Brain Mets and Yervoy Success?

Dear Alex,

Sorry that you and your father are dealing with this. I have not taken Yervoy, below are articles that indicate ipi can be helpful in brain mets.

From:  Novel Treatments for Melanoma Brain Metastases
Kenchappa, Tran, Rao, Smalley, Gibney, Sondak, and Forsyth. October 2013.  Cancer Control.

"Ipilimumab:
Another strategy that has changed the treatment of melanoma is the use of drugs to upregulate T-cell function using antibodies to block the cytotoxic T-lymphocyte antigen (CTLA)4, which potentiates antitumor immune responses.  Ipi, the anti-CTLA-4 monoclonal antibody, prolonged overall survival rates in patients with metastatic mel in two phase III studies. Although traditional radiographic responses were seen in a small percentage of patients (10-15%), many of these responses lasted months to years.  These first pivotal studies excluded patients with MBMs. [Later studies using ipi in brain mets showed that patients with asymptomatic brain mets and NOT on corticosteroids had a 25% rate of disease control, while symptomatic patients with MBMs currently taking corticosteroids had a 10% rate of control.]  …this study revealed that ipi has activity in MBMs…it is unknown whether the treatment was more effective in larger MBMs in which the highly permeable BBB may allow a greater ingress of activated cytotoxic T cells.

     …Patience…[in monitoring clinical benefit] is required when using immunotherapies.  Early in the course of treatment, lesions may grow and become symptomatic, which is a pattern seen in systemic melanoma lesions treated with ipi, even though significant clinical response will ultimately occur.  In general, we attempt to wait until the end of the induction phase of ipi before concluding the presence of progressive disease.

The concept of delayed response – for example, with ipi – is important to avoid discontinuing the drug too early because of changes in volume enhancement unrelated to tumor growth…."

Link to entire article synopsis:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/02/overview-of-treatments-for-melanoma.html

A more recent article:

Phase II trial of ipi monotherapy in melanoma patients with brain metastases.
Authors: Lawrence, et al. 
"Ipilimumab, a human monoclonal antibody that blocks CTLA-4 has activity in advanced melanoma.  This phase II trial attempted to assess ipi safety and activity in melanoma patients with brain mets.  Patients had measurable brain mets with at least one lesion >0.5cm and/or 2 lesions greater than 0.3cm, and none greater than 3cm in diameter.  Prior whole brain or stereotactic radiation to non-index lesions were allowed.  Ipi 10mg/kg was given IV every 3 weeks for 4 doses.  Responding or stable patients could receive maintenance ipi at 10mg/kg every 12 weeks.  Total of 72 patients in two arms…arm B still ongoing.  No association between brain edema or cerebral hemorrhage and objective response.  Of 51 patients in Arm A, at week 12: 4/51 had a partial response, 5/51 had stable disease, with additional unconfirmed responses.  Duration of responses ranged from 3 to 12+ months and duration of stable disease ranged from 1-7 months.  CONCLUSION:  Ipi has a similar level of activity in brain and non-CNS lesions."  

I hope this helps.  Wishing you and your dad my best.  Celeste

Dear Alex,

Sorry that you and your father are dealing with this. I have not taken Yervoy, below are articles that indicate ipi can be helpful in brain mets.

From:  Novel Treatments for Melanoma Brain Metastases
Kenchappa, Tran, Rao, Smalley, Gibney, Sondak, and Forsyth. October 2013.  Cancer Control.

"Ipilimumab:
Another strategy that has changed the treatment of melanoma is the use of drugs to upregulate T-cell function using antibodies to block the cytotoxic T-lymphocyte antigen (CTLA)4, which potentiates antitumor immune responses.  Ipi, the anti-CTLA-4 monoclonal antibody, prolonged overall survival rates in patients with metastatic mel in two phase III studies. Although traditional radiographic responses were seen in a small percentage of patients (10-15%), many of these responses lasted months to years.  These first pivotal studies excluded patients with MBMs. [Later studies using ipi in brain mets showed that patients with asymptomatic brain mets and NOT on corticosteroids had a 25% rate of disease control, while symptomatic patients with MBMs currently taking corticosteroids had a 10% rate of control.]  …this study revealed that ipi has activity in MBMs…it is unknown whether the treatment was more effective in larger MBMs in which the highly permeable BBB may allow a greater ingress of activated cytotoxic T cells.

