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NY times on heart toxicity for combination yervoy/opdivo patients 11/2/16

Forums General Melanoma Community NY times on heart toxicity for combination yervoy/opdivo patients 11/2/16

  • Post
    Jubes
    Participant

      Powerful drugs that enlist the immune system to fight cancer can, in rare cases, cause heart damage, doctors are reporting.

      So far, fewer than 1 percent of patients taking these medicines — called checkpoint inhibitors — have developed heart trouble. But in those who do, the damage can be severe, and the drugs have led to several deaths by provoking the immune system to attack the heart. The risk appears highest when patients take two different checkpoint inhibitors at once.
      “This is a new complication of potentially lifesaving drugs,” said Dr. Javid J. Moslehi, the director of cardio-oncology at Vanderbilt School of Medicine and the senior author of an article published Wednesday in The New England Journal of Medicine. “We’re working to develop treatments for it. Our job is not to say the drugs are bad, but to say, ‘How can we deal with it?’”
      The drugs, a form of immunotherapy, are considered a huge breakthrough in cancer treatment. Although they do not work for everyone, they have resulted in lasting remissions for many, including people who were expected to die from advanced cancer that had resisted every other treatment.
      Checkpoint inhibitors have been approved to treat six types of cancer, and are being used for many other types. The drugs are also being combined with one another for added effectiveness.
      The heart findings should not scare patients away from the drugs, Dr. Moslehi said. He called them “transformative” in cancer treatment and said they offered a “potential for cure.”
      Four checkpoint inhibitors are on the market: ipilimumab (brand name Yervoy), nivolumab (Opdivo), pembrolizumab (Keytruda) and atezolizumab (Tecentriq).
      The side effect has prompted some hospitals to add extra cardiac testing for patients taking more than one checkpoint drug, in the hope of catching problems early enough to prevent permanent heart damage. If the tests find signs of trouble, steroids and other drugs may stop the assault by the immune system.
      ↗️ Cell Wars
      “This is something oncologists should be aware of,” said Dr. Jedd D. Wolchok, chief of melanoma and immunotherapeutics services at Memorial Sloan Kettering Cancer Center in New York, who was not an author of the journal article. “It’s rare, but the fact that people have died from it is a reason for us to try to spare them that toxicity.”
      Dr. Wolchok said the problem had occurred in one patient at Sloan Kettering but had cleared up on its own. He agreed that it was advisable to order extra heart tests for patients taking checkpoint combinations.
      Dr. Benjamin A. Olenchock, a study author from the Division of Cardiovascular Medicine at Brigham and Women’s Hospital in Boston, was not available for an interview but said in a written statement that the heart problem had affected patients at his hospital. “As the number of patients treated with checkpoint inhibitors has markedly increased, rare cases of cardiac toxicity associated with the use of these cancer therapeutics, sometimes resulting in death, have been seen at multiple institutions including our own,” the statement said.
      The first checkpoint inhibitor was approved in 2011. The drugs work by unleashing T-cells, a type of white blood cell, to kill cancer. But sometimes, the T-cells go into hyperdrive and attack healthy tissue. Doctors have known for years that the drugs can have dangerous side effects, including gut, lung and thyroid trouble. But the cardiac problems have taken longer to emerge.
      There have been scattered reports in other, less prominent medical journals of heart problems, some fatal, in small numbers of patients taking checkpoint inhibitors alone or in combination. The new report is the most in-depth analysis, including tests for possible genetic or viral causes (none were found) and an examination of a drug-company database to identify other cases.
      The patients described in Dr. Moslehi’s article — a woman, 65, and a man, 63 — developed heart problems and died a few weeks after just one intravenous treatment with a combination of two checkpoint inhibitors: Opdivo and Yervoy. Both patients had advanced melanoma, a deadly skin cancer, and were enrolled in studies. Neither had a history of heart disease.
      The woman had chest pains, shortness of breath and fatigue, and was admitted to the hospital 12 days after her first dose of the drugs. She had myocarditis — inflammation of the heart — as well as other inflamed muscles and abnormal heart rhythms.
      Hoping to quell the inflammation, doctors gave her steroids, but her heart kept deteriorating.
      The man had similar symptoms, and based on their experience with the woman, the Vanderbilt doctors treated him with even higher doses of steroids, as well as another drug. He survived only a few days longer than the woman did, Dr. Moslehi said.
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      Autopsies found that the patients’ immune systems had attacked their hearts, rejecting them as if they were transplants.
      Using data from Bristol-Myers Squibb on 20,594 patients who took the checkpoint inhibitors it makes, Yervoy and Opdivo, the Vanderbilt team found that doctors had reported 18 cases of myocarditis related to the drugs. Six were fatal. The condition was most common and severe in patients who took the combination, affecting 0.27 percent and accounting for five of the six deaths.
      Dr. Michael B. Atkins, the deputy director of the Georgetown Lombardi Comprehensive Cancer Center in Washington, called the rapid onset of heart problems “alarming.” He said the cases had led experts in cancer and myocarditis to meet in September with Bristol-Myers Squibb executives. The group agreed that extra heart tests should be included for patients taking combined checkpoint drugs in studies. The tests include echocardiograms and blood tests for troponin, a protein released by damaged heart muscle.
      The same tests could be done for patients receiving the combined drugs outside of studies, Dr. Atkins said, but he added, “I am unaware of any formal recommendation.”
      Checkpoint inhibitors “are lifesaving therapies for many patients, at least for melanoma,” Dr. Atkins said. “Around 60 percent of patients have tumor responses to the combination, and the majority of those appear to be long-lasting responses.”
      Before the drugs were available, the median survival time for those with advanced melanoma was six to nine months, and only 10 percent lived two years, he said.
      “We want to do everything we can to make sure these treatments are safe,” he added.
      Dr. Atkins said he thought it would be possible to save patients who developed heart problems by intervening early with powerful drugs to shut down the inflammation. That approach reversed myocarditis in a patient at another hospital in Washington, he said.
      But drugs that stop inflammation work by turning off the immune response, so they may cancel out any benefit from the checkpoint inhibitors. That would leave patients where they started, at the mercy of their cancer, he said.
      So far, there is no way to predict which patients might be vulnerable to heart problems from the checkpoint drugs. For now, Dr. Moslehi said, the best solution is close monitoring for those taking more than one at a time.
      G
    Viewing 14 reply threads
    • Replies
        jennunicorn
        Participant

