Stage 4 – Ipi, Zelboraf, Dab/Mek combo, and PD-1 all failed

Hi Sandy,

You have certainly been through the ringer.  I have not done IL-2, but many here have, with varying degrees of success. I am sure they will provide helpful advice.

However, the things that come to mind that I would be thinking about in your case are these:

1.  Anti-PDL1.  These trials are promising. Some are specifically for patients who have progressed on anti-PD1, especially since it was the last thing you took…they are actually seeking patients in your shoes to see if anti-PD1 followed by anti-PDL1 is helpful.

2.  TIL.  If I was going to end up taking IL-2, I'd probably look into doing it via TIL.  What the heck?  I think I'd just as soon go all the way if I were going to do that one.  Again, there are those here who have done that as well.  Getting in to a TIL program has a variety of requirements.  But, it may be worth your looking at.

3.  Intralesional therapy.  It's iffy.  There must be accessible lesions to inject.  But, some patients are having good results in that the injected tumor dies and in a fair number, "by-stander" lesions die as well.  At least worth asking about.

4.  Lots of the drugs you have already had are doing well in combo's.  Ipi is being combined with nivo, interferon, TVEC, IDO inhibitors, etc.  So are the anti-PD1 drugs.  Some trials may not allow you participation because of having had the drug you had, but some may.  Here is a brief list and description:

http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/09/weber-presentation-on-present-ipi.html

There are a few other options, but that's where I'd be looking if I were in your place.  There is info on my blog about the treatments I mentioned if you are interested.  Just use the search bubble on top left.  I wish you my best.  Hang in there.  Celeste

Hi Sandy,

You have certainly been through the ringer.  I have not done IL-2, but many here have, with varying degrees of success. I am sure they will provide helpful advice.

However, the things that come to mind that I would be thinking about in your case are these:

1.  Anti-PDL1.  These trials are promising. Some are specifically for patients who have progressed on anti-PD1, especially since it was the last thing you took…they are actually seeking patients in your shoes to see if anti-PD1 followed by anti-PDL1 is helpful.

2.  TIL.  If I was going to end up taking IL-2, I'd probably look into doing it via TIL.  What the heck?  I think I'd just as soon go all the way if I were going to do that one.  Again, there are those here who have done that as well.  Getting in to a TIL program has a variety of requirements.  But, it may be worth your looking at.

3.  Intralesional therapy.  It's iffy.  There must be accessible lesions to inject.  But, some patients are having good results in that the injected tumor dies and in a fair number, "by-stander" lesions die as well.  At least worth asking about.

4.  Lots of the drugs you have already had are doing well in combo's.  Ipi is being combined with nivo, interferon, TVEC, IDO inhibitors, etc.  So are the anti-PD1 drugs.  Some trials may not allow you participation because of having had the drug you had, but some may.  Here is a brief list and description:

http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/09/weber-presentation-on-present-ipi.html

There are a few other options, but that's where I'd be looking if I were in your place.  There is info on my blog about the treatments I mentioned if you are interested.  Just use the search bubble on top left.  I wish you my best.  Hang in there.  Celeste

Hi Sandy,

You have certainly been through the ringer.  I have not done IL-2, but many here have, with varying degrees of success. I am sure they will provide helpful advice.

However, the things that come to mind that I would be thinking about in your case are these:

1.  Anti-PDL1.  These trials are promising. Some are specifically for patients who have progressed on anti-PD1, especially since it was the last thing you took…they are actually seeking patients in your shoes to see if anti-PD1 followed by anti-PDL1 is helpful.

2.  TIL.  If I was going to end up taking IL-2, I'd probably look into doing it via TIL.  What the heck?  I think I'd just as soon go all the way if I were going to do that one.  Again, there are those here who have done that as well.  Getting in to a TIL program has a variety of requirements.  But, it may be worth your looking at.

3.  Intralesional therapy.  It's iffy.  There must be accessible lesions to inject.  But, some patients are having good results in that the injected tumor dies and in a fair number, "by-stander" lesions die as well.  At least worth asking about.

