Question for Jim Breitfeller

Thanks Jim (and Jewel). My brother is faced with making a similar decision and your input helps a lot.

By the way, does anyone know of any studies investigating the effect of combining Yervoy + IL-2? Is that a common treatment plan?

Thanks Jim (and Jewel). My brother is faced with making a similar decision and your input helps a lot.

By the way, does anyone know of any studies investigating the effect of combining Yervoy + IL-2? Is that a common treatment plan?

Thanks Jim (and Jewel). My brother is faced with making a similar decision and your input helps a lot.

By the way, does anyone know of any studies investigating the effect of combining Yervoy + IL-2? Is that a common treatment plan?

Pow, The response rate for the combination of Yervoy (Anti-CTLA-4) and IL-2 is about 22 %

Moving forward with immunotherapy: the rationale for anti-CTLA-4 therapy in melanoma

http://jco.imng.com/co/journal/articles/0507367.pdf 

Since both therapies are FDA approved, you should ask you Oncologist to about systematically combining the two therapies. Yervoy first, then IL-2 . Time Zero would be the time the first dose of Yervoy was delivered to the patient.

Approx. 50 days later, add the HD IL-2. This would be the maxium propagation time for the CD8 T-cells. Timing is everything.

It would be better if you could do a Clinical trial with Anti-PD-1 first because the half life of the drug is quite long. It is about a month.

Targeting PD-1/PD-L1 interactions for cancer immunotherapy 

http://www.landesbioscience.com/journals/oncoimmunology/article/21335/?show_full_text=true 

There is some data that sugests that there is a synergistic immune response when Yervoy (Anti-CTLA-4 and Anti-PD1 are used together.

Hi, Jim-

Wow! You really ARE an invaluable resource for us! Thank you so much for the excellent citations. I will read both of them carefully (and probably several times!) 

Your recommendations about the timing and synergy of anti-CTL4 and IL-2 are very helpful and exactly what I need. Do you have any citations for those recommendations?

The reason I ask is because my brother's VA oncologist is a great guy– smart, pleasant, willing, and sincerely concerned about his patients. However, being new to the VA, he is very reluctant to ruffle any feathers of the senior VA doctors. He is quick to prescribe and fight for any treatment that is already in the VA formulary. However, trying to do anything new and different (like combining Zelboraf and Yervoy as some private oncologists do) is out of the question. 

If I could give our nice, young oncologist published data that supports combining Yervoy + IL-2 (both of which are in the VA formulary), he might be willing to make a case to the department honchos.

My brother is going to look into available clinical trials before starting Yervoy. But if he can't get into a trial, it looks as though combining Yervoy and IL-2 could be better than Yervoy alone. I would very much appreciate anything you could give me that supports that approach. 

Cytotoxic T lymphocyte-associated antigen 4 blockade with ipilimumab: Long-term follow-up of 179 patients with metastatic melanoma.

Print this page

http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=74&abstractID=53615 

Background: We have previously shown objective clinical responses in patients with metastatic melanoma treated with CTLA-4 blockade using ipilimumab. We have treated 179 patients in 3 separate clinical trials and now have long-term follow-up to evaluate the durability and unique features of this immunotherapy. Methods: A total of 179 patients with metastatic melanoma were treated in 3 trials: In Protocol 1, 56 patients received ipilimumab with gp100 peptide vaccines. In Protocol 2, 36 patients received ipilimumab with high-dose interleukin-2 (IL-2). In Protocol 3, 87 patients received intra-patient dose escalation of ipilimumab and were randomized to receive gp100 peptides. We have updated and analyzed the follow-up and survival data for these trials. Results: With median follow-up for Protocol 1, 2, and 3 being 80, 71, and 60 months, median survival was 15, 16, and 13 months, respectively. Objective tumor regression was 12% for Protocol 1, 25% for Protocol 2, and 21% for Protocol 3. Patients in Protocol 2 had a 17% complete response rate (6 patients: 77+, 74+, 72+, 71+, 71+, and 69+ months), as compared to 7% in Protocol 1 (4 patients: 82+, 81+, 79+, and 66+ months) and 8% in Protocol 3 (5 patients: 64+, 63+, 62+, 60+, and 55+ months); all complete responses are ongoing. Many patients who eventually became complete responders had continual tumor shrinkage after stopping therapy. Conclusions: CTLA-4 blockade with ipilimumab can achieve durable objective tumor regression in patients with metastatic melanoma. The combination of ipilimumab and IL-2 appears to have an increased complete response rate, although this needs to be tested in a prospective randomized trial. This report represents the largest single-institution experience with the longest follow-up for this agent; our results support its role as a viable treatment option for patients with metastatic melanoma. 