          Thanks for posting this, I knew there was some kind of heart risk, but forgot to ask my onc to go into detail about what it entails. She had me get an echocardiogram and an ekg before I started the combo and will do them every so often to keep tabs on my heart. Good to know it's a very small chance of this happening, but also kinda scary at the same time.

          jennunicorn
          Participant

            Thanks for posting this, I knew there was some kind of heart risk, but forgot to ask my onc to go into detail about what it entails. She had me get an echocardiogram and an ekg before I started the combo and will do them every so often to keep tabs on my heart. Good to know it's a very small chance of this happening, but also kinda scary at the same time.

            jennunicorn
            Participant

              Thanks for posting this, I knew there was some kind of heart risk, but forgot to ask my onc to go into detail about what it entails. She had me get an echocardiogram and an ekg before I started the combo and will do them every so often to keep tabs on my heart. Good to know it's a very small chance of this happening, but also kinda scary at the same time.

              ed williams
              Participant

                Thanks for the interesting article!!!Best Wishes!!!!Ed

                ed williams
                Participant

                  Thanks for the interesting article!!!Best Wishes!!!!Ed

                  ed williams
                  Participant

                    Thanks for the interesting article!!!Best Wishes!!!!Ed

                    MoiraM
                    Participant

                      As someone whose anterior pituitary gland was destroyed by ipi, I can't say I am surprised.

                      I really hope that they begin to get somewhere with tests to help predict how people will react to the immunotherapy drugs. Then they will be in a position to be appropriately hyper-vigilant for side effects.

