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Please help – IL2 after Ipi?
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Please help – IL2 after Ipi?

› Forums › General Melanoma Community › Please help – IL2 after Ipi?

  • Post
    • September 15, 2011 at 12:30 pm
    Gracie
    Participant

      I am scheduled to begin IL2 Monday morn.  I was on the ipi/placibo trial study for 14 months with minimal side effects if any, as Stage 3b.  I had no tumors till now.  Presently I have 2, one in lung, one on chest wall.  I was unblinded today and yes, I was getting the ipi.  I guess you would say, "I am not a responder."  So now we try IL2.  My doc says that the side effects will be more intense coming from the ipi, possible bowl perferation.  I will have a colonoscopy tomorrow to check for weaknesses or inflamation

      I am scheduled to begin IL2 Monday morn.  I was on the ipi/placibo trial study for 14 months with minimal side effects if any, as Stage 3b.  I had no tumors till now.  Presently I have 2, one in lung, one on chest wall.  I was unblinded today and yes, I was getting the ipi.  I guess you would say, "I am not a responder."  So now we try IL2.  My doc says that the side effects will be more intense coming from the ipi, possible bowl perferation.  I will have a colonoscopy tomorrow to check for weaknesses or inflamation in bowel from ipi and treat colon with steroids for two weeks before IL2 if necessary. Doc has been attempting to talk to mel oncologists around country with patients on IL2 from ipi.  I was hoping to hear from someone on the board sooner.  I am having second thoughts about doing IL2.

      Have any of you experienced IL2 after ipi?

      How were the side effects for you?  perhaps more intense?

      Were you a responder to IL2?  (Doc said it was more my "chemestry" that prevented me from responding rather than a "shelf life" of ipi over 14 months)

      does anyone know if you don't respond to ipi you are as likely to not respond to IL2?

      Has anyone experienced a bowl perferation and what is the long term repercussion?

      I am very thankful for this board and all of you…a safe place to go during this time when I lay awake at night thinking of questions I forgot to ask doc. 

      Gracie, stage 4

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    • Replies
        • September 15, 2011 at 2:38 pm
        jim Breitfeller
        Participant

          Gracie,

          Answers to your questions.

          Have any of you experienced IL2 after ipi?

          Yes!! I did one dose of 15mg/Kg of  Tremelimumab(from Pfizer) is an IgG2

          A different formulation than Ipi.

          How were the side effects for you?  I had very low effects from Tremelimumab,

          perhaps more intense? For IL-2, I had cell leakage, Headaches, rash/ itching and finally a heart attack which stopped my IL-2 therapy after 3 cycles.

          Were you a responder to IL2?  Yes,  I had a complete resonse.

          See my paper called Melanoma and the magic Bullet

          http://www.box.net/shared/kjgr6dkztj

          My story starts on page 16.

          (Doc said it was more my "chemestry" that prevented me from responding rather than a "shelf life" of ipi over 14 months)

          does anyone know if you don't respond to ipi you are as likely to not respond to IL2?

          You did not respond to Ipi because you are missing a signal (The Danger Signal)

          This tells you immune system that there is a invader inside you. Hopefully you have tumor specific antigens being presented on the APCs  Antigen Presenting Cells.

          Also, if your T-cells don't produce enough IL-2 after activation, and the Tregs will compete for the IL-2 and usually win.  No activation is seen and the immune is unresponsive.

           

          Has anyone experienced a bowl perferation and what is the long term repercussion? No, but is not good. Toxic watse enters you body. If bowl perferation occurs, death may happen.

          Gracie, if you want to contact me off-line my email is [email protected]

          I wish you all the best

          jimmy b

            • September 16, 2011 at 12:49 am
            Lisa13
            Participant

              Hi Jimmy,

              You said that Gracie may not have responded to ipi because she was missing a signal or perhaps lacking IL-2.  That being said, do Dr's even know why some respond to it and some don't?  I also recall you and my Dr both suggesting that if your Absolute Lymphocyte count doubles by week 7, then the drug may work for you – is this right?    

