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Fast relapse after IL2?

Forums General Melanoma Community Fast relapse after IL2?

  • Post
    ecc26
    Participant

      Hello everyone,

      Hello everyone,

      I'm 31 years old and was first diagnosed with melanoma from a mole on my upper back in Jan 2011. At the time I was a stage 3 with only 1 lymph node testing positive for any melanoma (after complete lymph node resection of the right axillary (armpit) area). I completed a full year of interferon and just prior to the end of that therapy found a mass in the scar tissue from the lymph node surgery. That was removed (along with any other tissue that might have lymph nodes in it that they could find) in July of 2012. The mass was melanoma and they couldn't tell if it had been a lymph node or not by the time they took it out. In November 2012 I found (and biopsied) a very small, irritated mass on my left lower abdome that turned out to be melanoma and that put me into stage 4.

      A rush of imaging and other testing got me ready to start IL2 in December 2013, which my team of local oncologists, specialists at Roswell Park in Buffalo, NY and myself decided was the best first option. My scans showed only 3 mets, all subQ, with 2 tiny (questionable) lung mets, but by the time I finished my first week of IL2 I had found at least 4 more subQ's. I had severe side effects from the IL2 and they cancelled the second week, opting instead to rescan in one month to determine if there had been any benefit. After some arguing on my part about the scans (there had been some apparent progresstion since the previous scan, but I had found tumors prior to the start of IL2 that had not been visible on the previous scan so I argued for another try with the IL2) I checked back in for a second round. I tolerated round 2 much better than round 1 and was able to complete both weeks. 8 weeks later (march 2013) the scans showed that with the exception of 2 tumors (both subQ) ALL of my other tumors had either shrunk or dissapeared. My husband and I were thrilled and happy to check in for round 3 thinking that we had gotten this thing under control.

      By the end of the second week of round 3 I could feel that the last 2 tumors that hadn't shrunk on the scans were shrinking and I was on coud 9. Less than a week after I got home from the hospital after round 3 though I had a very sore area over my left pectoral muscle that made me worry. 2 days later I had another sore spot on my lower abdomen. I made an appointment and long story short I now have over a dozen new subQ tumors- several of which have appeared with very large bruising. More than half of them are concentrated in my left breast. I have several questions in my search for information:

      1) Has anyone else had an apperant good response to IL2 then had a relapse (and if so, does anyone know of anyone that relapsed so fast)?

      2) How common is it to have pain/bruising with the appearance of subQ mets? I've had several subQ's before, but never the inflamation/bruising. Does this mean it's worse this time?

      3) I've been told that I have to have failed Ipi before I can begin a clinical trial, but I'm really worried that with the speed tumors are popping up I won't survive the 6 months it takes to determine if I've failed- any thoughts from anyone that has tried Ipi?

      4) I think it's odd that so many are concentrated in my breast- has anyone else experienced this "clustering" of tumors? Also, of all the tumors, there are only 2 on the right side of my body- all others are on the left- again has anyone else experienced this sort of "one sided disease"? I had also noticed during the IL2 that the tumors on the left side of my body (the subQ's that I could feel) seemed to respond slower/less than those on the right side.

       

      I had a CT late last week and I get the resluts to day- I'm more nervous than I think I've been for any of my appointments ever. 

       

      UPDATE MAY 28

      Thank you all for your replies so far. Many of you expressed a need to be informed and active in the decision making process and I couldn't agree more. It's your body and your future and you need to have a say. Rest asured, I'm no push over when it comes to medical anything and I obtained my veterinary degree (which many people, physicians included, don't realize is nearly idenitcal to a human medical degree and certainly just as expensive) just 6 months before my diagnosis and since then have been reading all the same information as any doctor I've been speaking to. For the most part they enjoy my medical expertise as it allows them to discuss factors and options in greater detail than they often are with other patients, but it's taken some getting used to for them with regards to me insisting on seeing all of my imaging for myself (not just relying on reports, etc and I'm entirely unsatisified with human pathology reports- there's almost no usable information in them in comparison to what we get for veterinary path reports) and there have been times when I've argued with their opinions. I'm a regular reader of the research and am very familiar with how trials work, etc. I'm very comfortable with the science and frankly hadn't posted anywhere before becuase my brain is much better with studies and statistics, but I was running into trouble trying to track down statitics to answer some of my questions about what was happening to me now. 

      With regard to the BRAF mutation, at some point late in 2012 (right around the time I started the IL2) I was told that I had been tested for the BRAF and was positive for the mutation (meaning I am eligilble for the BRAF inhibitors), but there seems to be some trouble tracking that result down, making me wonder if I really was tested or if someone mis-spoke when they told me I was positive. I generally insist on getting copies of all my test results (it helps me process to see them for myself and it gives me a nice portfolio to take with me to specialists, etc) but dropped the ball on that one- should have gotten a copy at the time. 