                      Also I think it would be much better if they could predict if someone was a responder or not. I was told that my ipi treatment in the UK cost £80,000. Being generous with the response rate, only one-fifth of patients responded so that is £400,000 per 'success'. They could treat a lot more people, each of them in a much more appropriate way if they had such a test.

                       

                      MoiraM
                      Participant

                        As someone whose anterior pituitary gland was destroyed by ipi, I can't say I am surprised.

                        I really hope that they begin to get somewhere with tests to help predict how people will react to the immunotherapy drugs. Then they will be in a position to be appropriately hyper-vigilant for side effects.

                        Also I think it would be much better if they could predict if someone was a responder or not. I was told that my ipi treatment in the UK cost £80,000. Being generous with the response rate, only one-fifth of patients responded so that is £400,000 per 'success'. They could treat a lot more people, each of them in a much more appropriate way if they had such a test.

                         

                          ed williams
                          Participant

                            For your consideration Moira on the topic of being able to predict who will respond with Immunotherapy drugs, I have two videos for you. The first one from 2016 Grace presentation is pretty good and gives you the big picture.https://www.youtube.com/watch?v=5y1nnTsFBoE   The second video is from one of my favorite presenters, Dr.Charles Drake and if you go to the 50:00 min mark he gets into biomarkers and things to take into consideration with using pd-L1 as a biomarker .   https://www.youtube.com/watch?v=P4n_ePjlCFE   One of the points they make is how pd-l1 staining of a tumor sample is not an exact science, so imagine if you were pd-l1 positive and would qualify for specific Immunotherapy drug combination that works for 50% of people that take them and the 2 year survival % is in the high 88% range. But your sample of tissue is from a region of your tumor that doesn't meet the criteria, say 5% pd-l1 positive, and you are excluded from a chance to survive your cancer or at least buy time until some new and better combination is available. With the way Immunotherapy drug approvals have been advancing the last two years, I would think that very soon Ipi will be a secondary drug to Pd-1 for stage 3 patients or maybe used as a combination with Nivo for high risk stage 3 patients. Best wishes!!! Ed

                            ed williams
                            Participant

                              For your consideration Moira on the topic of being able to predict who will respond with Immunotherapy drugs, I have two videos for you. The first one from 2016 Grace presentation is pretty good and gives you the big picture.https://www.youtube.com/watch?v=5y1nnTsFBoE   The second video is from one of my favorite presenters, Dr.Charles Drake and if you go to the 50:00 min mark he gets into biomarkers and things to take into consideration with using pd-L1 as a biomarker .   https://www.youtube.com/watch?v=P4n_ePjlCFE   One of the points they make is how pd-l1 staining of a tumor sample is not an exact science, so imagine if you were pd-l1 positive and would qualify for specific Immunotherapy drug combination that works for 50% of people that take them and the 2 year survival % is in the high 88% range. But your sample of tissue is from a region of your tumor that doesn't meet the criteria, say 5% pd-l1 positive, and you are excluded from a chance to survive your cancer or at least buy time until some new and better combination is available. With the way Immunotherapy drug approvals have been advancing the last two years, I would think that very soon Ipi will be a secondary drug to Pd-1 for stage 3 patients or maybe used as a combination with Nivo for high risk stage 3 patients. Best wishes!!! Ed

                              MoiraM
                              Participant

                                Thank you!

                                Yes, the test needs to be much better than that.

                                For something like Ipi., which activates T cells, they need to be looking at the patient's immune system, not the tumour. 

                                I absolutely agree about Ipi being used in combination and finally superceded as a treatmnt or at least moved down the order. That is unless they work out how to protect patients from the more severe side effects.

                                As someone who refused to be admitted to hospital because of my phobia, Ipi was perfect. I  only had to commit to four half days in a treatment room in a clinic. And it worked! Now I 'watch and wait' to see if my 'complete response' is durable.

                                MoiraM
                                Participant

                                  Thank you!

                                  Yes, the test needs to be much better than that.

