› Forums › General Melanoma Community › Yervoy/IPI side effects questions
- This topic has 12 replies, 4 voices, and was last updated 14 years, 5 months ago by
MichaelFL.
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- August 1, 2011 at 6:16 pm
Hi all,
I have a close family member who is Stage IV melanoma, and I have some questions about Yervoy and its side effects. Any feedback would be appreciated. Thank you very much!
1. Is it good to get side effects, particularly diarrhea? And is it better to get them quickly? I understand the side effects can be difficult to deal with and even dangerous, but do they mean that there is a better chance the ipi is working? If so, could you point me to info/data/studies/reports on this?
Hi all,
I have a close family member who is Stage IV melanoma, and I have some questions about Yervoy and its side effects. Any feedback would be appreciated. Thank you very much!
1. Is it good to get side effects, particularly diarrhea? And is it better to get them quickly? I understand the side effects can be difficult to deal with and even dangerous, but do they mean that there is a better chance the ipi is working? If so, could you point me to info/data/studies/reports on this?
2. If you get diarrhea and then are given a corticosteroid (prednisone) to counter-act those effects, does the prednisone act to partially/completely reduce the efficacy of the ipi?
3. Can the ipi and/or prednisone be a reasonable explanation for unexplained and very sharp and debilitating hip pain in one hip? (This one hip also has an artificial replacement.) A team of doctors (oncologists, surgeons, hip experts) have ruled out the patient's melanoma as the cause. Tests run for this include X-Rays, MRI, bone scan.
(Any cites to news or journal articles, etc., would be appreciated.)
Thank you very much! From reading the posts here, this is a wonderful community, and I wish everyone the best.
Ray
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- August 1, 2011 at 8:25 pm
Ray,
If you would update your profile, the very knowledgeable folks on this board will begin to chime in.
It's a bit hard to answer not knowing age, other health issues, etc?
Best of luck, this is the kindest place in the world.
TracyLee
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- August 1, 2011 at 9:02 pm
Thanks, TracyLee. I am fairly new here 🙂
I've updated my profile. The patient is my father, 68 years old. The initial tumor was on his temple (8mm, so rather large), and he had it surgically removed in May 2009. No sign of spread at the time. In December 2011 we learned the melanoma had metastasized to his lung, liver, spine, pelvis, and hip. The tumor in his spine fractured his vertebrae and he needed surgery to correct that, during which time the surgeon removed what he could from the spine. The rest they radiated. The oncologist guesses the metastasis occurred in May of 2010.
He's been through a round of Abraxane/Avastin, which reduced or removed the lung tumors and kept everything else stable but didn't help his liver. Went on ipi/dacarbazine in April 2011. He had some diarrhea issues on the ipi, which developed fairly quickly after the first ipi infusion, and they gave him prednisone (started with 80 mg and then reduced to 5). He got three ipi infusions but wasn't able to complete the fourth in the 16 week period because of the diarrhea issues.
The indication right now is that the disease is stable. But he's had horrible, debilitating pain in one of his hips for 6 weeks, and the doctors can't figure out why (but do not think it is cancer-related; they've done x-rays, MRI, bone scan). I am wondering whether the hip pain might be related to the ipi and/or prednisone. Also at issue is that he had a hip replacement in the same hip about four years ago. I don't know if that's related, but his hip surgeon (as with the other doctors) said that from the x-rays, the hip replacement appears to be in place and just fine. He's lost 40 pounds through the treatments.
That's the background of the situation. I look forward to any replies.
Best,
Ray
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- August 1, 2011 at 9:02 pm
Thanks, TracyLee. I am fairly new here 🙂
I've updated my profile. The patient is my father, 68 years old. The initial tumor was on his temple (8mm, so rather large), and he had it surgically removed in May 2009. No sign of spread at the time. In December 2011 we learned the melanoma had metastasized to his lung, liver, spine, pelvis, and hip. The tumor in his spine fractured his vertebrae and he needed surgery to correct that, during which time the surgeon removed what he could from the spine. The rest they radiated. The oncologist guesses the metastasis occurred in May of 2010.
He's been through a round of Abraxane/Avastin, which reduced or removed the lung tumors and kept everything else stable but didn't help his liver. Went on ipi/dacarbazine in April 2011. He had some diarrhea issues on the ipi, which developed fairly quickly after the first ipi infusion, and they gave him prednisone (started with 80 mg and then reduced to 5). He got three ipi infusions but wasn't able to complete the fourth in the 16 week period because of the diarrhea issues.
The indication right now is that the disease is stable. But he's had horrible, debilitating pain in one of his hips for 6 weeks, and the doctors can't figure out why (but do not think it is cancer-related; they've done x-rays, MRI, bone scan). I am wondering whether the hip pain might be related to the ipi and/or prednisone. Also at issue is that he had a hip replacement in the same hip about four years ago. I don't know if that's related, but his hip surgeon (as with the other doctors) said that from the x-rays, the hip replacement appears to be in place and just fine. He's lost 40 pounds through the treatments.
That's the background of the situation. I look forward to any replies.
Best,
Ray
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- August 1, 2011 at 10:07 pm
I can't go based on experience, but I can tell you what I have read online and here.
