anti-PD 1 side effects and combo with MEK inhibitor?

So sorry for all that you and your husband are dealing with.  It is hard enough to have melanoma without feeling horribly ill as he does.  I don't really know enough about your husband's condition to answer you very well…but here are some things that I would think about and speak with his docs about:

As far as his side effects from ipi:  While he may not have had rashes and other more apparent things from his doses of ipi…..I am assuming that he certainly had side effects in the form of elevated liver functions such that it required cessation of the medication.  I am also assuming that is why he is on prednisone.  Ipi is well known for causing significant endocrine problems and that may be the cause for your husband's significant fatigue and even possibly the thrush….which can sometimes appear with adrenal suppression like in Addison's disease.  I would make sure (and his docs probably have!!) that his thyroid and adrenal function are being monitored.  Here's some information along those lines:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/03/melanoma-patients-teach-us-more-about.html

As far as expectations with anti-PD1:  Side effects and positive effects from anti-PD1 vary substantially from patient to patient, but are very similar between nivo and keytruda.  You can often see positive effects on tumors around 8-12 weeks of drug administration…though it can happen even later than that.  Side effects are generally milder than those created by ipi…though the same sort of effects can occur….including the endocrine ones.  Here is a description of typical side effects from anti-PD1:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2013/10/side-effects-of-nivolumab.html

NRAS and MEK:  The good news is that Binimetinib (MEK 162) is making a good showing in patients with NRAS-mutant melanoma.  NEMO is a Phase III trial that is ongoing.  Here is what some of the experts have had to say about that: 

http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/06/pretty-darn-impressivea-chat-between.html   Specifically, here is what Dr. Weber had to say on the topic in the above chat with Ribas:  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."

Here is a post I wrote last year when some of the MEK data was just coming out, before it was FDA approved.  The first bit of the post is probably most meaningful for your situation, but it may help you understand how it all works:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2013/01/better-news-for-mek-and-brafmek-combos.html

As far as taking anti-PD1 and MEK together……it makes sense for some. More and more combo's with greater numbers of patients using BRAF inhibitors and ipi or anti-PD1 are on the horizon or are just starting so more data will be coming in soon.  The general trend in what has been learned about these combos so far is that while they can be even more effective against melanoma than dosing with a single med….side effects can be increased, so you just have to be watchful about that.

Hope this helps.  Hang in there.  I wish you and your husband my best.  Celeste

So sorry for all that you and your husband are dealing with.  It is hard enough to have melanoma without feeling horribly ill as he does.  I don't really know enough about your husband's condition to answer you very well…but here are some things that I would think about and speak with his docs about:

As far as his side effects from ipi:  While he may not have had rashes and other more apparent things from his doses of ipi…..I am assuming that he certainly had side effects in the form of elevated liver functions such that it required cessation of the medication.  I am also assuming that is why he is on prednisone.  Ipi is well known for causing significant endocrine problems and that may be the cause for your husband's significant fatigue and even possibly the thrush….which can sometimes appear with adrenal suppression like in Addison's disease.  I would make sure (and his docs probably have!!) that his thyroid and adrenal function are being monitored.  Here's some information along those lines:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/03/melanoma-patients-teach-us-more-about.html

As far as expectations with anti-PD1:  Side effects and positive effects from anti-PD1 vary substantially from patient to patient, but are very similar between nivo and keytruda.  You can often see positive effects on tumors around 8-12 weeks of drug administration…though it can happen even later than that.  Side effects are generally milder than those created by ipi…though the same sort of effects can occur….including the endocrine ones.  Here is a description of typical side effects from anti-PD1:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2013/10/side-effects-of-nivolumab.html

NRAS and MEK:  The good news is that Binimetinib (MEK 162) is making a good showing in patients with NRAS-mutant melanoma.  NEMO is a Phase III trial that is ongoing.  Here is what some of the experts have had to say about that: 

http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/06/pretty-darn-impressivea-chat-between.html   Specifically, here is what Dr. Weber had to say on the topic in the above chat with Ribas:  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."

Here is a post I wrote last year when some of the MEK data was just coming out, before it was FDA approved.  The first bit of the post is probably most meaningful for your situation, but it may help you understand how it all works:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2013/01/better-news-for-mek-and-brafmek-combos.html

As far as taking anti-PD1 and MEK together……it makes sense for some. More and more combo's with greater numbers of patients using BRAF inhibitors and ipi or anti-PD1 are on the horizon or are just starting so more data will be coming in soon.  The general trend in what has been learned about these combos so far is that while they can be even more effective against melanoma than dosing with a single med….side effects can be increased, so you just have to be watchful about that.