                                  For something like Ipi., which activates T cells, they need to be looking at the patient's immune system, not the tumour. 

                                  I absolutely agree about Ipi being used in combination and finally superceded as a treatmnt or at least moved down the order. That is unless they work out how to protect patients from the more severe side effects.

                                  As someone who refused to be admitted to hospital because of my phobia, Ipi was perfect. I  only had to commit to four half days in a treatment room in a clinic. And it worked! Now I 'watch and wait' to see if my 'complete response' is durable.

                                  MoiraM
                                  Participant

                                    Thank you!

                                    Yes, the test needs to be much better than that.

                                    For something like Ipi., which activates T cells, they need to be looking at the patient's immune system, not the tumour. 

                                    I absolutely agree about Ipi being used in combination and finally superceded as a treatmnt or at least moved down the order. That is unless they work out how to protect patients from the more severe side effects.

                                    As someone who refused to be admitted to hospital because of my phobia, Ipi was perfect. I  only had to commit to four half days in a treatment room in a clinic. And it worked! Now I 'watch and wait' to see if my 'complete response' is durable.

                                    SOLE
                                    Participant

                                      This would be my hope Ed. Nivo + ipi as adjuvant …

                                      SOLE
                                      Participant

                                        This would be my hope Ed. Nivo + ipi as adjuvant …

                                        SOLE
                                        Participant

                                          This would be my hope Ed. Nivo + ipi as adjuvant …

                                          ed williams
                                          Participant

                                            For your consideration Moira on the topic of being able to predict who will respond with Immunotherapy drugs, I have two videos for you. The first one from 2016 Grace presentation is pretty good and gives you the big picture.https://www.youtube.com/watch?v=5y1nnTsFBoE   The second video is from one of my favorite presenters, Dr.Charles Drake and if you go to the 50:00 min mark he gets into biomarkers and things to take into consideration with using pd-L1 as a biomarker .   https://www.youtube.com/watch?v=P4n_ePjlCFE   One of the points they make is how pd-l1 staining of a tumor sample is not an exact science, so imagine if you were pd-l1 positive and would qualify for specific Immunotherapy drug combination that works for 50% of people that take them and the 2 year survival % is in the high 88% range. But your sample of tissue is from a region of your tumor that doesn't meet the criteria, say 5% pd-l1 positive, and you are excluded from a chance to survive your cancer or at least buy time until some new and better combination is available. With the way Immunotherapy drug approvals have been advancing the last two years, I would think that very soon Ipi will be a secondary drug to Pd-1 for stage 3 patients or maybe used as a combination with Nivo for high risk stage 3 patients. Best wishes!!! Ed

                                          MoiraM
                                          Participant

                                            As someone whose anterior pituitary gland was destroyed by ipi, I can't say I am surprised.

                                            I really hope that they begin to get somewhere with tests to help predict how people will react to the immunotherapy drugs. Then they will be in a position to be appropriately hyper-vigilant for side effects.

                                            Also I think it would be much better if they could predict if someone was a responder or not. I was told that my ipi treatment in the UK cost £80,000. Being generous with the response rate, only one-fifth of patients responded so that is £400,000 per 'success'. They could treat a lot more people, each of them in a much more appropriate way if they had such a test.

                                             

                                            Bubbles
                                            Participant

                                              All important points to be sure.  For those of you interested…I just put up my latest rendition of side effects reported with immunotherapy: 

                                              http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2016/11/side-effects-to-immunotherapypart-6.html

                                              The abstract addressed in the NYT report by Moslehi and Sosman out of Vandy is included as well as another cardiotoxicity report out in August by Hodi et al. 

                                              All of the side effects addressed in my posts are very, to fairly, rare….though once you have them I'm sure they don't feel rare at all!!!  So…like I've said before…don't be frightened…but be smart and report any events or symptoms that are worrisome to your doc!!! 