4.  Lots of the drugs you have already had are doing well in combo's.  Ipi is being combined with nivo, interferon, TVEC, IDO inhibitors, etc.  So are the anti-PD1 drugs.  Some trials may not allow you participation because of having had the drug you had, but some may.  Here is a brief list and description:

http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2014/09/weber-presentation-on-present-ipi.html

There are a few other options, but that's where I'd be looking if I were in your place.  There is info on my blog about the treatments I mentioned if you are interested.  Just use the search bubble on top left.  I wish you my best.  Hang in there.  Celeste

Wow Sandy. I am very sorry to hear your lack of success with the newer medicines. It reminds me of mine. Zel and ipi did nothing good for me. The taf/mek did keep most things from growing for a couple months. The huge difference though is finally I made it to keytruda pd-1 which has got me down to mild growth with stuff shrinking which is awesome.

I too went to Mayo in Rochester with Dr Kasi. He was talking about NCT02020707 abraxane. To quote my doc here in Saint Louis that is "old school". Mayo has great doc's and everything but when it comes to melanoma in my opinion they just aren't that much better than the fda approved meds.

You really need to get to one of the better places for melanoma. There is a Dr. Gajewsi at the University of Chicago. Not sure where you are coming from but it's only a couple hours or so from Mayo. They are big into immunotherapy. They are one of the 5 that Brystol Myers tries their stuff first. They apparently are very much into the better treatments out there. If my leg hadn't gone out on me I would have already been there and would know more. They do have the nivo (pd1) combined with anti-lag-3 NCT01968109 which if I read it right is basically for those who pd-1 on it's own didn't work. Also like the research nurse said they have several other things besides that.

Also like a recent post says on here UCLA has created an algorithm that predicts based on a tumor sample how a person will respond to the keytruda pd1. Apparently some places might be starting to be able to treat us based on what they see in our tumors. It may be worth a call to see what they have.

There is also Dr Wolchok at MSK in New York and Dr Weber at Tampa in Florida. Plus MD Anderson in Houston. Also Sarah Cannon in Nashville might have something.

I hesitate to mention Dr Rosenberg's TIL treatment at NIH in Bethesda Maryland. Apparently it can be very toxic and rough unless you are in pretty good health.

Also is wdvax NCT01753089 in boston but not sure of it's progress. It was certainly fantastic in mice but I haven't even heard rumors yet how it is doing in people and its been over a year.

Also might be some place with pdl but I haven't seen it yet nor antibody drug conjugates yet.

Hopefully others will know of more treatments but that is pretty much all I know and the better places to be if you can get there.

Good luck to you.

Artie

Wow Sandy. I am very sorry to hear your lack of success with the newer medicines. It reminds me of mine. Zel and ipi did nothing good for me. The taf/mek did keep most things from growing for a couple months. The huge difference though is finally I made it to keytruda pd-1 which has got me down to mild growth with stuff shrinking which is awesome.

I too went to Mayo in Rochester with Dr Kasi. He was talking about NCT02020707 abraxane. To quote my doc here in Saint Louis that is "old school". Mayo has great doc's and everything but when it comes to melanoma in my opinion they just aren't that much better than the fda approved meds.

You really need to get to one of the better places for melanoma. There is a Dr. Gajewsi at the University of Chicago. Not sure where you are coming from but it's only a couple hours or so from Mayo. They are big into immunotherapy. They are one of the 5 that Brystol Myers tries their stuff first. They apparently are very much into the better treatments out there. If my leg hadn't gone out on me I would have already been there and would know more. They do have the nivo (pd1) combined with anti-lag-3 NCT01968109 which if I read it right is basically for those who pd-1 on it's own didn't work. Also like the research nurse said they have several other things besides that.

Also like a recent post says on here UCLA has created an algorithm that predicts based on a tumor sample how a person will respond to the keytruda pd1. Apparently some places might be starting to be able to treat us based on what they see in our tumors. It may be worth a call to see what they have.