      My appointment today was as good as it was likely to get, I suppose. The CT showed that so far the only new tumors are subQ, although I still need to get a brain MRI to rule in/out any cranial mets. I still have the 2 small lung mets that were present since around the time I started IL2 but they haven't grown and the tumor in the body of T10 that was causing me so much trouble in February has shrunk even more than it had in my scan one month ago. In addition, with the exception of 1 tumor (which is now half the size it was) all of the subQ mets from before/during the IL2 are gone. So It appears that the IL2 did do some good, just not enough/not as much as I and my doctors thought it was. Given these results and the realization that the anti-PD1 trial being opened by the specialist I had been seeing was randomized with chemo in addition to requiring trying Ipi first we (myself and my local oncologist) have decided to schedule an appointment at Dana-Farber in Boston, MA to discuss possibly joining one of their trials, etc. I have to wait another 1-2 weeks anyway before starting either a trial or Ipi since I'm so close to my last round of IL2 so it makes sense to maybe take a look at some other area cancer centers and see what's available for me. I'm also curious about the T-cell therapy trials, although I haven't had time to research the trial results, etc much yet.

      Thanks again everyone for posting and for the info about your experiences and trials- it's really not that easy to research what trials are available or rather what the mechanism/action of the drug being tested is.No one wants to divulge their reserarch before it's patented, but it can be hard to sift out which are the PD1 and which are other less promising therapies.

    Viewing 14 reply threads
    • Replies
        Phil S
        Participant
          My husband did a clinical trial, and has NEVER done IPI, I would investigate this further, that doesn’t sound correct. Plus, in your shoes I would look into the AntiPD1 and Ipi combo trials, since your are Ipi naive. You have to advocate for yourself, and unfortunately educate yourself on choices, I know it’s hard, hopefully you have supportive family to help you navigate the medical system. Keep us posted, we are cheering you on. Keep fighting!! Valerie (Phil’s wife)
          Phil S
          Participant
            My husband did a clinical trial, and has NEVER done IPI, I would investigate this further, that doesn’t sound correct. Plus, in your shoes I would look into the AntiPD1 and Ipi combo trials, since your are Ipi naive. You have to advocate for yourself, and unfortunately educate yourself on choices, I know it’s hard, hopefully you have supportive family to help you navigate the medical system. Keep us posted, we are cheering you on. Keep fighting!! Valerie (Phil’s wife)
              ecc26
              Participant

                You are correct, I was trying to keep my story on the shorter side and what I meant (and should have written) was that the studies available in Buffalo, NY (the cancer treatment center closest to me that I have been working with) require Ipi be tried prior to admission in the trials. On further investigation I don't think I'll be looking at those trials anyway as they are randomized with one of 3 chemo agents. I know someone has to participate in randomized tirals, but I'm really not comfortable at this point taking the chance of getting the chemo instead of the anti PD1. The Ipi combo trials sound interesting, I was unaware of these, although in addition to the anti PD1 the T cell therapy caught my eye.

                ecc26
                Participant

                  You are correct, I was trying to keep my story on the shorter side and what I meant (and should have written) was that the studies available in Buffalo, NY (the cancer treatment center closest to me that I have been working with) require Ipi be tried prior to admission in the trials. On further investigation I don't think I'll be looking at those trials anyway as they are randomized with one of 3 chemo agents. I know someone has to participate in randomized tirals, but I'm really not comfortable at this point taking the chance of getting the chemo instead of the anti PD1. The Ipi combo trials sound interesting, I was unaware of these, although in addition to the anti PD1 the T cell therapy caught my eye.

                  ecc26
                  Participant

                    You are correct, I was trying to keep my story on the shorter side and what I meant (and should have written) was that the studies available in Buffalo, NY (the cancer treatment center closest to me that I have been working with) require Ipi be tried prior to admission in the trials. On further investigation I don't think I'll be looking at those trials anyway as they are randomized with one of 3 chemo agents. I know someone has to participate in randomized tirals, but I'm really not comfortable at this point taking the chance of getting the chemo instead of the anti PD1. The Ipi combo trials sound interesting, I was unaware of these, although in addition to the anti PD1 the T cell therapy caught my eye.

                  Phil S
                  Participant
                    My husband did a clinical trial, and has NEVER done IPI, I would investigate this further, that doesn’t sound correct. Plus, in your shoes I would look into the AntiPD1 and Ipi combo trials, since your are Ipi naive. You have to advocate for yourself, and unfortunately educate yourself on choices, I know it’s hard, hopefully you have supportive family to help you navigate the medical system. Keep us posted, we are cheering you on. Keep fighting!! Valerie (Phil’s wife)
                    NYKaren
                    Participant

                      Hi, I did IL2 over 2.5 courses (5 weeks in total).  In the beginning we thought I was responding, but after all was said and done, i began to progress.  That's not to say it didn't do me any good, but if anything, I was only a partial responder.

                      I would strongly suggest you look into the Ipi and PD1 combo trial.   And I agree, you do not have to have failed Ipi to get into many trials, and you certainly don't have to wait 6 months!   The major PD1 players are moving fast…the MERCK drug has been designated as a "fast-track" drug by the FDA (nobody quite knows what that means, although it seems to be making the trials easier to get into.(  I know a lot of the obsticles are out of my way that were there in the past. 

                      Although I'm "only" Stage IIIC unresectable, my disease has been mostly on the right side of my body, scalp, face, ear, neck, although I am starting to get scalp mets on my left side. 

                      Were you tested for the BRAF  mutation?  That is crucial.

                      wishing you the best and please keep us posted,

                      Karen

                      PS, although I am at Sloan Kettering, one of the best instutions in the world and I trust my doctors implicitly, I always do my homework and try to be as up-to-date as possible on everything that is going on.