                                              Wishing a good weekend to all!!  celeste

                                              Bubbles
                                              Participant

                                                All important points to be sure.  For those of you interested…I just put up my latest rendition of side effects reported with immunotherapy: 

                                                http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2016/11/side-effects-to-immunotherapypart-6.html

                                                The abstract addressed in the NYT report by Moslehi and Sosman out of Vandy is included as well as another cardiotoxicity report out in August by Hodi et al. 

                                                All of the side effects addressed in my posts are very, to fairly, rare….though once you have them I'm sure they don't feel rare at all!!!  So…like I've said before…don't be frightened…but be smart and report any events or symptoms that are worrisome to your doc!!! 

                                                Wishing a good weekend to all!!  celeste

                                                  MoiraM
                                                  Participant

                                                    The upside of being a complete responder to my ipi treatment  far outweighs losing all anterior pituitary gland function.

                                                    I would have the treatment again, even knowing the 'rare' downside I ended up with.

                                                    I always tell people to keep their doctors informed about all their symptoms.

                                                    I did that. It didn't make any difference. Please don't imply that all side effects that people who end up with the short straw weren't smart because that suggests that (a) they were stupid and (b) the side efffects are all avoidable.

                                                    MoiraM
                                                    Participant

                                                      The upside of being a complete responder to my ipi treatment  far outweighs losing all anterior pituitary gland function.

                                                      I would have the treatment again, even knowing the 'rare' downside I ended up with.

                                                      I always tell people to keep their doctors informed about all their symptoms.

                                                      I did that. It didn't make any difference. Please don't imply that all side effects that people who end up with the short straw weren't smart because that suggests that (a) they were stupid and (b) the side efffects are all avoidable.

                                                      Bubbles
                                                      Participant

                                                        Moira….so sorry that you were offended by my use of the word  "smart".  I was not at all implying that folks who had side effects were "dumb" or at fault somehow.  I was just trying not to frighten folks with a listing of some pretty scary side effects.  No one can tell who will get side effects and who won't.  But, I do know that lots of folks don't want to "bother" their doc or think maybe they are making something out of nothing.  I was merely trying to make sure that they tell their docs about anything that is worrying them.  And yes.  Even when they do tell their docs sometimes the outcome will not be changed.  However, sometimes it could save their life. c

                                                        Bubbles
                                                        Participant

                                                          Moira….so sorry that you were offended by my use of the word  "smart".  I was not at all implying that folks who had side effects were "dumb" or at fault somehow.  I was just trying not to frighten folks with a listing of some pretty scary side effects.  No one can tell who will get side effects and who won't.  But, I do know that lots of folks don't want to "bother" their doc or think maybe they are making something out of nothing.  I was merely trying to make sure that they tell their docs about anything that is worrying them.  And yes.  Even when they do tell their docs sometimes the outcome will not be changed.  However, sometimes it could save their life. c

                                                          Bubbles
                                                          Participant

                                                            Moira….so sorry that you were offended by my use of the word  "smart".  I was not at all implying that folks who had side effects were "dumb" or at fault somehow.  I was just trying not to frighten folks with a listing of some pretty scary side effects.  No one can tell who will get side effects and who won't.  But, I do know that lots of folks don't want to "bother" their doc or think maybe they are making something out of nothing.  I was merely trying to make sure that they tell their docs about anything that is worrying them.  And yes.  Even when they do tell their docs sometimes the outcome will not be changed.  However, sometimes it could save their life. c

                                                            MoiraM
                                                            Participant

                                                              The upside of being a complete responder to my ipi treatment  far outweighs losing all anterior pituitary gland function.

                                                              I would have the treatment again, even knowing the 'rare' downside I ended up with.

                                                              I always tell people to keep their doctors informed about all their symptoms.

                                                              I did that. It didn't make any difference. Please don't imply that all side effects that people who end up with the short straw weren't smart because that suggests that (a) they were stupid and (b) the side efffects are all avoidable.