There is also Dr Wolchok at MSK in New York and Dr Weber at Tampa in Florida. Plus MD Anderson in Houston. Also Sarah Cannon in Nashville might have something.

I hesitate to mention Dr Rosenberg's TIL treatment at NIH in Bethesda Maryland. Apparently it can be very toxic and rough unless you are in pretty good health.

Also is wdvax NCT01753089 in boston but not sure of it's progress. It was certainly fantastic in mice but I haven't even heard rumors yet how it is doing in people and its been over a year.

Also might be some place with pdl but I haven't seen it yet nor antibody drug conjugates yet.

Hopefully others will know of more treatments but that is pretty much all I know and the better places to be if you can get there.

Good luck to you.

Artie

Wow Sandy. I am very sorry to hear your lack of success with the newer medicines. It reminds me of mine. Zel and ipi did nothing good for me. The taf/mek did keep most things from growing for a couple months. The huge difference though is finally I made it to keytruda pd-1 which has got me down to mild growth with stuff shrinking which is awesome.

I too went to Mayo in Rochester with Dr Kasi. He was talking about NCT02020707 abraxane. To quote my doc here in Saint Louis that is "old school". Mayo has great doc's and everything but when it comes to melanoma in my opinion they just aren't that much better than the fda approved meds.

You really need to get to one of the better places for melanoma. There is a Dr. Gajewsi at the University of Chicago. Not sure where you are coming from but it's only a couple hours or so from Mayo. They are big into immunotherapy. They are one of the 5 that Brystol Myers tries their stuff first. They apparently are very much into the better treatments out there. If my leg hadn't gone out on me I would have already been there and would know more. They do have the nivo (pd1) combined with anti-lag-3 NCT01968109 which if I read it right is basically for those who pd-1 on it's own didn't work. Also like the research nurse said they have several other things besides that.

Also like a recent post says on here UCLA has created an algorithm that predicts based on a tumor sample how a person will respond to the keytruda pd1. Apparently some places might be starting to be able to treat us based on what they see in our tumors. It may be worth a call to see what they have.

There is also Dr Wolchok at MSK in New York and Dr Weber at Tampa in Florida. Plus MD Anderson in Houston. Also Sarah Cannon in Nashville might have something.

I hesitate to mention Dr Rosenberg's TIL treatment at NIH in Bethesda Maryland. Apparently it can be very toxic and rough unless you are in pretty good health.

Also is wdvax NCT01753089 in boston but not sure of it's progress. It was certainly fantastic in mice but I haven't even heard rumors yet how it is doing in people and its been over a year.

Also might be some place with pdl but I haven't seen it yet nor antibody drug conjugates yet.

Hopefully others will know of more treatments but that is pretty much all I know and the better places to be if you can get there.

Good luck to you.

Artie

I'm so sorry you are having to deal with this awful disease again after 12 years of NED. How disheartening that must be. I'm sure you already have seen how much progress has been made in 12 years although your case shows there is still much to be done. I love, love, love what Art and Celeste posted. Your question about IL-2 experiences reminded me of Jerry's profile. He gave a very detailed account of his IL-2 treatment. 

http://www.melanoma.org/community/profiles/jerryfromfauq

As you can see it is a tough regimen but many say it was well worth it. I have seen a small trial combining SBRT and IL-2 that reported pretty good results that may be worth looking into. I wish you the best Sandy. Look forward to hearing your updates. 

Brian

I'm so sorry you are having to deal with this awful disease again after 12 years of NED. How disheartening that must be. I'm sure you already have seen how much progress has been made in 12 years although your case shows there is still much to be done. I love, love, love what Art and Celeste posted. Your question about IL-2 experiences reminded me of Jerry's profile. He gave a very detailed account of his IL-2 treatment. 

http://www.melanoma.org/community/profiles/jerryfromfauq

As you can see it is a tough regimen but many say it was well worth it. I have seen a small trial combining SBRT and IL-2 that reported pretty good results that may be worth looking into. I wish you the best Sandy. Look forward to hearing your updates. 