                      Read all you can here…also look at Melanomainternational.org.  Catherine Poole over there is excellent with advice about clinical trials.

                      NYKaren
                      Participant

                        Hi, I did IL2 over 2.5 courses (5 weeks in total).  In the beginning we thought I was responding, but after all was said and done, i began to progress.  That's not to say it didn't do me any good, but if anything, I was only a partial responder.

                        I would strongly suggest you look into the Ipi and PD1 combo trial.   And I agree, you do not have to have failed Ipi to get into many trials, and you certainly don't have to wait 6 months!   The major PD1 players are moving fast…the MERCK drug has been designated as a "fast-track" drug by the FDA (nobody quite knows what that means, although it seems to be making the trials easier to get into.(  I know a lot of the obsticles are out of my way that were there in the past. 

                        Although I'm "only" Stage IIIC unresectable, my disease has been mostly on the right side of my body, scalp, face, ear, neck, although I am starting to get scalp mets on my left side. 

                        Were you tested for the BRAF  mutation?  That is crucial.

                        wishing you the best and please keep us posted,

                        Karen

                        PS, although I am at Sloan Kettering, one of the best instutions in the world and I trust my doctors implicitly, I always do my homework and try to be as up-to-date as possible on everything that is going on.

                        Read all you can here…also look at Melanomainternational.org.  Catherine Poole over there is excellent with advice about clinical trials.

                          ecc26
                          Participant

                            "Fast tracking" through the FDA just means that given the promising results from earlier studies they get sort of waived through some of the red tape and may get to skip some steps so long as they can prove a relatively good safety margin. For example, due to the excellent long term results demonstrated for responders to IL2 in the early tirals (even though only a small percentage actually respond) the FDA "fast tracked" the drug and it was approved for general use after only phase II trials whereas other drugs have to go through phase III tials (or more) and have a large burden of proof to accomplish showing safety and efficacy. It's a very long and arduous process that the majority of drugs fail and those that do succeed often take 10+ years. It's part of why the cost of these drugs is so high- it takes decades of research and development before they get something that can be used. That the anti PD1s have been fast tracked is a reflection of the promising results from the early trials, which is good and why so many new trials are opening and so many people are looking to join them. 

                            Thank you for your post though and good luck to you. My original tumor was on the right side of my back and almost all of the original mets were also on the right, now they're all on the left and I just found it odd that they were so concentrated in certain areas instead of being more randomly distributed and wondered if anyone else had had a similar experience.

                            ecc26
                            Participant

                              "Fast tracking" through the FDA just means that given the promising results from earlier studies they get sort of waived through some of the red tape and may get to skip some steps so long as they can prove a relatively good safety margin. For example, due to the excellent long term results demonstrated for responders to IL2 in the early tirals (even though only a small percentage actually respond) the FDA "fast tracked" the drug and it was approved for general use after only phase II trials whereas other drugs have to go through phase III tials (or more) and have a large burden of proof to accomplish showing safety and efficacy. It's a very long and arduous process that the majority of drugs fail and those that do succeed often take 10+ years. It's part of why the cost of these drugs is so high- it takes decades of research and development before they get something that can be used. That the anti PD1s have been fast tracked is a reflection of the promising results from the early trials, which is good and why so many new trials are opening and so many people are looking to join them. 

                              Thank you for your post though and good luck to you. My original tumor was on the right side of my back and almost all of the original mets were also on the right, now they're all on the left and I just found it odd that they were so concentrated in certain areas instead of being more randomly distributed and wondered if anyone else had had a similar experience.

                              ecc26
                              Participant

                                "Fast tracking" through the FDA just means that given the promising results from earlier studies they get sort of waived through some of the red tape and may get to skip some steps so long as they can prove a relatively good safety margin. For example, due to the excellent long term results demonstrated for responders to IL2 in the early tirals (even though only a small percentage actually respond) the FDA "fast tracked" the drug and it was approved for general use after only phase II trials whereas other drugs have to go through phase III tials (or more) and have a large burden of proof to accomplish showing safety and efficacy. It's a very long and arduous process that the majority of drugs fail and those that do succeed often take 10+ years. It's part of why the cost of these drugs is so high- it takes decades of research and development before they get something that can be used. That the anti PD1s have been fast tracked is a reflection of the promising results from the early trials, which is good and why so many new trials are opening and so many people are looking to join them. 

                                Thank you for your post though and good luck to you. My original tumor was on the right side of my back and almost all of the original mets were also on the right, now they're all on the left and I just found it odd that they were so concentrated in certain areas instead of being more randomly distributed and wondered if anyone else had had a similar experience.

                              NYKaren
                              Participant

                                Hi, I did IL2 over 2.5 courses (5 weeks in total).  In the beginning we thought I was responding, but after all was said and done, i began to progress.  That's not to say it didn't do me any good, but if anything, I was only a partial responder.

                                I would strongly suggest you look into the Ipi and PD1 combo trial.   And I agree, you do not have to have failed Ipi to get into many trials, and you certainly don't have to wait 6 months!   The major PD1 players are moving fast…the MERCK drug has been designated as a "fast-track" drug by the FDA (nobody quite knows what that means, although it seems to be making the trials easier to get into.(  I know a lot of the obsticles are out of my way that were there in the past. 

