to try BRAF or a BRAF/MEK combo or look at a PD-1 trial. Save those for if or when I need them. We could have waited and watched more. It wasn't going to go away on its own, but it wasn't causing issues, wasn't going to be a source of more mets (which I've always found interesting), and was asymptomatic. But after talking with my radiation oncologist, all agreed that we had a good opportunity for more "spot welding". Everything else was relatively quiet, so let's just take the opportunity to knock it out now when there are no other complicating factors. 5 sessions of SBRT (radiation) over two weeks in February. In the April PET it was already smaller and dimmer and in my PET last week, it didn't even make the radiology report. I've posted elsewhere here about the effective use of radiation, but for us it's been a part of managing my disease and more and more, sounds like it is a part of the strategy for others. As scary as my brain met was, I include it in this whole thing, too. One met, sort of out of the blue, with the biggest difference being that the location requires that it be treated in much more quickly.

Long story short, though, these "rogue tumors" are becoming a common theme for some, but there are management strategies for them — an issue for us "near-NEDs", "pseudo-NEDs", or whatever you want to call us, and others who are having good responses to immunotherapies.

Joe

I've gone through and heard of similar experiences. Of the systemic immunotherapies I've had, IL-2, TIL, and ipi, my doctor at my home hospital, my doctors at NIH, and others we've spoken with believe the good response I've had has been because of the TIL. But stuff has crept through, notably a stretch of five different  mets in three different long bones (tibia and femur) of my legs that didn't respond while the others were literally melting away. More than once, my doctors have used the terms "safe haven" and "safe harbor" when describing what my melanoma was doing in the bones. There isn't a clear clinical reason why that would be, it's not as if there aren't blood vessels in the bones (they're actually dense with blood vessels) that would prevent TILs or other systemic treatments from reaching these mets.

My doctor also mentioned to me that he was at a recent melanoma conference and was discussing my case with Dr. O'Day (BH Cancer Center, was at Angeles, I think?) and that this indeed is something they're seeing more of — not necessarily always bone, but good responses tempered with a low burden of mets that don't seem to respond, but also aren't terribly aggressive. 

The strategy that's worked for us and O'Day said they've used has been to manage these with the traditional treatments of surgery or radiation as appropriate. We've taken to calling it "spot welding" — I've come to feel like I'm being held together by those welds and a maybe also a few rolls of duct tape, it really completes the image 😉

A good example is the lung met I had. Found on my regular PET last October and relatively small at 1.2-cm. But going back to three-month PETs to as early as the previous January, it was there, with slight growth from scan to scan. Knowing the nature of PET, I don't view it as something "they missed", if you go looking too hard at PET for every little thing, you'll find something and this clearly wasn't acting aggressive. So in October, even then it was a case of, "Yes, given your history, this is likely melanoma, but let's watch it a little first." First reaction is, "Get it out now!" but we went ahead and did a CT at six weeks and it looked relatively stable. Another six weeks and my regular PET came up again, the size was maybe 1.3-cm, not significant considering the CT part of PET-CT is lower power/resolution, but the SUV (metabolic brightness) had gone up some. Again, not terribly aggressive, but something that would need taken care if at some point.

So at that point just this past January, it seemed like wasting a bullet to try BRAF or a BRAF/MEK combo or look at a PD-1 trial. Save those for if or when I need them. We could have waited and watched more. It wasn't going to go away on its own, but it wasn't causing issues, wasn't going to be a source of more mets (which I've always found interesting), and was asymptomatic. But after talking with my radiation oncologist, all agreed that we had a good opportunity for more "spot welding". Everything else was relatively quiet, so let's just take the opportunity to knock it out now when there are no other complicating factors. 5 sessions of SBRT (radiation) over two weeks in February. In the April PET it was already smaller and dimmer and in my PET last week, it didn't even make the radiology report. I've posted elsewhere here about the effective use of radiation, but for us it's been a part of managing my disease and more and more, sounds like it is a part of the strategy for others. As scary as my brain met was, I include it in this whole thing, too. One met, sort of out of the blue, with the biggest difference being that the location requires that it be treated in much more quickly.

Long story short, though, these "rogue tumors" are becoming a common theme for some, but there are management strategies for them — an issue for us "near-NEDs", "pseudo-NEDs", or whatever you want to call us, and others who are having good responses to immunotherapies.