You want a complete response!!!!!  All signs of cancer are gone. You may be CURED!!!!!

Jimmy B

That's perfect, Jim! Thank you! I requested a reprint of the complete article and I will send it to my brother's oncologist. Hopefully, he will mull it over between now and the time that IL-2 should be administered.

Speaking of time to administer IL-2… where did you get the number "50 days after starting ipilimumab"? Since you think that this timing is critical, it would be good for the oncologist to see something about that, too.

 Thank you so much for being such a big help!

That's perfect, Jim! Thank you! I requested a reprint of the complete article and I will send it to my brother's oncologist. Hopefully, he will mull it over between now and the time that IL-2 should be administered.

Speaking of time to administer IL-2… where did you get the number "50 days after starting ipilimumab"? Since you think that this timing is critical, it would be good for the oncologist to see something about that, too.

 Thank you so much for being such a big help!

POW,

Actually, In my own Treatment I documented my treatments as if I doing a research paper. I wrote everything down including Dates, Timing of drugs and how I felt. It turned into a research paper called "Melanoma and the Magic bullet, Anti-CTLA-4". I also found some references in a paper called

Autologous Tumor Specific Cytotoxic Lymphocytes in the Infiltrate of Human Metastatic Melanomas  Activation by Interleukin 2 and Autologous Tumor Cells, and Involvement of the T Cell Receptor[published J . Exp. MED.  The RockefellerUniversityPress. 1988 Oct 1;Vol 168 October 1988 1419-1441

http://jem.rupress.org/cgi/reprint/168/4/1419.pdf

By: Itoh, K; Platsoucas, CD; Balch, CM 

This timing of the Maxium propagation time of 50 days for T-cells. If you add the IL-2 in the growth phase, you will grow the unwanted T-Regulatory cells that suppress the T-cells by secreting IL-10 and upregulating of the CTLA-4 and PD-1 receptors that are used by the immune system as checkpoint  modulators.

Also, Dr. Jedd Wolchok did some studies monitoring the Absoute Lymphocyte counts (ALC) and found that of the count doubled by the 7 week (49 days) after administering Yervoy, the patient seem to have clinical benefit.

It was also discovered that it was better to add IL-2 durning the contraction phase of the T-cells. So that would be 50 daysor so  after activation. This was bsed on a paper from Blattman.

"Therapeutic use of IL-2 to enhance antiviral T- cells responces in vivo"

https://www.box.net/shared/109rgqkvqd 

I hope this helps

Jimmy B

POW,

Actually, In my own Treatment I documented my treatments as if I doing a research paper. I wrote everything down including Dates, Timing of drugs and how I felt. It turned into a research paper called "Melanoma and the Magic bullet, Anti-CTLA-4". I also found some references in a paper called

Autologous Tumor Specific Cytotoxic Lymphocytes in the Infiltrate of Human Metastatic Melanomas  Activation by Interleukin 2 and Autologous Tumor Cells, and Involvement of the T Cell Receptor[published J . Exp. MED.  The RockefellerUniversityPress. 1988 Oct 1;Vol 168 October 1988 1419-1441

http://jem.rupress.org/cgi/reprint/168/4/1419.pdf

By: Itoh, K; Platsoucas, CD; Balch, CM 

This timing of the Maxium propagation time of 50 days for T-cells. If you add the IL-2 in the growth phase, you will grow the unwanted T-Regulatory cells that suppress the T-cells by secreting IL-10 and upregulating of the CTLA-4 and PD-1 receptors that are used by the immune system as checkpoint  modulators.