                                Although I'm "only" Stage IIIC unresectable, my disease has been mostly on the right side of my body, scalp, face, ear, neck, although I am starting to get scalp mets on my left side. 

                                Were you tested for the BRAF  mutation?  That is crucial.

                                wishing you the best and please keep us posted,

                                Karen

                                PS, although I am at Sloan Kettering, one of the best instutions in the world and I trust my doctors implicitly, I always do my homework and try to be as up-to-date as possible on everything that is going on.

                                Read all you can here…also look at Melanomainternational.org.  Catherine Poole over there is excellent with advice about clinical trials.

                                Tamils
                                Participant

                                  Regarding your question #3:  There is a Merck anti-PD1 trial that has 1000+ slots just opening now (http://clinicaltrials.gov/ct2/show/NCT01295827?term=mk-3475&rank=4).  My father just signed the consent forms, and he was accepted having taken only one dose of ipi and having scans a few weeks after the dose showing progression compared to earlier scans.  There was a six-week waiting period required after his ipi dose before the first anti-PD1 dose could be given; however, you may be able to qualify sooner than you may think.  I should also add that he took the ipi at the study doctor's suggestion, primarily in order to qualify for the trial.  There was no expectation that the ipi would have reduced any tumors within the few weeks between the dose and the scan, but even one dose might do some good down the line, or in priming his system for the anti-PD1 to work.        

                                  Tamils
                                  Participant

                                    Regarding your question #3:  There is a Merck anti-PD1 trial that has 1000+ slots just opening now (http://clinicaltrials.gov/ct2/show/NCT01295827?term=mk-3475&rank=4).  My father just signed the consent forms, and he was accepted having taken only one dose of ipi and having scans a few weeks after the dose showing progression compared to earlier scans.  There was a six-week waiting period required after his ipi dose before the first anti-PD1 dose could be given; however, you may be able to qualify sooner than you may think.  I should also add that he took the ipi at the study doctor's suggestion, primarily in order to qualify for the trial.  There was no expectation that the ipi would have reduced any tumors within the few weeks between the dose and the scan, but even one dose might do some good down the line, or in priming his system for the anti-PD1 to work.        

                                    Tamils
                                    Participant

                                      Regarding your question #3:  There is a Merck anti-PD1 trial that has 1000+ slots just opening now (http://clinicaltrials.gov/ct2/show/NCT01295827?term=mk-3475&rank=4).  My father just signed the consent forms, and he was accepted having taken only one dose of ipi and having scans a few weeks after the dose showing progression compared to earlier scans.  There was a six-week waiting period required after his ipi dose before the first anti-PD1 dose could be given; however, you may be able to qualify sooner than you may think.  I should also add that he took the ipi at the study doctor's suggestion, primarily in order to qualify for the trial.  There was no expectation that the ipi would have reduced any tumors within the few weeks between the dose and the scan, but even one dose might do some good down the line, or in priming his system for the anti-PD1 to work.        

                                      SteveH230
                                      Participant

                                        Sorry to hear that IL-2 did not work completely for you.  I have learned a lot from this forum and though I've never posted, your post prompted me to finally chime in.  My wife Heather is 32 & in otherwise great health, so was deemed a good candidate for IL-2 as a first-line treatment for stage IV melanoma starting in October 2012.  

                                        At the time, she had known mets in her liver, spleen, bone, sub-cutaneous, and soft tissue.  After the first two rounds (one course) the scans showed shrinkage in all spots, so we too were excited to go back for round 3.  Sometime during that 3rd round, we noticed a painful lump growing in the subcutaneous tissue of her upper arm.  Her doctor didn't stop the treatment immediately, so she completed round 3 of IL-2 (11 doses for a grand total of 30).  He ordered a biopsy shortly thereafter, which came back positive for melanoma.   We didn't go back for week 4 of IL-2 and instead started IPI in January 2013.  The pre-IPI scans showed that the internal tumors had been shrunk and/or stabilized by IL-2, but the new appearance on her arm was sufficient to cause a change of plans.  

                                        During IPI (Jan-March 2013), many small sub-Q lumps appeared in her arms, thighs, and trunk.  She didn't have any bruising associated with these, and most did not hurt to the touch either, so unfortunately I don't have any first-hand experience with the bruising to tell you about.  Her April scans showed progression (by RECIST criteria), and the MRI revealed two tiny (less than 1 and 2 mm) new mets on her meninges that at needed stereotactic radiosurgery followed by an 8-week wait before she can be eligible for any of the anti PD-1 trials.  We are now in the post-SRS waiting period before a new MRI can be used to confirm stability.  In the interim, she has done one dose of Carbo Taxol chemo which along with IPI has seemed to stabilize things.

                                        I don't tell you all this to scare or bore you, but to just reinforce the point that IPI monotherapy is known to help a pretty small minority of patients.  The response rates vary, but the highest I've seen is 20%.  Significant progression can still occur for the majority of patients.  That said, I think Heather may be getting delayed (if not immediately shown by scans) benefit from IPI, as her LDH levels have been decreasing steadily, pain has gone away, etc.  Either way, she doesn't really have any symptoms and is "doing well," despite failing the two standard immunotherapy treatments and approaching the 1-yr anniversary of her stage IV diagnosis.  All this to say that IL-2 and IPI seem to have helped her despite "failing" them by the traditional RECIST criteria.  In fact, we went to see her doctor today and he was grinning from ear to ear at her lovely appearance, solid bloodwork numbers, knowing she's staying active and feeling good, etc.  He is more confident that ever that the emerging drugs/treatments will help her continue getting better, and looks forward to hearing all the updated data at ASCO next week.  