Brian

I'm so sorry you are having to deal with this awful disease again after 12 years of NED. How disheartening that must be. I'm sure you already have seen how much progress has been made in 12 years although your case shows there is still much to be done. I love, love, love what Art and Celeste posted. Your question about IL-2 experiences reminded me of Jerry's profile. He gave a very detailed account of his IL-2 treatment. 

http://www.melanoma.org/community/profiles/jerryfromfauq

As you can see it is a tough regimen but many say it was well worth it. I have seen a small trial combining SBRT and IL-2 that reported pretty good results that may be worth looking into. I wish you the best Sandy. Look forward to hearing your updates. 

Brian

Hi Sandy. Sorry to hear about nothing working real well, really hate hearing that from people. So I did combo of Ipi and Il-2 which it's been about a year since I finished ipi and Feb 2015 will be a year since I finished il-2. Unfortunately I can't tell you which drug worked or if both drugs worked. It put me at NED and hopefully I stay there. IL-2 was tough but doable…a previous poster mentioned Jerry. I definitely would read his info and reach out to him…he gave me a good snapshot of process and was right on. If your doc thinks this is way to go I'd consider it. Maybe with TIL….

Also Gajewski as Artie mentioned is well renowned for his immunotherapy work. I'm in Chicago but see Richards& Hallmeyer at Lutheran General. Very good with Mel and participate in trials etc…

wishing you the best!!

Josh

Hi Sandy. Sorry to hear about nothing working real well, really hate hearing that from people. So I did combo of Ipi and Il-2 which it's been about a year since I finished ipi and Feb 2015 will be a year since I finished il-2. Unfortunately I can't tell you which drug worked or if both drugs worked. It put me at NED and hopefully I stay there. IL-2 was tough but doable…a previous poster mentioned Jerry. I definitely would read his info and reach out to him…he gave me a good snapshot of process and was right on. If your doc thinks this is way to go I'd consider it. Maybe with TIL….

Also Gajewski as Artie mentioned is well renowned for his immunotherapy work. I'm in Chicago but see Richards& Hallmeyer at Lutheran General. Very good with Mel and participate in trials etc…

wishing you the best!!

Josh

Hi Sandy. Sorry to hear about nothing working real well, really hate hearing that from people. So I did combo of Ipi and Il-2 which it's been about a year since I finished ipi and Feb 2015 will be a year since I finished il-2. Unfortunately I can't tell you which drug worked or if both drugs worked. It put me at NED and hopefully I stay there. IL-2 was tough but doable…a previous poster mentioned Jerry. I definitely would read his info and reach out to him…he gave me a good snapshot of process and was right on. If your doc thinks this is way to go I'd consider it. Maybe with TIL….

Also Gajewski as Artie mentioned is well renowned for his immunotherapy work. I'm in Chicago but see Richards& Hallmeyer at Lutheran General. Very good with Mel and participate in trials etc…

wishing you the best!!

Josh

Hi, it's been quite a while since I've posted here myself (over a month, I think) and at the moment I am on PD-1 and it does seem to be working, but I did burn through Interferon, IL-2, Ipi (with WBR), and BRAF/MEK combo (along with 2 rounds of gamma knife plus a craniotomy) before I got here). 

I did IL-2 at Roswell Park Cancer Institute in Buffalo, NY under the care of Dr. Khushalani starting in December 2012 and completed 2 1/2 cycles (total 5 weeks). The 1/2 cycle was actually the first cycle as I developed severe colitis and was held in the hospital on fluid therapy for several extra days until that was resolved enough to make the trip home. The second week was cancelled and they weren't sure they wanted to let me come back, but I insisted (though I had to have a colonoscopy before they let me). After that they were very careful with my dosing and everything went as smoothly as it could have. They were also very cautious about health checks and making sure I was healthy enough to withstand the therapy in the first place. 