Also, Dr. Jedd Wolchok did some studies monitoring the Absoute Lymphocyte counts (ALC) and found that of the count doubled by the 7 week (49 days) after administering Yervoy, the patient seem to have clinical benefit.

It was also discovered that it was better to add IL-2 durning the contraction phase of the T-cells. So that would be 50 daysor so  after activation. This was bsed on a paper from Blattman.

"Therapeutic use of IL-2 to enhance antiviral T- cells responces in vivo"

https://www.box.net/shared/109rgqkvqd 

I hope this helps

Jimmy B

Very impressive! And very helpful!

Thanks so much!

Very impressive! And very helpful!

Thanks so much!

Very impressive! And very helpful!

Thanks so much!

POW,

Actually, In my own Treatment I documented my treatments as if I doing a research paper. I wrote everything down including Dates, Timing of drugs and how I felt. It turned into a research paper called "Melanoma and the Magic bullet, Anti-CTLA-4". I also found some references in a paper called

Autologous Tumor Specific Cytotoxic Lymphocytes in the Infiltrate of Human Metastatic Melanomas  Activation by Interleukin 2 and Autologous Tumor Cells, and Involvement of the T Cell Receptor[published J . Exp. MED.  The RockefellerUniversityPress. 1988 Oct 1;Vol 168 October 1988 1419-1441

http://jem.rupress.org/cgi/reprint/168/4/1419.pdf

By: Itoh, K; Platsoucas, CD; Balch, CM 

This timing of the Maxium propagation time of 50 days for T-cells. If you add the IL-2 in the growth phase, you will grow the unwanted T-Regulatory cells that suppress the T-cells by secreting IL-10 and upregulating of the CTLA-4 and PD-1 receptors that are used by the immune system as checkpoint  modulators.

Also, Dr. Jedd Wolchok did some studies monitoring the Absoute Lymphocyte counts (ALC) and found that of the count doubled by the 7 week (49 days) after administering Yervoy, the patient seem to have clinical benefit.

It was also discovered that it was better to add IL-2 durning the contraction phase of the T-cells. So that would be 50 daysor so  after activation. This was bsed on a paper from Blattman.

"Therapeutic use of IL-2 to enhance antiviral T- cells responces in vivo"

https://www.box.net/shared/109rgqkvqd 

I hope this helps

Jimmy B

That's perfect, Jim! Thank you! I requested a reprint of the complete article and I will send it to my brother's oncologist. Hopefully, he will mull it over between now and the time that IL-2 should be administered.

Speaking of time to administer IL-2… where did you get the number "50 days after starting ipilimumab"? Since you think that this timing is critical, it would be good for the oncologist to see something about that, too.

 Thank you so much for being such a big help!

Cytotoxic T lymphocyte-associated antigen 4 blockade with ipilimumab: Long-term follow-up of 179 patients with metastatic melanoma.