Joe

Brian,

   I'm not sure if I'm going to explain this right, but Dr. Kirkwood said its possible that the one tumor not responding doesn't have the PD1 receptor. Dr. Sznol at Yale wrote a paper on nivolumbab that sometimes it can progress like ipi then get better or it can have mixed results. You are excellent at finding papers so if you do, can you post it? It would be hopeful to all patients like my husband who are on PD1 drugs. In fact, we used the paper to argue to stay on the trial. Bill is feeling great and working full time. At the next scan( 6 weeks) we will decide whether to have VATS surgery or radiation on the one lung nodule. His anemia is fine. His hemoglobin has been in the 11-12 range for four months. Thank you Brian and Joe for all you do for this site!! You provide very important information in a very encouraging and caring way!

Maureen

Brian,

   I'm not sure if I'm going to explain this right, but Dr. Kirkwood said its possible that the one tumor not responding doesn't have the PD1 receptor. Dr. Sznol at Yale wrote a paper on nivolumbab that sometimes it can progress like ipi then get better or it can have mixed results. You are excellent at finding papers so if you do, can you post it? It would be hopeful to all patients like my husband who are on PD1 drugs. In fact, we used the paper to argue to stay on the trial. Bill is feeling great and working full time. At the next scan( 6 weeks) we will decide whether to have VATS surgery or radiation on the one lung nodule. His anemia is fine. His hemoglobin has been in the 11-12 range for four months. Thank you Brian and Joe for all you do for this site!! You provide very important information in a very encouraging and caring way!

Maureen

Yes he said he could stay on trial with the VATS surgery. I'm not sure about the radiation. We will be in Pittsburg on Monday and we will ask that question.

Maureen

Yes he said he could stay on trial with the VATS surgery. I'm not sure about the radiation. We will be in Pittsburg on Monday and we will ask that question.

Maureen

Yes he said he could stay on trial with the VATS surgery. I'm not sure about the radiation. We will be in Pittsburg on Monday and we will ask that question.

Maureen

Brian,

  We were just in Pittsburg on monday and found out that if the one nodule keeps growing that Bill can have the VATS surgery and it won't interfere at all with the trial unless there are complications with the surgery. Radiation would take him out of the study so we obviously would not chose to do that.

Maureen

Brian, 

    To further update you, I just found out another man on the same trial who has mucosal melanoma will have a one time radiation on a spot in his chest that keeps growing. All of his other areas of disease are stable or shrinking. It took until his tenth infusion of nivolumbab to see any shrinkage. I think melanoma specialists are going to have to be patient with nivolumbab because some patients take time. I shudder to think if we hadn't effectively argued with our doctor where we would be. Keep making this topic on the board so we can all learn from each other. Thanks for all you do!

Maureen

Brian, 

    To further update you, I just found out another man on the same trial who has mucosal melanoma will have a one time radiation on a spot in his chest that keeps growing. All of his other areas of disease are stable or shrinking. It took until his tenth infusion of nivolumbab to see any shrinkage. I think melanoma specialists are going to have to be patient with nivolumbab because some patients take time. I shudder to think if we hadn't effectively argued with our doctor where we would be. Keep making this topic on the board so we can all learn from each other. Thanks for all you do!

Maureen

Brian, 

    To further update you, I just found out another man on the same trial who has mucosal melanoma will have a one time radiation on a spot in his chest that keeps growing. All of his other areas of disease are stable or shrinking. It took until his tenth infusion of nivolumbab to see any shrinkage. I think melanoma specialists are going to have to be patient with nivolumbab because some patients take time. I shudder to think if we hadn't effectively argued with our doctor where we would be. Keep making this topic on the board so we can all learn from each other. Thanks for all you do!

Maureen

Brian,

  We were just in Pittsburg on monday and found out that if the one nodule keeps growing that Bill can have the VATS surgery and it won't interfere at all with the trial unless there are complications with the surgery. Radiation would take him out of the study so we obviously would not chose to do that.

Maureen

Brian,

  We were just in Pittsburg on monday and found out that if the one nodule keeps growing that Bill can have the VATS surgery and it won't interfere at all with the trial unless there are complications with the surgery. Radiation would take him out of the study so we obviously would not chose to do that.