                                        Though the data is less mature, anti PD-1 seems to help a significantly higher % of patients than IPI by itself.  Further, there are new trials available that are combining IPI and anti PD-1 sequentially/concurrently that are showing  better response rates than either of these drugs alone.  

                                        Although some of the trials have "IPI failure" as a requirement, this is not the case for all, especially the 'combo' IPI/anti PD-1 trials.  It might just be that these trials are not available at your current facility. Hope that wasn't information overload, but we had a very similar experience with IL-2 and wanted to weigh in.

                                        Sorry if someone else already brought this up, but has your medical team checked for the BRAF mutation yet?  If not, that would probably be the next thing to look at before anti PD-1.  Vemurafenib would be available to you if you have the mutation, which is known to work well and fast.  If I'm not mistaken, the anti PD-1 trials ARE requiring BRAF-positive patients to have done this treatment first.  

                                        Let me know if I can help with any other questions.  Praying for good results on your scans-

                                        Steve

                                        SteveH230
                                        Participant

                                          Sorry to hear that IL-2 did not work completely for you.  I have learned a lot from this forum and though I've never posted, your post prompted me to finally chime in.  My wife Heather is 32 & in otherwise great health, so was deemed a good candidate for IL-2 as a first-line treatment for stage IV melanoma starting in October 2012.  

                                          At the time, she had known mets in her liver, spleen, bone, sub-cutaneous, and soft tissue.  After the first two rounds (one course) the scans showed shrinkage in all spots, so we too were excited to go back for round 3.  Sometime during that 3rd round, we noticed a painful lump growing in the subcutaneous tissue of her upper arm.  Her doctor didn't stop the treatment immediately, so she completed round 3 of IL-2 (11 doses for a grand total of 30).  He ordered a biopsy shortly thereafter, which came back positive for melanoma.   We didn't go back for week 4 of IL-2 and instead started IPI in January 2013.  The pre-IPI scans showed that the internal tumors had been shrunk and/or stabilized by IL-2, but the new appearance on her arm was sufficient to cause a change of plans.  

                                          During IPI (Jan-March 2013), many small sub-Q lumps appeared in her arms, thighs, and trunk.  She didn't have any bruising associated with these, and most did not hurt to the touch either, so unfortunately I don't have any first-hand experience with the bruising to tell you about.  Her April scans showed progression (by RECIST criteria), and the MRI revealed two tiny (less than 1 and 2 mm) new mets on her meninges that at needed stereotactic radiosurgery followed by an 8-week wait before she can be eligible for any of the anti PD-1 trials.  We are now in the post-SRS waiting period before a new MRI can be used to confirm stability.  In the interim, she has done one dose of Carbo Taxol chemo which along with IPI has seemed to stabilize things.

                                          I don't tell you all this to scare or bore you, but to just reinforce the point that IPI monotherapy is known to help a pretty small minority of patients.  The response rates vary, but the highest I've seen is 20%.  Significant progression can still occur for the majority of patients.  That said, I think Heather may be getting delayed (if not immediately shown by scans) benefit from IPI, as her LDH levels have been decreasing steadily, pain has gone away, etc.  Either way, she doesn't really have any symptoms and is "doing well," despite failing the two standard immunotherapy treatments and approaching the 1-yr anniversary of her stage IV diagnosis.  All this to say that IL-2 and IPI seem to have helped her despite "failing" them by the traditional RECIST criteria.  In fact, we went to see her doctor today and he was grinning from ear to ear at her lovely appearance, solid bloodwork numbers, knowing she's staying active and feeling good, etc.  He is more confident that ever that the emerging drugs/treatments will help her continue getting better, and looks forward to hearing all the updated data at ASCO next week.  

                                          Though the data is less mature, anti PD-1 seems to help a significantly higher % of patients than IPI by itself.  Further, there are new trials available that are combining IPI and anti PD-1 sequentially/concurrently that are showing  better response rates than either of these drugs alone.  

                                          Although some of the trials have "IPI failure" as a requirement, this is not the case for all, especially the 'combo' IPI/anti PD-1 trials.  It might just be that these trials are not available at your current facility. Hope that wasn't information overload, but we had a very similar experience with IL-2 and wanted to weigh in.

                                          Sorry if someone else already brought this up, but has your medical team checked for the BRAF mutation yet?  If not, that would probably be the next thing to look at before anti PD-1.  Vemurafenib would be available to you if you have the mutation, which is known to work well and fast.  If I'm not mistaken, the anti PD-1 trials ARE requiring BRAF-positive patients to have done this treatment first.  

                                          Let me know if I can help with any other questions.  Praying for good results on your scans-

                                          Steve

                                            buffcody
                                            Participant

                                              What a wonderfully informative and helpful post.  I hope you will continue  to "chime" in often to assist us.