Print this page

http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=74&abstractID=53615 

Background: We have previously shown objective clinical responses in patients with metastatic melanoma treated with CTLA-4 blockade using ipilimumab. We have treated 179 patients in 3 separate clinical trials and now have long-term follow-up to evaluate the durability and unique features of this immunotherapy. Methods: A total of 179 patients with metastatic melanoma were treated in 3 trials: In Protocol 1, 56 patients received ipilimumab with gp100 peptide vaccines. In Protocol 2, 36 patients received ipilimumab with high-dose interleukin-2 (IL-2). In Protocol 3, 87 patients received intra-patient dose escalation of ipilimumab and were randomized to receive gp100 peptides. We have updated and analyzed the follow-up and survival data for these trials. Results: With median follow-up for Protocol 1, 2, and 3 being 80, 71, and 60 months, median survival was 15, 16, and 13 months, respectively. Objective tumor regression was 12% for Protocol 1, 25% for Protocol 2, and 21% for Protocol 3. Patients in Protocol 2 had a 17% complete response rate (6 patients: 77+, 74+, 72+, 71+, 71+, and 69+ months), as compared to 7% in Protocol 1 (4 patients: 82+, 81+, 79+, and 66+ months) and 8% in Protocol 3 (5 patients: 64+, 63+, 62+, 60+, and 55+ months); all complete responses are ongoing. Many patients who eventually became complete responders had continual tumor shrinkage after stopping therapy. Conclusions: CTLA-4 blockade with ipilimumab can achieve durable objective tumor regression in patients with metastatic melanoma. The combination of ipilimumab and IL-2 appears to have an increased complete response rate, although this needs to be tested in a prospective randomized trial. This report represents the largest single-institution experience with the longest follow-up for this agent; our results support its role as a viable treatment option for patients with metastatic melanoma. 

You want a complete response!!!!!  All signs of cancer are gone. You may be CURED!!!!!

Jimmy B

Cytotoxic T lymphocyte-associated antigen 4 blockade with ipilimumab: Long-term follow-up of 179 patients with metastatic melanoma.

Print this page

http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=74&abstractID=53615 

Background: We have previously shown objective clinical responses in patients with metastatic melanoma treated with CTLA-4 blockade using ipilimumab. We have treated 179 patients in 3 separate clinical trials and now have long-term follow-up to evaluate the durability and unique features of this immunotherapy. Methods: A total of 179 patients with metastatic melanoma were treated in 3 trials: In Protocol 1, 56 patients received ipilimumab with gp100 peptide vaccines. In Protocol 2, 36 patients received ipilimumab with high-dose interleukin-2 (IL-2). In Protocol 3, 87 patients received intra-patient dose escalation of ipilimumab and were randomized to receive gp100 peptides. We have updated and analyzed the follow-up and survival data for these trials. Results: With median follow-up for Protocol 1, 2, and 3 being 80, 71, and 60 months, median survival was 15, 16, and 13 months, respectively. Objective tumor regression was 12% for Protocol 1, 25% for Protocol 2, and 21% for Protocol 3. Patients in Protocol 2 had a 17% complete response rate (6 patients: 77+, 74+, 72+, 71+, 71+, and 69+ months), as compared to 7% in Protocol 1 (4 patients: 82+, 81+, 79+, and 66+ months) and 8% in Protocol 3 (5 patients: 64+, 63+, 62+, 60+, and 55+ months); all complete responses are ongoing. Many patients who eventually became complete responders had continual tumor shrinkage after stopping therapy. Conclusions: CTLA-4 blockade with ipilimumab can achieve durable objective tumor regression in patients with metastatic melanoma. The combination of ipilimumab and IL-2 appears to have an increased complete response rate, although this needs to be tested in a prospective randomized trial. This report represents the largest single-institution experience with the longest follow-up for this agent; our results support its role as a viable treatment option for patients with metastatic melanoma. 

You want a complete response!!!!!  All signs of cancer are gone. You may be CURED!!!!!

Jimmy B

Hi, Jim-

Wow! You really ARE an invaluable resource for us! Thank you so much for the excellent citations. I will read both of them carefully (and probably several times!) 

Your recommendations about the timing and synergy of anti-CTL4 and IL-2 are very helpful and exactly what I need. Do you have any citations for those recommendations?

The reason I ask is because my brother's VA oncologist is a great guy– smart, pleasant, willing, and sincerely concerned about his patients. However, being new to the VA, he is very reluctant to ruffle any feathers of the senior VA doctors. He is quick to prescribe and fight for any treatment that is already in the VA formulary. However, trying to do anything new and different (like combining Zelboraf and Yervoy as some private oncologists do) is out of the question. 

If I could give our nice, young oncologist published data that supports combining Yervoy + IL-2 (both of which are in the VA formulary), he might be willing to make a case to the department honchos.