Maureen

Nivolumab Induces Durable Response Rates and Overall Survival in Advanced Melanoma

Contributors: Anna Azvolinsky, PhD, Anne Jacobson, MPH, CCMEP, CMPP

Treatment with nivolumab, an investigational antibody targeting the programmed cell death protein 1 (PD-1), resulted in rapid and durable responses and prolonged overall survival in patients with metastatic melanoma, according to updated results from an ongoing phase I study. These findings lend additional support to the emerging role of PD-1 targeted immunotherapy in the treatment of melanoma and other solid tumors. 

Mario Sznol, MD, from the Yale Cancer Center in New Haven, Connecticut, presented results from the phase I trial at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.

Nivolumab joins ipilimumab, an anti-CTLA4 antibody, in the class of immunotherapeutic agents known as immune-checkpoint inhibitors. Both agents boost the antitumor activity of T cells by blocking pathways that normally dampen the T cell response. Ipilimumab is currently approved for the treatment of metastatic melanoma, having shown a response rate of approximately 10% and a 2-year overall survival rate of approximately 24% in pretreated patients.

The current trial enrolled 107 patients with metastatic melanoma. The median patient age was 61 years (range, 29 to 85 years). At baseline, 36% of patients had elevated lactate dehydrogenase levels, and 78% had visceral metastases. In the heavily pretreated study cohort, 66% of patients had received two or more prior therapies. Among the 25% of patients who had received at least three prior therapies, 65% received chemotherapy, 46% received any interleukin-2 inhibitor, and 5% had received a BRAF inhibitor. Patients were not permitted to have any prior treatment with immunosuppressive agents or T-cell targeted therapies.

All patients received treatment with IV nivolumab in various dosing cohorts (0.1, 0.3, 1, 3, and 10 mg/kg) every two weeks for up to 96 weeks. Across all dosage groups, the overall response rate was 31%, with 33 of 107 patients achieving complete or partial response. Responses were durable, with a median duration of response of 104 weeks. 

The kinetics of nivolumab response were atypical. While some patients had a rapid response, as early as eight weeks into therapy, “some patients may have new tumors or growth of existing tumors before developing a meaningful response,” Dr. Sznol said. Patients also continued to respond even after nivolumab was discontinued.

The most favorable responses were observed in the 3 mg/kg dosing group (n = 17). In this group, the overall response rate was 41%, and the median duration of response was 75 days. The median overall survival for patients in the 3 mg/kg dosing group was 20.3 months. Nivolumab 3 mg/kg every two weeks has been chosen as the preferred dose for additional evaluation in ongoing phase III trials.

For all patients, the median overall survival was 16.8 months, with 1-year and 2-year survival rates of 62% and 43%, respectively. Median progression-free survival was 3.7 months, with 1-year and 2-year progression-free survival rates of 36% and 27%, respectively.

Nivolumab was associated with a favorable toxicity profile. After at least one year of follow-up, 58% of patients reported adverse events of any grade with potential immunologic etiologies, including skin toxicity (38%), gastrointestinal symptoms (19%), and endocrinopathies (14%). Five patients (5%) reported any grade 3-4 immunologic toxicity.

“There is no question that nivolumab appears to have much less in the way of toxicity compared to ipilimumab,” said Dr. Sznol.

Oncologists are enthusiastic about the phase I results of nivolumab in metastatic melanoma. “These more mature data clearly indicate the high activity and efficacy of this drug and favorable side-effect profile,” said Nikhil Khushalani, MD, associate professor of oncology, at the Roswell Park Cancer Institute in Buffalo, New York, who was not associated with the study. Dr. Khushalani noted that the survival rate with nivolumab is remarkable—nearly double that of the historical data for ipilimumab. Monitoring patients for potentially severe immune-related effects will be crucial, Dr. Khushalani noted.

Nivolumab is currently under evaluation in three phase III clinical trials in patients with previously treated or treatment-naïve metastatic melanoma. According to Dr. Sznol, nivolumab has the potential for expanded uses and indications. “I think it is wrong to look at nivolumab just as a single agent. I think it can be used in different [tumor types] and the combinations [with other agents] will have lots of promise. This is just the beginning.”

Reference

Sznol M et al. “Survival and long-term follow-up of safety and response in patients (pts) with advanced melanoma (MEL) in a phase I trial of nivolumab” ASCO 2013 annual meeting abstract CRA9006.
http://meetinglibrary.asco.org/content/113607-132

Nivolumab Induces Durable Response Rates and Overall Survival in Advanced Melanoma

Contributors: Anna Azvolinsky, PhD, Anne Jacobson, MPH, CCMEP, CMPP

Treatment with nivolumab, an investigational antibody targeting the programmed cell death protein 1 (PD-1), resulted in rapid and durable responses and prolonged overall survival in patients with metastatic melanoma, according to updated results from an ongoing phase I study. These findings lend additional support to the emerging role of PD-1 targeted immunotherapy in the treatment of melanoma and other solid tumors. 