                                              buffcody
                                              Participant

                                                What a wonderfully informative and helpful post.  I hope you will continue  to "chime" in often to assist us.

                                                SteveH230
                                                Participant
                                                  Glad it was helpful and I certainly will!
                                                  SteveH230
                                                  Participant
                                                    Glad it was helpful and I certainly will!
                                                    SteveH230
                                                    Participant
                                                      Glad it was helpful and I certainly will!
                                                      buffcody
                                                      Participant

                                                        What a wonderfully informative and helpful post.  I hope you will continue  to "chime" in often to assist us.

                                                        ecc26
                                                        Participant

                                                          Thank you for your post- I really hope the anti-PD1 trials are successful for you and your wife. Her story certainly has several parallels to mine and that was one thing I was questioning: how typical is it to appear to have a good response to IL2, then have new tumors so quickly and to have those new tumors "behave" differently from the previous tumors. Most of the research simply states the average disease free intervals or progression free intervals of responders and my case didn't really seem to fit with that. Similar to the bruising, etc which I had not experienced before with my other mets. Interesting that your wife also had a painful met around the time of the IL2. I had refrained from posting on message boards as well feeling like I had a good support system (which I do) and knowing that my brain functions much better with statistics, percentages, and studies, etc than with individual stories but had run into some questions I wasn't finding good info for. I'm glad I did- I'm getting some good info about trials and starting to feel a little more confidant again. Each time things start to progress again I get frustrated and angry and a little more scared. One of the worst parts about the whole thing is knowing how worried my husband is, even though he never shows it. I hate that he has to go through this and all I want to do is give him a little more peace of mind.

                                                          Thank you again for your post and good luck to you both

                                                          ecc26
                                                          Participant

                                                            Thank you for your post- I really hope the anti-PD1 trials are successful for you and your wife. Her story certainly has several parallels to mine and that was one thing I was questioning: how typical is it to appear to have a good response to IL2, then have new tumors so quickly and to have those new tumors "behave" differently from the previous tumors. Most of the research simply states the average disease free intervals or progression free intervals of responders and my case didn't really seem to fit with that. Similar to the bruising, etc which I had not experienced before with my other mets. Interesting that your wife also had a painful met around the time of the IL2. I had refrained from posting on message boards as well feeling like I had a good support system (which I do) and knowing that my brain functions much better with statistics, percentages, and studies, etc than with individual stories but had run into some questions I wasn't finding good info for. I'm glad I did- I'm getting some good info about trials and starting to feel a little more confidant again. Each time things start to progress again I get frustrated and angry and a little more scared. One of the worst parts about the whole thing is knowing how worried my husband is, even though he never shows it. I hate that he has to go through this and all I want to do is give him a little more peace of mind.

                                                            Thank you again for your post and good luck to you both

                                                            ecc26
                                                            Participant

                                                              Thank you for your post- I really hope the anti-PD1 trials are successful for you and your wife. Her story certainly has several parallels to mine and that was one thing I was questioning: how typical is it to appear to have a good response to IL2, then have new tumors so quickly and to have those new tumors "behave" differently from the previous tumors. Most of the research simply states the average disease free intervals or progression free intervals of responders and my case didn't really seem to fit with that. Similar to the bruising, etc which I had not experienced before with my other mets. Interesting that your wife also had a painful met around the time of the IL2. I had refrained from posting on message boards as well feeling like I had a good support system (which I do) and knowing that my brain functions much better with statistics, percentages, and studies, etc than with individual stories but had run into some questions I wasn't finding good info for. I'm glad I did- I'm getting some good info about trials and starting to feel a little more confidant again. Each time things start to progress again I get frustrated and angry and a little more scared. One of the worst parts about the whole thing is knowing how worried my husband is, even though he never shows it. I hate that he has to go through this and all I want to do is give him a little more peace of mind.

                                                              Thank you again for your post and good luck to you both

                                                              SteveH230
                                                              Participant
                                                                Thank you very much for the well wishes! We too were overjoyed at the report after 2 rounds of IL-2 that things were shrinking. At that point, I thought she was already a responder and it was just a question of whether it would be complete or partial… But later realized that to be an official ‘partial responder’ per RECIST criteria, you have to have confirmed evidence of greater than 50% of the tumor volume (on the ones they have measured and are tracking with the scans). Also, if just one new lesion pops up, it automatically puts you in the failure category.

                                                                IPI and anti PD-1 along with other immunotherapies have shown different response patterns, where you can progress initially and then have a response later on, even in the presence of new lesions. This has led to the proposal of a new response criteria method called iRR (i think, immune-based response criteria). Under this method, the total overall tumor volume is evaluated, so you can eventually become a responder even new spots pop up in the beginning. It doesn’t seem to be relevant to IL-2, which is more ‘all or nothing’ in its overall effectiveness, but some of the newer IPI and anti PD-1 trials are using this iRR method to evaluate response rates. There are stories out there of patients who have had some new things pop up early on during treatment, only to later achieve a partial or complete response. It often takes time for the immune system to get revved up, it seems, for some of these new treatments.