It is rough, but, like Interferon, it's a bit different for everyone. It was a bit different each week for me, but I think most people have similar side effects during each week. My main side effects were nausea/vomiting, fatigue, and low blood pressure (I normally have a low blood pressure so this made it even lower). There were a few doses that were skipped due to a slight rise in troponin (an indicator of cardiac stress), and I had a few instances of fever/severe chills, but it was not a predictable/regular side effect for me. I could not eat much of anything for most of the week I was there and every time I had significant colitis, though after the first week we (myself and my care team) were very careful and it was managed much better. I also gained roughly 15-20 pounds in fluid retention, which was all gone within 3-4 days of the last dose of the week. This fluid retention however was problematic for me as I already have some issues with lymphedema in my right arm. This too was discovered in the first week (not the lymphedema, but that it was going to be a big problem) and their lymphedema physical therapist came every day to help me deal with it. 

One thing I think pretty much everyone gets (and it gets worse each week of therapy) are skin issues- rash and very red, dry skin all over that is itchy, but painful. They gave me a small tub of heavy duty moisturizer at the start of each week and I'm glad they did. The skin issues also lasted about a week after the last dose (resolving almost in time for the second week of the cycle). 

It is certainly nothing anyone would consider fun, but it is doable and a good care team that you trust is a big help. I am not sorry I did it at all and am very happy with the care I recieved in Buffalo; I would recommend them to anyone who is considering IL-2. 

I had a partial response- all of the tumors (including one in my spine) I had at the time I started IL-2 did shrink and die off, but very shortly after I finished the therapy new tumors began growing, hence moving to Ipi, which failed miserably, then on to BRAF/MEK combo, which only lasted a few months, so on to PD-1 which is where I am now and doing well. 

Best of luck to you and if you decide to go with IL-2, just remember: it's only a week at a time- you can get through it. You'll feel like garbage, but you'll get through it. One nice thing abou it is that the side effects dissipate within just a few short days after the doses stop so you don't continue to feel horrible for very long.

-Eva

Hi, it's been quite a while since I've posted here myself (over a month, I think) and at the moment I am on PD-1 and it does seem to be working, but I did burn through Interferon, IL-2, Ipi (with WBR), and BRAF/MEK combo (along with 2 rounds of gamma knife plus a craniotomy) before I got here). 

I did IL-2 at Roswell Park Cancer Institute in Buffalo, NY under the care of Dr. Khushalani starting in December 2012 and completed 2 1/2 cycles (total 5 weeks). The 1/2 cycle was actually the first cycle as I developed severe colitis and was held in the hospital on fluid therapy for several extra days until that was resolved enough to make the trip home. The second week was cancelled and they weren't sure they wanted to let me come back, but I insisted (though I had to have a colonoscopy before they let me). After that they were very careful with my dosing and everything went as smoothly as it could have. They were also very cautious about health checks and making sure I was healthy enough to withstand the therapy in the first place. 

It is rough, but, like Interferon, it's a bit different for everyone. It was a bit different each week for me, but I think most people have similar side effects during each week. My main side effects were nausea/vomiting, fatigue, and low blood pressure (I normally have a low blood pressure so this made it even lower). There were a few doses that were skipped due to a slight rise in troponin (an indicator of cardiac stress), and I had a few instances of fever/severe chills, but it was not a predictable/regular side effect for me. I could not eat much of anything for most of the week I was there and every time I had significant colitis, though after the first week we (myself and my care team) were very careful and it was managed much better. I also gained roughly 15-20 pounds in fluid retention, which was all gone within 3-4 days of the last dose of the week. This fluid retention however was problematic for me as I already have some issues with lymphedema in my right arm. This too was discovered in the first week (not the lymphedema, but that it was going to be a big problem) and their lymphedema physical therapist came every day to help me deal with it. 