Mario Sznol, MD, from the Yale Cancer Center in New Haven, Connecticut, presented results from the phase I trial at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.

Nivolumab joins ipilimumab, an anti-CTLA4 antibody, in the class of immunotherapeutic agents known as immune-checkpoint inhibitors. Both agents boost the antitumor activity of T cells by blocking pathways that normally dampen the T cell response. Ipilimumab is currently approved for the treatment of metastatic melanoma, having shown a response rate of approximately 10% and a 2-year overall survival rate of approximately 24% in pretreated patients.

The current trial enrolled 107 patients with metastatic melanoma. The median patient age was 61 years (range, 29 to 85 years). At baseline, 36% of patients had elevated lactate dehydrogenase levels, and 78% had visceral metastases. In the heavily pretreated study cohort, 66% of patients had received two or more prior therapies. Among the 25% of patients who had received at least three prior therapies, 65% received chemotherapy, 46% received any interleukin-2 inhibitor, and 5% had received a BRAF inhibitor. Patients were not permitted to have any prior treatment with immunosuppressive agents or T-cell targeted therapies.

All patients received treatment with IV nivolumab in various dosing cohorts (0.1, 0.3, 1, 3, and 10 mg/kg) every two weeks for up to 96 weeks. Across all dosage groups, the overall response rate was 31%, with 33 of 107 patients achieving complete or partial response. Responses were durable, with a median duration of response of 104 weeks. 

The kinetics of nivolumab response were atypical. While some patients had a rapid response, as early as eight weeks into therapy, “some patients may have new tumors or growth of existing tumors before developing a meaningful response,” Dr. Sznol said. Patients also continued to respond even after nivolumab was discontinued.

The most favorable responses were observed in the 3 mg/kg dosing group (n = 17). In this group, the overall response rate was 41%, and the median duration of response was 75 days. The median overall survival for patients in the 3 mg/kg dosing group was 20.3 months. Nivolumab 3 mg/kg every two weeks has been chosen as the preferred dose for additional evaluation in ongoing phase III trials.

For all patients, the median overall survival was 16.8 months, with 1-year and 2-year survival rates of 62% and 43%, respectively. Median progression-free survival was 3.7 months, with 1-year and 2-year progression-free survival rates of 36% and 27%, respectively.

Nivolumab was associated with a favorable toxicity profile. After at least one year of follow-up, 58% of patients reported adverse events of any grade with potential immunologic etiologies, including skin toxicity (38%), gastrointestinal symptoms (19%), and endocrinopathies (14%). Five patients (5%) reported any grade 3-4 immunologic toxicity.

“There is no question that nivolumab appears to have much less in the way of toxicity compared to ipilimumab,” said Dr. Sznol.

Oncologists are enthusiastic about the phase I results of nivolumab in metastatic melanoma. “These more mature data clearly indicate the high activity and efficacy of this drug and favorable side-effect profile,” said Nikhil Khushalani, MD, associate professor of oncology, at the Roswell Park Cancer Institute in Buffalo, New York, who was not associated with the study. Dr. Khushalani noted that the survival rate with nivolumab is remarkable—nearly double that of the historical data for ipilimumab. Monitoring patients for potentially severe immune-related effects will be crucial, Dr. Khushalani noted.

Nivolumab is currently under evaluation in three phase III clinical trials in patients with previously treated or treatment-naïve metastatic melanoma. According to Dr. Sznol, nivolumab has the potential for expanded uses and indications. “I think it is wrong to look at nivolumab just as a single agent. I think it can be used in different [tumor types] and the combinations [with other agents] will have lots of promise. This is just the beginning.”

Reference

Sznol M et al. “Survival and long-term follow-up of safety and response in patients (pts) with advanced melanoma (MEL) in a phase I trial of nivolumab” ASCO 2013 annual meeting abstract CRA9006.
http://meetinglibrary.asco.org/content/113607-132

Nivolumab Induces Durable Response Rates and Overall Survival in Advanced Melanoma

Contributors: Anna Azvolinsky, PhD, Anne Jacobson, MPH, CCMEP, CMPP

Treatment with nivolumab, an investigational antibody targeting the programmed cell death protein 1 (PD-1), resulted in rapid and durable responses and prolonged overall survival in patients with metastatic melanoma, according to updated results from an ongoing phase I study. These findings lend additional support to the emerging role of PD-1 targeted immunotherapy in the treatment of melanoma and other solid tumors. 