                                                                I think you’ll find that ‘internet stats’ are a bit outdated and widely varying, based mostly on older treatments like chemotherapy, surgery, and IL-2. I was really upset when I Googled stage IV melanoma for the first time. We had only been married 2.5 months when this started. But I have learned now that the new drugs are changing the game and there are more promising options than ever before. Even if a treament ‘fails’ by the old criteria, you can still have a small or delayed response which buys more time until the right treatment for you is found and works. ‘Largely stable’ is not a bad thing… though we all want that complete response and want it now! I maintain a high level of hope and I try to focus on the positive and things we can control, especially when talking to my wife about things. Diet, exercise, attitude, and support from family and friends all play a big role for us. Like your husband, I tend to keep the worry and fear to myself, but I am becoming more encouraged and confident every day as news come out on these new options.

                                                                We have one more round of Chemo tomorrow and then we wait until early July to try and enroll in a trial. Hopefully there are still phase 1 trials still open for Merck and/or BMS’s ant PD-1 by then, but if not, Merck’s big phase 2 trial allows for crossover… So if you end up in the chemo arm, you can move over to the study drug when progression occurs.

                                                                All the best,
                                                                Steve

                                                                SteveH230
                                                                Participant
                                                                  Thank you very much for the well wishes! We too were overjoyed at the report after 2 rounds of IL-2 that things were shrinking. At that point, I thought she was already a responder and it was just a question of whether it would be complete or partial… But later realized that to be an official ‘partial responder’ per RECIST criteria, you have to have confirmed evidence of greater than 50% of the tumor volume (on the ones they have measured and are tracking with the scans). Also, if just one new lesion pops up, it automatically puts you in the failure category.

                                                                  IPI and anti PD-1 along with other immunotherapies have shown different response patterns, where you can progress initially and then have a response later on, even in the presence of new lesions. This has led to the proposal of a new response criteria method called iRR (i think, immune-based response criteria). Under this method, the total overall tumor volume is evaluated, so you can eventually become a responder even new spots pop up in the beginning. It doesn’t seem to be relevant to IL-2, which is more ‘all or nothing’ in its overall effectiveness, but some of the newer IPI and anti PD-1 trials are using this iRR method to evaluate response rates. There are stories out there of patients who have had some new things pop up early on during treatment, only to later achieve a partial or complete response. It often takes time for the immune system to get revved up, it seems, for some of these new treatments.

                                                                  I think you’ll find that ‘internet stats’ are a bit outdated and widely varying, based mostly on older treatments like chemotherapy, surgery, and IL-2. I was really upset when I Googled stage IV melanoma for the first time. We had only been married 2.5 months when this started. But I have learned now that the new drugs are changing the game and there are more promising options than ever before. Even if a treament ‘fails’ by the old criteria, you can still have a small or delayed response which buys more time until the right treatment for you is found and works. ‘Largely stable’ is not a bad thing… though we all want that complete response and want it now! I maintain a high level of hope and I try to focus on the positive and things we can control, especially when talking to my wife about things. Diet, exercise, attitude, and support from family and friends all play a big role for us. Like your husband, I tend to keep the worry and fear to myself, but I am becoming more encouraged and confident every day as news come out on these new options.

                                                                  We have one more round of Chemo tomorrow and then we wait until early July to try and enroll in a trial. Hopefully there are still phase 1 trials still open for Merck and/or BMS’s ant PD-1 by then, but if not, Merck’s big phase 2 trial allows for crossover… So if you end up in the chemo arm, you can move over to the study drug when progression occurs.

                                                                  All the best,
                                                                  Steve

                                                                  SteveH230
                                                                  Participant
                                                                    Thank you very much for the well wishes! We too were overjoyed at the report after 2 rounds of IL-2 that things were shrinking. At that point, I thought she was already a responder and it was just a question of whether it would be complete or partial… But later realized that to be an official ‘partial responder’ per RECIST criteria, you have to have confirmed evidence of greater than 50% of the tumor volume (on the ones they have measured and are tracking with the scans). Also, if just one new lesion pops up, it automatically puts you in the failure category.

                                                                    IPI and anti PD-1 along with other immunotherapies have shown different response patterns, where you can progress initially and then have a response later on, even in the presence of new lesions. This has led to the proposal of a new response criteria method called iRR (i think, immune-based response criteria). Under this method, the total overall tumor volume is evaluated, so you can eventually become a responder even new spots pop up in the beginning. It doesn’t seem to be relevant to IL-2, which is more ‘all or nothing’ in its overall effectiveness, but some of the newer IPI and anti PD-1 trials are using this iRR method to evaluate response rates. There are stories out there of patients who have had some new things pop up early on during treatment, only to later achieve a partial or complete response. It often takes time for the immune system to get revved up, it seems, for some of these new treatments.

                                                                    I think you’ll find that ‘internet stats’ are a bit outdated and widely varying, based mostly on older treatments like chemotherapy, surgery, and IL-2. I was really upset when I Googled stage IV melanoma for the first time. We had only been married 2.5 months when this started. But I have learned now that the new drugs are changing the game and there are more promising options than ever before. Even if a treament ‘fails’ by the old criteria, you can still have a small or delayed response which buys more time until the right treatment for you is found and works. ‘Largely stable’ is not a bad thing… though we all want that complete response and want it now! I maintain a high level of hope and I try to focus on the positive and things we can control, especially when talking to my wife about things. Diet, exercise, attitude, and support from family and friends all play a big role for us. Like your husband, I tend to keep the worry and fear to myself, but I am becoming more encouraged and confident every day as news come out on these new options.