One thing I think pretty much everyone gets (and it gets worse each week of therapy) are skin issues- rash and very red, dry skin all over that is itchy, but painful. They gave me a small tub of heavy duty moisturizer at the start of each week and I'm glad they did. The skin issues also lasted about a week after the last dose (resolving almost in time for the second week of the cycle). 

It is certainly nothing anyone would consider fun, but it is doable and a good care team that you trust is a big help. I am not sorry I did it at all and am very happy with the care I recieved in Buffalo; I would recommend them to anyone who is considering IL-2. 

I had a partial response- all of the tumors (including one in my spine) I had at the time I started IL-2 did shrink and die off, but very shortly after I finished the therapy new tumors began growing, hence moving to Ipi, which failed miserably, then on to BRAF/MEK combo, which only lasted a few months, so on to PD-1 which is where I am now and doing well. 

Best of luck to you and if you decide to go with IL-2, just remember: it's only a week at a time- you can get through it. You'll feel like garbage, but you'll get through it. One nice thing abou it is that the side effects dissipate within just a few short days after the doses stop so you don't continue to feel horrible for very long.

-Eva

Hi, it's been quite a while since I've posted here myself (over a month, I think) and at the moment I am on PD-1 and it does seem to be working, but I did burn through Interferon, IL-2, Ipi (with WBR), and BRAF/MEK combo (along with 2 rounds of gamma knife plus a craniotomy) before I got here). 

I did IL-2 at Roswell Park Cancer Institute in Buffalo, NY under the care of Dr. Khushalani starting in December 2012 and completed 2 1/2 cycles (total 5 weeks). The 1/2 cycle was actually the first cycle as I developed severe colitis and was held in the hospital on fluid therapy for several extra days until that was resolved enough to make the trip home. The second week was cancelled and they weren't sure they wanted to let me come back, but I insisted (though I had to have a colonoscopy before they let me). After that they were very careful with my dosing and everything went as smoothly as it could have. They were also very cautious about health checks and making sure I was healthy enough to withstand the therapy in the first place. 

It is rough, but, like Interferon, it's a bit different for everyone. It was a bit different each week for me, but I think most people have similar side effects during each week. My main side effects were nausea/vomiting, fatigue, and low blood pressure (I normally have a low blood pressure so this made it even lower). There were a few doses that were skipped due to a slight rise in troponin (an indicator of cardiac stress), and I had a few instances of fever/severe chills, but it was not a predictable/regular side effect for me. I could not eat much of anything for most of the week I was there and every time I had significant colitis, though after the first week we (myself and my care team) were very careful and it was managed much better. I also gained roughly 15-20 pounds in fluid retention, which was all gone within 3-4 days of the last dose of the week. This fluid retention however was problematic for me as I already have some issues with lymphedema in my right arm. This too was discovered in the first week (not the lymphedema, but that it was going to be a big problem) and their lymphedema physical therapist came every day to help me deal with it. 

One thing I think pretty much everyone gets (and it gets worse each week of therapy) are skin issues- rash and very red, dry skin all over that is itchy, but painful. They gave me a small tub of heavy duty moisturizer at the start of each week and I'm glad they did. The skin issues also lasted about a week after the last dose (resolving almost in time for the second week of the cycle). 

It is certainly nothing anyone would consider fun, but it is doable and a good care team that you trust is a big help. I am not sorry I did it at all and am very happy with the care I recieved in Buffalo; I would recommend them to anyone who is considering IL-2. 

I had a partial response- all of the tumors (including one in my spine) I had at the time I started IL-2 did shrink and die off, but very shortly after I finished the therapy new tumors began growing, hence moving to Ipi, which failed miserably, then on to BRAF/MEK combo, which only lasted a few months, so on to PD-1 which is where I am now and doing well. 

Best of luck to you and if you decide to go with IL-2, just remember: it's only a week at a time- you can get through it. You'll feel like garbage, but you'll get through it. One nice thing abou it is that the side effects dissipate within just a few short days after the doses stop so you don't continue to feel horrible for very long.

-Eva