Mario Sznol, MD, from the Yale Cancer Center in New Haven, Connecticut, presented results from the phase I trial at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.

Nivolumab joins ipilimumab, an anti-CTLA4 antibody, in the class of immunotherapeutic agents known as immune-checkpoint inhibitors. Both agents boost the antitumor activity of T cells by blocking pathways that normally dampen the T cell response. Ipilimumab is currently approved for the treatment of metastatic melanoma, having shown a response rate of approximately 10% and a 2-year overall survival rate of approximately 24% in pretreated patients.

The current trial enrolled 107 patients with metastatic melanoma. The median patient age was 61 years (range, 29 to 85 years). At baseline, 36% of patients had elevated lactate dehydrogenase levels, and 78% had visceral metastases. In the heavily pretreated study cohort, 66% of patients had received two or more prior therapies. Among the 25% of patients who had received at least three prior therapies, 65% received chemotherapy, 46% received any interleukin-2 inhibitor, and 5% had received a BRAF inhibitor. Patients were not permitted to have any prior treatment with immunosuppressive agents or T-cell targeted therapies.

All patients received treatment with IV nivolumab in various dosing cohorts (0.1, 0.3, 1, 3, and 10 mg/kg) every two weeks for up to 96 weeks. Across all dosage groups, the overall response rate was 31%, with 33 of 107 patients achieving complete or partial response. Responses were durable, with a median duration of response of 104 weeks. 

The kinetics of nivolumab response were atypical. While some patients had a rapid response, as early as eight weeks into therapy, “some patients may have new tumors or growth of existing tumors before developing a meaningful response,” Dr. Sznol said. Patients also continued to respond even after nivolumab was discontinued.

The most favorable responses were observed in the 3 mg/kg dosing group (n = 17). In this group, the overall response rate was 41%, and the median duration of response was 75 days. The median overall survival for patients in the 3 mg/kg dosing group was 20.3 months. Nivolumab 3 mg/kg every two weeks has been chosen as the preferred dose for additional evaluation in ongoing phase III trials.

For all patients, the median overall survival was 16.8 months, with 1-year and 2-year survival rates of 62% and 43%, respectively. Median progression-free survival was 3.7 months, with 1-year and 2-year progression-free survival rates of 36% and 27%, respectively.

Nivolumab was associated with a favorable toxicity profile. After at least one year of follow-up, 58% of patients reported adverse events of any grade with potential immunologic etiologies, including skin toxicity (38%), gastrointestinal symptoms (19%), and endocrinopathies (14%). Five patients (5%) reported any grade 3-4 immunologic toxicity.

“There is no question that nivolumab appears to have much less in the way of toxicity compared to ipilimumab,” said Dr. Sznol.

Oncologists are enthusiastic about the phase I results of nivolumab in metastatic melanoma. “These more mature data clearly indicate the high activity and efficacy of this drug and favorable side-effect profile,” said Nikhil Khushalani, MD, associate professor of oncology, at the Roswell Park Cancer Institute in Buffalo, New York, who was not associated with the study. Dr. Khushalani noted that the survival rate with nivolumab is remarkable—nearly double that of the historical data for ipilimumab. Monitoring patients for potentially severe immune-related effects will be crucial, Dr. Khushalani noted.

Nivolumab is currently under evaluation in three phase III clinical trials in patients with previously treated or treatment-naïve metastatic melanoma. According to Dr. Sznol, nivolumab has the potential for expanded uses and indications. “I think it is wrong to look at nivolumab just as a single agent. I think it can be used in different [tumor types] and the combinations [with other agents] will have lots of promise. This is just the beginning.”

Reference

Sznol M et al. “Survival and long-term follow-up of safety and response in patients (pts) with advanced melanoma (MEL) in a phase I trial of nivolumab” ASCO 2013 annual meeting abstract CRA9006.
http://meetinglibrary.asco.org/content/113607-132

Thank you to Kylez for posting this paper on MIF!!

Maureen

Thank you to Kylez for posting this paper on MIF!!