     …Patience…[in monitoring clinical benefit] is required when using immunotherapies.  Early in the course of treatment, lesions may grow and become symptomatic, which is a pattern seen in systemic melanoma lesions treated with ipi, even though significant clinical response will ultimately occur.  In general, we attempt to wait until the end of the induction phase of ipi before concluding the presence of progressive disease.

The concept of delayed response – for example, with ipi – is important to avoid discontinuing the drug too early because of changes in volume enhancement unrelated to tumor growth…."

Link to entire article synopsis:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/02/overview-of-treatments-for-melanoma.html

A more recent article:

Phase II trial of ipi monotherapy in melanoma patients with brain metastases.
Authors: Lawrence, et al. 
"Ipilimumab, a human monoclonal antibody that blocks CTLA-4 has activity in advanced melanoma.  This phase II trial attempted to assess ipi safety and activity in melanoma patients with brain mets.  Patients had measurable brain mets with at least one lesion >0.5cm and/or 2 lesions greater than 0.3cm, and none greater than 3cm in diameter.  Prior whole brain or stereotactic radiation to non-index lesions were allowed.  Ipi 10mg/kg was given IV every 3 weeks for 4 doses.  Responding or stable patients could receive maintenance ipi at 10mg/kg every 12 weeks.  Total of 72 patients in two arms…arm B still ongoing.  No association between brain edema or cerebral hemorrhage and objective response.  Of 51 patients in Arm A, at week 12: 4/51 had a partial response, 5/51 had stable disease, with additional unconfirmed responses.  Duration of responses ranged from 3 to 12+ months and duration of stable disease ranged from 1-7 months.  CONCLUSION:  Ipi has a similar level of activity in brain and non-CNS lesions."  

I hope this helps.  Wishing you and your dad my best.  Celeste

Dear Alex,

Sorry that you and your father are dealing with this. I have not taken Yervoy, below are articles that indicate ipi can be helpful in brain mets.

From:  Novel Treatments for Melanoma Brain Metastases
Kenchappa, Tran, Rao, Smalley, Gibney, Sondak, and Forsyth. October 2013.  Cancer Control.

"Ipilimumab:
Another strategy that has changed the treatment of melanoma is the use of drugs to upregulate T-cell function using antibodies to block the cytotoxic T-lymphocyte antigen (CTLA)4, which potentiates antitumor immune responses.  Ipi, the anti-CTLA-4 monoclonal antibody, prolonged overall survival rates in patients with metastatic mel in two phase III studies. Although traditional radiographic responses were seen in a small percentage of patients (10-15%), many of these responses lasted months to years.  These first pivotal studies excluded patients with MBMs. [Later studies using ipi in brain mets showed that patients with asymptomatic brain mets and NOT on corticosteroids had a 25% rate of disease control, while symptomatic patients with MBMs currently taking corticosteroids had a 10% rate of control.]  …this study revealed that ipi has activity in MBMs…it is unknown whether the treatment was more effective in larger MBMs in which the highly permeable BBB may allow a greater ingress of activated cytotoxic T cells.

     …Patience…[in monitoring clinical benefit] is required when using immunotherapies.  Early in the course of treatment, lesions may grow and become symptomatic, which is a pattern seen in systemic melanoma lesions treated with ipi, even though significant clinical response will ultimately occur.  In general, we attempt to wait until the end of the induction phase of ipi before concluding the presence of progressive disease.

The concept of delayed response – for example, with ipi – is important to avoid discontinuing the drug too early because of changes in volume enhancement unrelated to tumor growth…."