Hope this helps.  Hang in there.  I wish you and your husband my best.  Celeste

So sorry for all that you and your husband are dealing with.  It is hard enough to have melanoma without feeling horribly ill as he does.  I don't really know enough about your husband's condition to answer you very well…but here are some things that I would think about and speak with his docs about:

As far as his side effects from ipi:  While he may not have had rashes and other more apparent things from his doses of ipi…..I am assuming that he certainly had side effects in the form of elevated liver functions such that it required cessation of the medication.  I am also assuming that is why he is on prednisone.  Ipi is well known for causing significant endocrine problems and that may be the cause for your husband's significant fatigue and even possibly the thrush….which can sometimes appear with adrenal suppression like in Addison's disease.  I would make sure (and his docs probably have!!) that his thyroid and adrenal function are being monitored.  Here's some information along those lines:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/03/melanoma-patients-teach-us-more-about.html

As far as expectations with anti-PD1:  Side effects and positive effects from anti-PD1 vary substantially from patient to patient, but are very similar between nivo and keytruda.  You can often see positive effects on tumors around 8-12 weeks of drug administration…though it can happen even later than that.  Side effects are generally milder than those created by ipi…though the same sort of effects can occur….including the endocrine ones.  Here is a description of typical side effects from anti-PD1:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2013/10/side-effects-of-nivolumab.html

NRAS and MEK:  The good news is that Binimetinib (MEK 162) is making a good showing in patients with NRAS-mutant melanoma.  NEMO is a Phase III trial that is ongoing.  Here is what some of the experts have had to say about that: 

http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/06/pretty-darn-impressivea-chat-between.html   Specifically, here is what Dr. Weber had to say on the topic in the above chat with Ribas:  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."

Here is a post I wrote last year when some of the MEK data was just coming out, before it was FDA approved.  The first bit of the post is probably most meaningful for your situation, but it may help you understand how it all works:  http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2013/01/better-news-for-mek-and-brafmek-combos.html

As far as taking anti-PD1 and MEK together……it makes sense for some. More and more combo's with greater numbers of patients using BRAF inhibitors and ipi or anti-PD1 are on the horizon or are just starting so more data will be coming in soon.  The general trend in what has been learned about these combos so far is that while they can be even more effective against melanoma than dosing with a single med….side effects can be increased, so you just have to be watchful about that.

Hope this helps.  Hang in there.  I wish you and your husband my best.  Celeste

Hi there cbe,

It looks like Celeste and Joe were quite helpful with their replies.  I don't think I am quite as helpful, but I noticed that your husband and I have some similarities…so I thought I would chime in.

I was 38 years old when diagnosed stage 4 (now I am 40.)  I too have the N-RAS mutation.  I also had melanoma in several lymph nodes all across my body and a mass on my liver.

I was put on Mercks MK-3475 (aka Pembro, aka Keytruda) right away (2 years ago.)  And I have not had any difficultly on this drug.  I've never been on any other treatment though, so I cannot speak to Ipi side effects.

My liver mass went away and most lymph nodes went back to normal after 3 months on MK-3475.  And the really aggressive node finally responded after 6 months on MK-3475, and is now back to almost a normal size. 

My side effects in that first 6 months on MK-3475 were nausea from time to time, fatigue somewhat, low grade temps in the 99's, and an itchy rash on my chest.  It wasn't so bad though.  I was able to work and live quite normally. 

I really hope it all balances out and it's just your body disliking the ipi and waiting for it to get out of your system.  Much health to you, Laurie

Hi there cbe,

It looks like Celeste and Joe were quite helpful with their replies.  I don't think I am quite as helpful, but I noticed that your husband and I have some similarities…so I thought I would chime in.

I was 38 years old when diagnosed stage 4 (now I am 40.)  I too have the N-RAS mutation.  I also had melanoma in several lymph nodes all across my body and a mass on my liver.

I was put on Mercks MK-3475 (aka Pembro, aka Keytruda) right away (2 years ago.)  And I have not had any difficultly on this drug.  I've never been on any other treatment though, so I cannot speak to Ipi side effects.

My liver mass went away and most lymph nodes went back to normal after 3 months on MK-3475.  And the really aggressive node finally responded after 6 months on MK-3475, and is now back to almost a normal size. 

My side effects in that first 6 months on MK-3475 were nausea from time to time, fatigue somewhat, low grade temps in the 99's, and an itchy rash on my chest.  It wasn't so bad though.  I was able to work and live quite normally. 

I really hope it all balances out and it's just your body disliking the ipi and waiting for it to get out of your system.  Much health to you, Laurie

Hi there cbe,

It looks like Celeste and Joe were quite helpful with their replies.  I don't think I am quite as helpful, but I noticed that your husband and I have some similarities…so I thought I would chime in.

I was 38 years old when diagnosed stage 4 (now I am 40.)  I too have the N-RAS mutation.  I also had melanoma in several lymph nodes all across my body and a mass on my liver.

I was put on Mercks MK-3475 (aka Pembro, aka Keytruda) right away (2 years ago.)  And I have not had any difficultly on this drug.  I've never been on any other treatment though, so I cannot speak to Ipi side effects.

My liver mass went away and most lymph nodes went back to normal after 3 months on MK-3475.  And the really aggressive node finally responded after 6 months on MK-3475, and is now back to almost a normal size. 

My side effects in that first 6 months on MK-3475 were nausea from time to time, fatigue somewhat, low grade temps in the 99's, and an itchy rash on my chest.  It wasn't so bad though.  I was able to work and live quite normally. 

I really hope it all balances out and it's just your body disliking the ipi and waiting for it to get out of your system.  Much health to you, Laurie