Maureen

Thank you to Kylez for posting this paper on MIF!!

Maureen

Brian,

   I'm not sure if I'm going to explain this right, but Dr. Kirkwood said its possible that the one tumor not responding doesn't have the PD1 receptor. Dr. Sznol at Yale wrote a paper on nivolumbab that sometimes it can progress like ipi then get better or it can have mixed results. You are excellent at finding papers so if you do, can you post it? It would be hopeful to all patients like my husband who are on PD1 drugs. In fact, we used the paper to argue to stay on the trial. Bill is feeling great and working full time. At the next scan( 6 weeks) we will decide whether to have VATS surgery or radiation on the one lung nodule. His anemia is fine. His hemoglobin has been in the 11-12 range for four months. Thank you Brian and Joe for all you do for this site!! You provide very important information in a very encouraging and caring way!

Maureen

Brian,

   There's another category of patients too. My husband is also on the ipi/nivo trial, but one lung nodule is not responding to the PD1, while the other eight have been stable for four months.My husband has had 50 percent shrinkage. Dr. Kirkwood said that that has happened to other patients too. Patient#1in Philly has the same issue of PD1 working on most tumors while not working on others. I also believe that his adernal gland has to be removed and it was a new tumor. Immunotherapy is going to bring about many categories of patients and hopefully many that are stable or NED.

Maureen

Interesting topic – I was entered into the BMS Ipi-Nivo trial in January after advancing to Stage  4 in November. My tumors (scalp, neck, lungs, vertebrae, legs) were very aggressive and growing/spreading rapidly. CT/PET after 12 weeks on the trial came back with no evidence of disease. My liver enzymes went up at that point and made me ineligible for continuation in the trial, but scans every 6 weeks since have been clear. I asked if my treatment could be unblinded, to see if I received Nivo, but this was not allowed. My oncologist is convinced I got Nivo since he had never seen such a rapid and complete response, especially with the tumor load I had.

Now it's watch and wait, trying not to be constantly looking over my shoulder and thinking every little thing I feel is another met.

I consider myself extremely lucky that I responded the way I did.

Interesting topic – I was entered into the BMS Ipi-Nivo trial in January after advancing to Stage  4 in November. My tumors (scalp, neck, lungs, vertebrae, legs) were very aggressive and growing/spreading rapidly. CT/PET after 12 weeks on the trial came back with no evidence of disease. My liver enzymes went up at that point and made me ineligible for continuation in the trial, but scans every 6 weeks since have been clear. I asked if my treatment could be unblinded, to see if I received Nivo, but this was not allowed. My oncologist is convinced I got Nivo since he had never seen such a rapid and complete response, especially with the tumor load I had.

Now it's watch and wait, trying not to be constantly looking over my shoulder and thinking every little thing I feel is another met.

I consider myself extremely lucky that I responded the way I did.

They will unblind me if I recurr and need further treatment. However, I cannot get further treatment through the trial.

They will unblind me if I recurr and need further treatment. However, I cannot get further treatment through the trial.

They will unblind me if I recurr and need further treatment. However, I cannot get further treatment through the trial.

Interesting topic – I was entered into the BMS Ipi-Nivo trial in January after advancing to Stage  4 in November. My tumors (scalp, neck, lungs, vertebrae, legs) were very aggressive and growing/spreading rapidly. CT/PET after 12 weeks on the trial came back with no evidence of disease. My liver enzymes went up at that point and made me ineligible for continuation in the trial, but scans every 6 weeks since have been clear. I asked if my treatment could be unblinded, to see if I received Nivo, but this was not allowed. My oncologist is convinced I got Nivo since he had never seen such a rapid and complete response, especially with the tumor load I had.

Now it's watch and wait, trying not to be constantly looking over my shoulder and thinking every little thing I feel is another met.

I consider myself extremely lucky that I responded the way I did.

My trial arm is the 1mg Ipi – 3 mg Nivo ( I believe this is the arm that had the second best response rate in the  original trial). No side effects worth mentioning ( I don't  consider the itching a side effect these days) except for one random trip to the emergency room ( Ipi reminding me who is boss).  I have been spot- welded with radiation to the femur and pelvis, which, I have been told, may have an additional synergistic effect with the immunotherapy . ( studies have proven this, but  you may need the odd resistant tumor to get the treatment while in the controlled trial environment)  I still limp a bit ( also not a side effect I care to complain about) For those in immunotherapy– induced stability,  my doctors believe that based on the studies to date:

 1) once the train has left the station — and you are responding,  it's unlikely you will progress back to the  level of tumor burden prior to treatment ( This is true for the 53 in the original trial– 17 still chugging along in various degrees of tumor reduction two years out).  Hence the discussion of chronic survival.