Link to entire article synopsis:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/02/overview-of-treatments-for-melanoma.html

A more recent article:

Phase II trial of ipi monotherapy in melanoma patients with brain metastases.
Authors: Lawrence, et al. 
"Ipilimumab, a human monoclonal antibody that blocks CTLA-4 has activity in advanced melanoma.  This phase II trial attempted to assess ipi safety and activity in melanoma patients with brain mets.  Patients had measurable brain mets with at least one lesion >0.5cm and/or 2 lesions greater than 0.3cm, and none greater than 3cm in diameter.  Prior whole brain or stereotactic radiation to non-index lesions were allowed.  Ipi 10mg/kg was given IV every 3 weeks for 4 doses.  Responding or stable patients could receive maintenance ipi at 10mg/kg every 12 weeks.  Total of 72 patients in two arms…arm B still ongoing.  No association between brain edema or cerebral hemorrhage and objective response.  Of 51 patients in Arm A, at week 12: 4/51 had a partial response, 5/51 had stable disease, with additional unconfirmed responses.  Duration of responses ranged from 3 to 12+ months and duration of stable disease ranged from 1-7 months.  CONCLUSION:  Ipi has a similar level of activity in brain and non-CNS lesions."  

I hope this helps.  Wishing you and your dad my best.  Celeste

I did the standard fda 4 doses of Yervoy however at the time I did not have brain mets or at least not detectable.

Yervoy and all the immunotherapy medicines since they work with the immune system to produce an immune response are capable of getting through the brain barrier to fight the mel. However that is when they work. I was a non responder to Yervoy and currently trying pd1.

Best of luck to your father.

I did the standard fda 4 doses of Yervoy however at the time I did not have brain mets or at least not detectable.

Yervoy and all the immunotherapy medicines since they work with the immune system to produce an immune response are capable of getting through the brain barrier to fight the mel. However that is when they work. I was a non responder to Yervoy and currently trying pd1.

Best of luck to your father.

I did the standard fda 4 doses of Yervoy however at the time I did not have brain mets or at least not detectable.

Yervoy and all the immunotherapy medicines since they work with the immune system to produce an immune response are capable of getting through the brain barrier to fight the mel. However that is when they work. I was a non responder to Yervoy and currently trying pd1.

Best of luck to your father.

Hi,

My Mother was diagnosed with Stage IV in November of last year.  We discovered after a 3rd opinion on treatment that she had brain mets.  She had gamma knife and then started Yervoy 4 days later.  We choose Yervoy because it does had a positive retrospective analysis on patients who had brain mets and were treated with Yervoy. My Mom is BRAF positive and if she did not respond to Yervoy we were going to start with BRAF pills and try to get her into a compassionate use trial for the PD1's…. We haven't had to do this…

Her first gamma knife treatment was on December 9th.  Her first treatment of Yervoy was on December 12th. She has done amazingly well on Yervoy even though she had colitis and only 3 infusions. (1st 2 infusions were back to back with the last in March after "recovering" from coliits). 

The original brain mets treated are stable. However she had 16 new brain mets (discovered AFTER a 2nd opinion).  She was treated again with gamma knife radiation on April 15th.

She has had her 2 month follow up after treating the new brain mets and the first follow up after ending Yervoy.  All brain mets are stable and no new ones were found. Her next follow up is the first week of August. There is no loss of cognitive function and she's back to her normal activities except driving.

What I discovered throughout this process was to make sure that we got a 2nd or 3rd opinions.  Here is why:

1) The 3rd opinion from a melanoma specialist (we ended up seeing 4!) discovered the brain mets that the radiologist "overlooked".  

2) The Neuro-oncologist wasn't consulting with the radiologist who preformed the gamma knife surgery in December.  When we heard that she had a new 1mm tumor and that he wanted to wait and see what happened rather than taking action we sought another opinion.  Good thing we did, because there were multiple brain mets in her prefrontal lobe and the smaller brain mets that they had noticed in February were larger…

I've also learned that you need to make sure that you are working with a good team of doctors. In my Mom's case, she ended up seeing Dr. Eric Chang, at the Keck School of Medicine in Los Angeles (USC Los Angeles) for gamma knife treatment.  We are very grateful to have been able to have her seen by him and it was a relief to know how much experience he and his team had with treating brain mets with gamma knife radiation.  

In the last visit with her doctor (the awesome Dr. Mike Wong @ USC Los Angeles!) he said that Yervoy seems to affect brain mets later than it affects other tumors.  In my Mom's case, the tumors on her head and neck "disappeared" quickly. The 5 tumors in her trunk (lungs, kidney, liver, adrenal gland) have not grown and are stable or smaller.  Since your Dad does not have other tumors I would imagine that you would see results "faster".