                                                            Bubbles
                                                            Participant

                                                              All important points to be sure.  For those of you interested…I just put up my latest rendition of side effects reported with immunotherapy: 

                                                              http://chaoticallypreciselifeloveandmelanoma.blogspot.com/2016/11/side-effects-to-immunotherapypart-6.html

                                                              The abstract addressed in the NYT report by Moslehi and Sosman out of Vandy is included as well as another cardiotoxicity report out in August by Hodi et al. 

                                                              All of the side effects addressed in my posts are very, to fairly, rare….though once you have them I'm sure they don't feel rare at all!!!  So…like I've said before…don't be frightened…but be smart and report any events or symptoms that are worrisome to your doc!!! 

                                                              Wishing a good weekend to all!!  celeste

                                                              Mamapegela
                                                              Participant

                                                                Hi everyone-

                                                                The toxicity profile of Ipi is what has kept my oncologist from prescribing it as adjuvant therapy for stage 3.  Each time I have seen him I have pressed him about it with further questions, each time he has convinced me.  I know that many people here have had/are on Ipi for stage 3 and I have just wanted SO badly to do something!  But he keeps assuring me that if/when I progress to stage 4 I will have all those options open to me. 

                                                                My sincere hope is that everyone who is on Ipi now at stage 3 will have long term benefit and none- to -manageable side effects, and that those of us who are doing the "watchfull waiting" will be ok too.  Well.. one can hope right?

                                                                Actually in my case, we don't know what my stage is as those darn lung nodules keep growing slowly, slowly- but no new ones!).  I had another PET CT at University of Michigan yesterday, so awaiting results. 

                                                                By the way, has anyone else ever heard that there is a difference in the resolution/sensitivity of the stationary PET scanners and the mobile ones?  That is what my onc told me.  

                                                                Thanks for all of the ongoing education here.

                                                                Love and hope-

                                                                Peggy

                                                                Mamapegela
                                                                Participant

                                                                  Hi everyone-

                                                                  The toxicity profile of Ipi is what has kept my oncologist from prescribing it as adjuvant therapy for stage 3.  Each time I have seen him I have pressed him about it with further questions, each time he has convinced me.  I know that many people here have had/are on Ipi for stage 3 and I have just wanted SO badly to do something!  But he keeps assuring me that if/when I progress to stage 4 I will have all those options open to me. 

                                                                  My sincere hope is that everyone who is on Ipi now at stage 3 will have long term benefit and none- to -manageable side effects, and that those of us who are doing the "watchfull waiting" will be ok too.  Well.. one can hope right?

                                                                  Actually in my case, we don't know what my stage is as those darn lung nodules keep growing slowly, slowly- but no new ones!).  I had another PET CT at University of Michigan yesterday, so awaiting results. 

                                                                  By the way, has anyone else ever heard that there is a difference in the resolution/sensitivity of the stationary PET scanners and the mobile ones?  That is what my onc told me.  

                                                                  Thanks for all of the ongoing education here.

                                                                  Love and hope-

                                                                  Peggy

                                                                  Mamapegela
                                                                  Participant

                                                                    Hi everyone-

                                                                    The toxicity profile of Ipi is what has kept my oncologist from prescribing it as adjuvant therapy for stage 3.  Each time I have seen him I have pressed him about it with further questions, each time he has convinced me.  I know that many people here have had/are on Ipi for stage 3 and I have just wanted SO badly to do something!  But he keeps assuring me that if/when I progress to stage 4 I will have all those options open to me. 

                                                                    My sincere hope is that everyone who is on Ipi now at stage 3 will have long term benefit and none- to -manageable side effects, and that those of us who are doing the "watchfull waiting" will be ok too.  Well.. one can hope right?

                                                                    Actually in my case, we don't know what my stage is as those darn lung nodules keep growing slowly, slowly- but no new ones!).  I had another PET CT at University of Michigan yesterday, so awaiting results. 

                                                                    By the way, has anyone else ever heard that there is a difference in the resolution/sensitivity of the stationary PET scanners and the mobile ones?  That is what my onc told me.  

                                                                    Thanks for all of the ongoing education here.

                                                                    Love and hope-

                                                                    Peggy

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