  2) based on past experience with Ipi– if you are a responder and your body needs a reminder, reintroduction of the Ipi will likely provide the same response. My doctor has patients going on seven years with Ipi alone– with adjustments like these.  Not a picnic but….

3) I heard one doctor theorize that it is the Ipi component of the treatment that imparts durability ( don't know where that comes from) 

In terms of spot welding–I used to own a Dodge Dart  with steering I likened to  hearding  cattle— perhaps I've become the vehicle, requiring constant adjustment. It would be nice to last as long!

My trial arm is the 1mg Ipi – 3 mg Nivo ( I believe this is the arm that had the second best response rate in the  original trial). No side effects worth mentioning ( I don't  consider the itching a side effect these days) except for one random trip to the emergency room ( Ipi reminding me who is boss).  I have been spot- welded with radiation to the femur and pelvis, which, I have been told, may have an additional synergistic effect with the immunotherapy . ( studies have proven this, but  you may need the odd resistant tumor to get the treatment while in the controlled trial environment)  I still limp a bit ( also not a side effect I care to complain about) For those in immunotherapy– induced stability,  my doctors believe that based on the studies to date:

 1) once the train has left the station — and you are responding,  it's unlikely you will progress back to the  level of tumor burden prior to treatment ( This is true for the 53 in the original trial– 17 still chugging along in various degrees of tumor reduction two years out).  Hence the discussion of chronic survival.

  2) based on past experience with Ipi– if you are a responder and your body needs a reminder, reintroduction of the Ipi will likely provide the same response. My doctor has patients going on seven years with Ipi alone– with adjustments like these.  Not a picnic but….

3) I heard one doctor theorize that it is the Ipi component of the treatment that imparts durability ( don't know where that comes from) 

In terms of spot welding–I used to own a Dodge Dart  with steering I likened to  hearding  cattle— perhaps I've become the vehicle, requiring constant adjustment. It would be nice to last as long!

My trial arm is the 1mg Ipi – 3 mg Nivo ( I believe this is the arm that had the second best response rate in the  original trial). No side effects worth mentioning ( I don't  consider the itching a side effect these days) except for one random trip to the emergency room ( Ipi reminding me who is boss).  I have been spot- welded with radiation to the femur and pelvis, which, I have been told, may have an additional synergistic effect with the immunotherapy . ( studies have proven this, but  you may need the odd resistant tumor to get the treatment while in the controlled trial environment)  I still limp a bit ( also not a side effect I care to complain about) For those in immunotherapy– induced stability,  my doctors believe that based on the studies to date:

 1) once the train has left the station — and you are responding,  it's unlikely you will progress back to the  level of tumor burden prior to treatment ( This is true for the 53 in the original trial– 17 still chugging along in various degrees of tumor reduction two years out).  Hence the discussion of chronic survival.

  2) based on past experience with Ipi– if you are a responder and your body needs a reminder, reintroduction of the Ipi will likely provide the same response. My doctor has patients going on seven years with Ipi alone– with adjustments like these.  Not a picnic but….

3) I heard one doctor theorize that it is the Ipi component of the treatment that imparts durability ( don't know where that comes from) 

In terms of spot welding–I used to own a Dodge Dart  with steering I likened to  hearding  cattle— perhaps I've become the vehicle, requiring constant adjustment. It would be nice to last as long!

BUT Joe, "You look so well."  how can you relly be sick?  Welcome to where we don't want to be. Evenif you are as long winded as I tend to be!  (Stage IV since at  least Feb 2007 and never NED in this time.)

BUT Joe, "You look so well."  how can you relly be sick?  Welcome to where we don't want to be. Evenif you are as long winded as I tend to be!  (Stage IV since at  least Feb 2007 and never NED in this time.)

BUT Joe, "You look so well."  how can you relly be sick?  Welcome to where we don't want to be. Evenif you are as long winded as I tend to be!  (Stage IV since at  least Feb 2007 and never NED in this time.)