If you have not conspired getting a second opinion from another doctor on treating the brain mets or know if your Dad is BRAF positive or not I would start making appointments now.  It made a huge difference in the outlook for my Mom.

PS

If your treating doctor is NOT a melanoma specialist please ensure that your next visit is with one. Lastly, there is a BRAF and MEK ihibitor combo that was just approved. This could be a good choice if your Dad is BRAF positive and Yervoy/gamma knife does not work.

Hi,

My Mother was diagnosed with Stage IV in November of last year.  We discovered after a 3rd opinion on treatment that she had brain mets.  She had gamma knife and then started Yervoy 4 days later.  We choose Yervoy because it does had a positive retrospective analysis on patients who had brain mets and were treated with Yervoy. My Mom is BRAF positive and if she did not respond to Yervoy we were going to start with BRAF pills and try to get her into a compassionate use trial for the PD1's…. We haven't had to do this…

Her first gamma knife treatment was on December 9th.  Her first treatment of Yervoy was on December 12th. She has done amazingly well on Yervoy even though she had colitis and only 3 infusions. (1st 2 infusions were back to back with the last in March after "recovering" from coliits). 

The original brain mets treated are stable. However she had 16 new brain mets (discovered AFTER a 2nd opinion).  She was treated again with gamma knife radiation on April 15th.

She has had her 2 month follow up after treating the new brain mets and the first follow up after ending Yervoy.  All brain mets are stable and no new ones were found. Her next follow up is the first week of August. There is no loss of cognitive function and she's back to her normal activities except driving.

What I discovered throughout this process was to make sure that we got a 2nd or 3rd opinions.  Here is why:

1) The 3rd opinion from a melanoma specialist (we ended up seeing 4!) discovered the brain mets that the radiologist "overlooked".  

2) The Neuro-oncologist wasn't consulting with the radiologist who preformed the gamma knife surgery in December.  When we heard that she had a new 1mm tumor and that he wanted to wait and see what happened rather than taking action we sought another opinion.  Good thing we did, because there were multiple brain mets in her prefrontal lobe and the smaller brain mets that they had noticed in February were larger…

I've also learned that you need to make sure that you are working with a good team of doctors. In my Mom's case, she ended up seeing Dr. Eric Chang, at the Keck School of Medicine in Los Angeles (USC Los Angeles) for gamma knife treatment.  We are very grateful to have been able to have her seen by him and it was a relief to know how much experience he and his team had with treating brain mets with gamma knife radiation.  

In the last visit with her doctor (the awesome Dr. Mike Wong @ USC Los Angeles!) he said that Yervoy seems to affect brain mets later than it affects other tumors.  In my Mom's case, the tumors on her head and neck "disappeared" quickly. The 5 tumors in her trunk (lungs, kidney, liver, adrenal gland) have not grown and are stable or smaller.  Since your Dad does not have other tumors I would imagine that you would see results "faster".

If you have not conspired getting a second opinion from another doctor on treating the brain mets or know if your Dad is BRAF positive or not I would start making appointments now.  It made a huge difference in the outlook for my Mom.

PS

If your treating doctor is NOT a melanoma specialist please ensure that your next visit is with one. Lastly, there is a BRAF and MEK ihibitor combo that was just approved. This could be a good choice if your Dad is BRAF positive and Yervoy/gamma knife does not work.

Hi,

My Mother was diagnosed with Stage IV in November of last year.  We discovered after a 3rd opinion on treatment that she had brain mets.  She had gamma knife and then started Yervoy 4 days later.  We choose Yervoy because it does had a positive retrospective analysis on patients who had brain mets and were treated with Yervoy. My Mom is BRAF positive and if she did not respond to Yervoy we were going to start with BRAF pills and try to get her into a compassionate use trial for the PD1's…. We haven't had to do this…

Her first gamma knife treatment was on December 9th.  Her first treatment of Yervoy was on December 12th. She has done amazingly well on Yervoy even though she had colitis and only 3 infusions. (1st 2 infusions were back to back with the last in March after "recovering" from coliits). 

The original brain mets treated are stable. However she had 16 new brain mets (discovered AFTER a 2nd opinion).  She was treated again with gamma knife radiation on April 15th.