              Thanks,

              Lisa – Stage 4

              • September 16, 2011 at 10:31 am
              jim Breitfeller
              Participant

                Lisa,

                If your Absolute Lymphocyte count doubles by week 7, means that your immune system is activated and the your T-cells are multiplying.

                There are many reasons why Ipi is not working,

                1) not enough antigens displayed on the (APCs) antigen presenting cells

                2) Suboptimal amounts of IL-2 during priming promoted apoptosis, little proliferation and cell cycling, yet the CD8+ effectors generated produced high levels of cytokines and proliferated autonomously. This is the reason why it takes a while for the Tumors to begin to shrink because of little proliferation. If you have large tumor burden, then the Tregs grab all the IL-2 and shuts down the immune response

                3) T-regulation cells (Tregs) are controlling  the immune response by the up-regulation of the the CTLA-4 receptor and the secretion of surpressive cytokines like IL-10.

                4)  The T-cells are not getting though the tumor's microenviroment. The wrong ckyokine mixture.

                 

                I hope this answers your question

                 

                Jimmy B

                • September 16, 2011 at 10:31 am
                jim Breitfeller
                Participant

                  Lisa,

                  If your Absolute Lymphocyte count doubles by week 7, means that your immune system is activated and the your T-cells are multiplying.

                  There are many reasons why Ipi is not working,

                  1) not enough antigens displayed on the (APCs) antigen presenting cells

                  2) Suboptimal amounts of IL-2 during priming promoted apoptosis, little proliferation and cell cycling, yet the CD8+ effectors generated produced high levels of cytokines and proliferated autonomously. This is the reason why it takes a while for the Tumors to begin to shrink because of little proliferation. If you have large tumor burden, then the Tregs grab all the IL-2 and shuts down the immune response

                  3) T-regulation cells (Tregs) are controlling  the immune response by the up-regulation of the the CTLA-4 receptor and the secretion of surpressive cytokines like IL-10.

                  4)  The T-cells are not getting though the tumor's microenviroment. The wrong ckyokine mixture.

                   

                  I hope this answers your question

                   

                  Jimmy B

                  • September 16, 2011 at 12:49 am
                  Lisa13
                  Participant

                    Hi Jimmy,

                    You said that Gracie may not have responded to ipi because she was missing a signal or perhaps lacking IL-2.  That being said, do Dr's even know why some respond to it and some don't?  I also recall you and my Dr both suggesting that if your Absolute Lymphocyte count doubles by week 7, then the drug may work for you – is this right?    

                    Thanks,

                    Lisa – Stage 4

                  • September 15, 2011 at 2:38 pm
                  jim Breitfeller
                  Participant

                    Gracie,

                    Answers to your questions.

                    Have any of you experienced IL2 after ipi?

                    Yes!! I did one dose of 15mg/Kg of  Tremelimumab(from Pfizer) is an IgG2

                    A different formulation than Ipi.

                    How were the side effects for you?  I had very low effects from Tremelimumab,

                    perhaps more intense? For IL-2, I had cell leakage, Headaches, rash/ itching and finally a heart attack which stopped my IL-2 therapy after 3 cycles.

                    Were you a responder to IL2?  Yes,  I had a complete resonse.

                    See my paper called Melanoma and the magic Bullet

                    http://www.box.net/shared/kjgr6dkztj

                    My story starts on page 16.

                    (Doc said it was more my "chemestry" that prevented me from responding rather than a "shelf life" of ipi over 14 months)

                    does anyone know if you don't respond to ipi you are as likely to not respond to IL2?

                    You did not respond to Ipi because you are missing a signal (The Danger Signal)

                    This tells you immune system that there is a invader inside you. Hopefully you have tumor specific antigens being presented on the APCs  Antigen Presenting Cells.

                    Also, if your T-cells don't produce enough IL-2 after activation, and the Tregs will compete for the IL-2 and usually win.  No activation is seen and the immune is unresponsive.

                     

                    Has anyone experienced a bowl perferation and what is the long term repercussion? No, but is not good. Toxic watse enters you body. If bowl perferation occurs, death may happen.

                    Gracie, if you want to contact me off-line my email is [email protected]

                    I wish you all the best

                    jimmy b

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