Thanks Ed.  As you can tell, brevity isn't my strong suit, but in individual interactions I do try to keep it simple. I have a private CaringBridge blog where I'm more detailed, and that's a challenge, keep it simple and people don't understand and too detailed and people start to zone out — not a criticism, just human nature.  I am glad I've started to be more active here because there is a group who understands.  Joe

The hardest part is that people do care.  But, as many have written, they simply don't get it.  

At work I actually wrote a staff e-mail and told people that I am sick of talking about it (stage IV since Sept 2011).  I told them to PLEASE not say, "Let me know how I can help"…"How do you feel?" …. "How are you doing?" …. "Tell me if you need anything."…  Several people actually thanked me for writing the e-mail because they felt 'different' around me and were not sure how to act.  I told everyone that the more they make fun of me, tease me (as they always did) the better I feel.  I tend to be a private person so that worked for me.  I've talked to other people with melanoma who feel good when people talk to them.  I think it's most important for us to be clear about our expectaions and talk to family and friends about it.

Also, after many surgeries, ER visits, treatments, etc., I am now blunt and to the point – living in Philadelphia helps- people here expect that anyway!  As for surgeries I say the following:

 I am tired in the hospital-please don't visit

Please don't visit my home immediately after because I will be in pain (or hopped up on decadron).  

If you'd really like to help… drop off a meal in a dish I don't need to return. Get my wife a message. Mow my lawn.  Take out my trash … Babysit, babysit, babysit …

Good luck everyone.  Thanks for sharing.

Brendan

The hardest part is that people do care.  But, as many have written, they simply don't get it.  

At work I actually wrote a staff e-mail and told people that I am sick of talking about it (stage IV since Sept 2011).  I told them to PLEASE not say, "Let me know how I can help"…"How do you feel?" …. "How are you doing?" …. "Tell me if you need anything."…  Several people actually thanked me for writing the e-mail because they felt 'different' around me and were not sure how to act.  I told everyone that the more they make fun of me, tease me (as they always did) the better I feel.  I tend to be a private person so that worked for me.  I've talked to other people with melanoma who feel good when people talk to them.  I think it's most important for us to be clear about our expectaions and talk to family and friends about it.

Also, after many surgeries, ER visits, treatments, etc., I am now blunt and to the point – living in Philadelphia helps- people here expect that anyway!  As for surgeries I say the following:

 I am tired in the hospital-please don't visit

Please don't visit my home immediately after because I will be in pain (or hopped up on decadron).  

If you'd really like to help… drop off a meal in a dish I don't need to return. Get my wife a message. Mow my lawn.  Take out my trash … Babysit, babysit, babysit …

Good luck everyone.  Thanks for sharing.

Brendan

The hardest part is that people do care.  But, as many have written, they simply don't get it.  

At work I actually wrote a staff e-mail and told people that I am sick of talking about it (stage IV since Sept 2011).  I told them to PLEASE not say, "Let me know how I can help"…"How do you feel?" …. "How are you doing?" …. "Tell me if you need anything."…  Several people actually thanked me for writing the e-mail because they felt 'different' around me and were not sure how to act.  I told everyone that the more they make fun of me, tease me (as they always did) the better I feel.  I tend to be a private person so that worked for me.  I've talked to other people with melanoma who feel good when people talk to them.  I think it's most important for us to be clear about our expectaions and talk to family and friends about it.

Also, after many surgeries, ER visits, treatments, etc., I am now blunt and to the point – living in Philadelphia helps- people here expect that anyway!  As for surgeries I say the following:

 I am tired in the hospital-please don't visit

Please don't visit my home immediately after because I will be in pain (or hopped up on decadron).  

If you'd really like to help… drop off a meal in a dish I don't need to return. Get my wife a message. Mow my lawn.  Take out my trash … Babysit, babysit, babysit …

Good luck everyone.  Thanks for sharing.

Brendan

Thanks Ed.  As you can tell, brevity isn't my strong suit, but in individual interactions I do try to keep it simple. I have a private CaringBridge blog where I'm more detailed, and that's a challenge, keep it simple and people don't understand and too detailed and people start to zone out — not a criticism, just human nature.  I am glad I've started to be more active here because there is a group who understands.  Joe

Thanks Ed.  As you can tell, brevity isn't my strong suit, but in individual interactions I do try to keep it simple. I have a private CaringBridge blog where I'm more detailed, and that's a challenge, keep it simple and people don't understand and too detailed and people start to zone out — not a criticism, just human nature.  I am glad I've started to be more active here because there is a group who understands.  Joe