My brother is going to look into available clinical trials before starting Yervoy. But if he can't get into a trial, it looks as though combining Yervoy and IL-2 could be better than Yervoy alone. I would very much appreciate anything you could give me that supports that approach. 

Hi, Jim-

Wow! You really ARE an invaluable resource for us! Thank you so much for the excellent citations. I will read both of them carefully (and probably several times!) 

Your recommendations about the timing and synergy of anti-CTL4 and IL-2 are very helpful and exactly what I need. Do you have any citations for those recommendations?

The reason I ask is because my brother's VA oncologist is a great guy– smart, pleasant, willing, and sincerely concerned about his patients. However, being new to the VA, he is very reluctant to ruffle any feathers of the senior VA doctors. He is quick to prescribe and fight for any treatment that is already in the VA formulary. However, trying to do anything new and different (like combining Zelboraf and Yervoy as some private oncologists do) is out of the question. 

If I could give our nice, young oncologist published data that supports combining Yervoy + IL-2 (both of which are in the VA formulary), he might be willing to make a case to the department honchos.

My brother is going to look into available clinical trials before starting Yervoy. But if he can't get into a trial, it looks as though combining Yervoy and IL-2 could be better than Yervoy alone. I would very much appreciate anything you could give me that supports that approach. 

Pow, The response rate for the combination of Yervoy (Anti-CTLA-4) and IL-2 is about 22 %

Moving forward with immunotherapy: the rationale for anti-CTLA-4 therapy in melanoma

http://jco.imng.com/co/journal/articles/0507367.pdf 

Since both therapies are FDA approved, you should ask you Oncologist to about systematically combining the two therapies. Yervoy first, then IL-2 . Time Zero would be the time the first dose of Yervoy was delivered to the patient.

Approx. 50 days later, add the HD IL-2. This would be the maxium propagation time for the CD8 T-cells. Timing is everything.

It would be better if you could do a Clinical trial with Anti-PD-1 first because the half life of the drug is quite long. It is about a month.

Targeting PD-1/PD-L1 interactions for cancer immunotherapy 

http://www.landesbioscience.com/journals/oncoimmunology/article/21335/?show_full_text=true 

There is some data that sugests that there is a synergistic immune response when Yervoy (Anti-CTLA-4 and Anti-PD1 are used together.

Pow, The response rate for the combination of Yervoy (Anti-CTLA-4) and IL-2 is about 22 %

Moving forward with immunotherapy: the rationale for anti-CTLA-4 therapy in melanoma

http://jco.imng.com/co/journal/articles/0507367.pdf 

Since both therapies are FDA approved, you should ask you Oncologist to about systematically combining the two therapies. Yervoy first, then IL-2 . Time Zero would be the time the first dose of Yervoy was delivered to the patient.

Approx. 50 days later, add the HD IL-2. This would be the maxium propagation time for the CD8 T-cells. Timing is everything.

It would be better if you could do a Clinical trial with Anti-PD-1 first because the half life of the drug is quite long. It is about a month.

Targeting PD-1/PD-L1 interactions for cancer immunotherapy 

http://www.landesbioscience.com/journals/oncoimmunology/article/21335/?show_full_text=true 

There is some data that sugests that there is a synergistic immune response when Yervoy (Anti-CTLA-4 and Anti-PD1 are used together.

Jewel,

If you do the SOC first, It may disqualify you from the clinical trials later.

I would look for trials with DC vaccines + Anti-PD-1 or Yervoy as my first choice.

Best regards

Jimmy b

Jewel,

If you do the SOC first, It may disqualify you from the clinical trials later.

I would look for trials with DC vaccines + Anti-PD-1 or Yervoy as my first choice.

Best regards

Jimmy b

Jewel,

If you do the SOC first, It may disqualify you from the clinical trials later.

I would look for trials with DC vaccines + Anti-PD-1 or Yervoy as my first choice.

Best regards

Jimmy b