                                                                    We have one more round of Chemo tomorrow and then we wait until early July to try and enroll in a trial. Hopefully there are still phase 1 trials still open for Merck and/or BMS’s ant PD-1 by then, but if not, Merck’s big phase 2 trial allows for crossover… So if you end up in the chemo arm, you can move over to the study drug when progression occurs.

                                                                    All the best,
                                                                    Steve

                                                                  SteveH230
                                                                  Participant

                                                                    Sorry to hear that IL-2 did not work completely for you.  I have learned a lot from this forum and though I've never posted, your post prompted me to finally chime in.  My wife Heather is 32 & in otherwise great health, so was deemed a good candidate for IL-2 as a first-line treatment for stage IV melanoma starting in October 2012.  

                                                                    At the time, she had known mets in her liver, spleen, bone, sub-cutaneous, and soft tissue.  After the first two rounds (one course) the scans showed shrinkage in all spots, so we too were excited to go back for round 3.  Sometime during that 3rd round, we noticed a painful lump growing in the subcutaneous tissue of her upper arm.  Her doctor didn't stop the treatment immediately, so she completed round 3 of IL-2 (11 doses for a grand total of 30).  He ordered a biopsy shortly thereafter, which came back positive for melanoma.   We didn't go back for week 4 of IL-2 and instead started IPI in January 2013.  The pre-IPI scans showed that the internal tumors had been shrunk and/or stabilized by IL-2, but the new appearance on her arm was sufficient to cause a change of plans.  

                                                                    During IPI (Jan-March 2013), many small sub-Q lumps appeared in her arms, thighs, and trunk.  She didn't have any bruising associated with these, and most did not hurt to the touch either, so unfortunately I don't have any first-hand experience with the bruising to tell you about.  Her April scans showed progression (by RECIST criteria), and the MRI revealed two tiny (less than 1 and 2 mm) new mets on her meninges that at needed stereotactic radiosurgery followed by an 8-week wait before she can be eligible for any of the anti PD-1 trials.  We are now in the post-SRS waiting period before a new MRI can be used to confirm stability.  In the interim, she has done one dose of Carbo Taxol chemo which along with IPI has seemed to stabilize things.

                                                                    I don't tell you all this to scare or bore you, but to just reinforce the point that IPI monotherapy is known to help a pretty small minority of patients.  The response rates vary, but the highest I've seen is 20%.  Significant progression can still occur for the majority of patients.  That said, I think Heather may be getting delayed (if not immediately shown by scans) benefit from IPI, as her LDH levels have been decreasing steadily, pain has gone away, etc.  Either way, she doesn't really have any symptoms and is "doing well," despite failing the two standard immunotherapy treatments and approaching the 1-yr anniversary of her stage IV diagnosis.  All this to say that IL-2 and IPI seem to have helped her despite "failing" them by the traditional RECIST criteria.  In fact, we went to see her doctor today and he was grinning from ear to ear at her lovely appearance, solid bloodwork numbers, knowing she's staying active and feeling good, etc.  He is more confident that ever that the emerging drugs/treatments will help her continue getting better, and looks forward to hearing all the updated data at ASCO next week.  

                                                                    Though the data is less mature, anti PD-1 seems to help a significantly higher % of patients than IPI by itself.  Further, there are new trials available that are combining IPI and anti PD-1 sequentially/concurrently that are showing  better response rates than either of these drugs alone.  

                                                                    Although some of the trials have "IPI failure" as a requirement, this is not the case for all, especially the 'combo' IPI/anti PD-1 trials.  It might just be that these trials are not available at your current facility. Hope that wasn't information overload, but we had a very similar experience with IL-2 and wanted to weigh in.

                                                                    Sorry if someone else already brought this up, but has your medical team checked for the BRAF mutation yet?  If not, that would probably be the next thing to look at before anti PD-1.  Vemurafenib would be available to you if you have the mutation, which is known to work well and fast.  If I'm not mistaken, the anti PD-1 trials ARE requiring BRAF-positive patients to have done this treatment first.  

                                                                    Let me know if I can help with any other questions.  Praying for good results on your scans-

                                                                    Steve

                                                                    BrianP
                                                                    Participant

                                                                      If you are still interested in the TIL clinical trials the webinar on MIF is outstanding.  It sounds like they are looking for customers.

                                                                      http://www.melanomainternational.org/news/ 

                                                                      Good luck.

                                                                      Brian

                                                                        ecc26
                                                                        Participant

                                                                          Thank You!

                                                                          ecc26
                                                                          Participant

                                                                            Thank You!

                                                                            ecc26
                                                                            Participant

                                                                              Thank You!

                                                                            BrianP
                                                                            Participant

                                                                              If you are still interested in the TIL clinical trials the webinar on MIF is outstanding.  It sounds like they are looking for customers.

                                                                              http://www.melanomainternational.org/news/ 

                                                                              Good luck.

                                                                              Brian

                                                                              BrianP
                                                                              Participant

                                                                                If you are still interested in the TIL clinical trials the webinar on MIF is outstanding.  It sounds like they are looking for customers.

                                                                                http://www.melanomainternational.org/news/ 

                                                                                Good luck.

                                                                                Brian

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