She has had her 2 month follow up after treating the new brain mets and the first follow up after ending Yervoy.  All brain mets are stable and no new ones were found. Her next follow up is the first week of August. There is no loss of cognitive function and she's back to her normal activities except driving.

What I discovered throughout this process was to make sure that we got a 2nd or 3rd opinions.  Here is why:

1) The 3rd opinion from a melanoma specialist (we ended up seeing 4!) discovered the brain mets that the radiologist "overlooked".  

2) The Neuro-oncologist wasn't consulting with the radiologist who preformed the gamma knife surgery in December.  When we heard that she had a new 1mm tumor and that he wanted to wait and see what happened rather than taking action we sought another opinion.  Good thing we did, because there were multiple brain mets in her prefrontal lobe and the smaller brain mets that they had noticed in February were larger…

I've also learned that you need to make sure that you are working with a good team of doctors. In my Mom's case, she ended up seeing Dr. Eric Chang, at the Keck School of Medicine in Los Angeles (USC Los Angeles) for gamma knife treatment.  We are very grateful to have been able to have her seen by him and it was a relief to know how much experience he and his team had with treating brain mets with gamma knife radiation.  

In the last visit with her doctor (the awesome Dr. Mike Wong @ USC Los Angeles!) he said that Yervoy seems to affect brain mets later than it affects other tumors.  In my Mom's case, the tumors on her head and neck "disappeared" quickly. The 5 tumors in her trunk (lungs, kidney, liver, adrenal gland) have not grown and are stable or smaller.  Since your Dad does not have other tumors I would imagine that you would see results "faster".

If you have not conspired getting a second opinion from another doctor on treating the brain mets or know if your Dad is BRAF positive or not I would start making appointments now.  It made a huge difference in the outlook for my Mom.

PS

If your treating doctor is NOT a melanoma specialist please ensure that your next visit is with one. Lastly, there is a BRAF and MEK ihibitor combo that was just approved. This could be a good choice if your Dad is BRAF positive and Yervoy/gamma knife does not work.

It sounds like you are pretty far down the road with Yervoy but just for additional info. There is an anti pd-1 trial at Yale taking applications for people with brain mets. Dr Mario Sznoll was the Dr I had contacted and they put me in touch with the nurse taking information today. My recent tumor is between brain Derma and skull so not technically in/on the brain I am going the SDS route tomorrow morning. There isn't enough data with anti pd-1 and brain mets currently but with such strong results elsewhere in the body it is worth a hard look. As mentioned on an earlier post the blood brain barrier should not be an issue as its unlocking the bodies own defenses..I wish your Dad all the best.  Also you mention the headaches when standing. Perhaps these are related to the brain mets and not the Yervoy. I had brutal headaches when standing last August but they were immediately relieved post surgical resection on the tumor.  

It sounds like you are pretty far down the road with Yervoy but just for additional info. There is an anti pd-1 trial at Yale taking applications for people with brain mets. Dr Mario Sznoll was the Dr I had contacted and they put me in touch with the nurse taking information today. My recent tumor is between brain Derma and skull so not technically in/on the brain I am going the SDS route tomorrow morning. There isn't enough data with anti pd-1 and brain mets currently but with such strong results elsewhere in the body it is worth a hard look. As mentioned on an earlier post the blood brain barrier should not be an issue as its unlocking the bodies own defenses..I wish your Dad all the best.  Also you mention the headaches when standing. Perhaps these are related to the brain mets and not the Yervoy. I had brutal headaches when standing last August but they were immediately relieved post surgical resection on the tumor.  

It sounds like you are pretty far down the road with Yervoy but just for additional info. There is an anti pd-1 trial at Yale taking applications for people with brain mets. Dr Mario Sznoll was the Dr I had contacted and they put me in touch with the nurse taking information today. My recent tumor is between brain Derma and skull so not technically in/on the brain I am going the SDS route tomorrow morning. There isn't enough data with anti pd-1 and brain mets currently but with such strong results elsewhere in the body it is worth a hard look. As mentioned on an earlier post the blood brain barrier should not be an issue as its unlocking the bodies own defenses..I wish your Dad all the best.  Also you mention the headaches when standing. Perhaps these are related to the brain mets and not the Yervoy. I had brutal headaches when standing last August but they were immediately relieved post surgical resection on the tumor.