To try and answer your questions:
#1 The diarrhea is the #1 side effect of Yervoy, so it does not mean that to have it is indicative of a response.
#2 From what I have read, a steroid (prednisone) does not affect yervoy, but should still be tapered if/when things are more manageable.
#3 Not really sure I can answer as everyone is different.
Also, do you know if your fathers ALC (absolute Lymphocyte Count) increased? From what I have read, if the level is over 1,000 by the second dose of ipilimumab, there is a >5% chance of response and they may be considered a responder. Also, some side effects that I have heard of on the board that do indicate a response are white hair, facial hair or beard.
Read on:
Published Online: 8 Feb 2010 Copyright © 2010 American Cancer Society
Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting.
lymphocyte count after 2 doses correlates with survival
Results: A total of 53 patients were enrolled, with 51 evaluable. Grade 3/4 immune-related adverse events were noted in 29% of patients, with the most common immune-related adverse events being pruritus (43%), rash (37%), and diarrhea (33%). On the basis of immune-related response criteria, the response rate (CR + PR) was 12% (95% confidence interval [CI], 5%-25%), whereas 29% had SD (95% CI, 18%-44%). The median progression-free survival was 2.6 months (95% CI, 2.3-5.2 months), whereas the median overall survival (OS) was 7.2 months (95% CI, 4.0-13.3 months). Patients with an absolute lymphocyte count (ALC) 1000/L after 2 ipilimumab treatments (Week 7) had a significantly improved clinical benefit rate (51% vs 0%; P = .01) and median OS (11.9 vs 1.4 months; P < .001) compared with those with an ALC <1000/l
Conclusion: The results confirm that ipilimumab is clinically active in patients with advanced refractory melanoma. The ALC after 2 ipilimumab treatments appears to correlate with clinical benefit and OS, and should be prospectively validated.
I have also read on other sites that side effects occur in up to 84% of patients and the most common side effects of ipilimumab occur in the gastrointestinal tract (such as diarrhea and inflammation of the colon) and the skin (such as rash and inflammation of the skin). Less frequently occurring side effects include hepatitis, inflammation of the pituitary gland (hypophysitis), eye inflammation (uveitis), and kidney problems (nephritis).
Here is a link to a study which shows the response rate and side effects:
From: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(09)70334-1/abstract
February, 2010.
Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomized, double-blind, multicentre, phase 2, dose-ranging study.
Findings:
The best overall response rate was 11·1% for 10 mg/kg, 4·2% for 3 mg/kg, and 0% for 0·3 mg/kg. Immune-related adverse events of any grade arose in 50 of 71, 46 of 71, and 19 of 72 patients at doses of 10 mg/kg, 3 mg/kg, and 0·3 mg/kg, respectively; the most common grade 3—4 adverse events were gastrointestinal immune-related events (11 in the 10 mg/kg group, two in the 3 mg/kg group, none in the 0·3 mg/kg group) and diarrhea (ten in the 10 mg/kg group, one in the 3 mg/kg group, none in the 0·3 mg/kg group).
In another study:
http://knol.google.com/k/krishan-maggon/ipilimumab-bms-review-a-cancer/3fy5eowy8suq3/107#
In a Phase II trial in 155 patients with pretreated stage III or stage IV melanoma, the best overall response rate (modified WHO criteria) was 5.8% short of 10% minimum required by FDA. The disease was controlled in 27% of patients treated with 10 mg/kg induction (4 cycles) and maintenance doses. The survival at 1 year was 47% and at 2 year 33%. Forty three patients had progressive disease. Adverse drug reactions were immune related, 19% patients had Grade 3 and 3.2% Grade 4 dermatological and gastrointestinal toxicity. In a compassionate use trial in MSKC in advanced refractory patients, 53 patients were enrolled and 51 were eligible for analysis. grade 3 toxicity was reported by 29% of patients, 12% of patients had tumor response (CR+PR) and 29% had stable disease. Overall survival in this group was 7.2 months and progression free survival was 2.6 months.
Best wishes,
Michael
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- August 1, 2011 at 10:46 pm
Hi,
It's not prednisone they use for the diarhhea, because that effects the enire system; rather they use a steriod called Entocort (just came off patent, generic is Budesonide).
It's not whether one gets side effects early, as many do not present until after 2 or 3 infusions. My diarhhea started very early, about 10 days after my 1st infusion; my rash started after my 3rd infusion, and boy does it itch. The doctor prescribed Doxepin (brand: Sinequan) which is an old-time antidepressant. It relieves rash/itch better than all the cremes & antihistimes put together. It does cause low blood pressure, so one has to start very slowly, 1 at night for 5 nights, if tolerated, add one in the a.m, if tolerated add third dose. I'm on the 3 pills/day. When I got the rash, my doctor was happy…it seems that the diahrrea is very common, but when we start getting more side-effects, they believe that it is the body showing an immune response.
Hope this helps,
karen
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- August 1, 2011 at 10:46 pm
Hi,
It's not prednisone they use for the diarhhea, because that effects the enire system; rather they use a steriod called Entocort (just came off patent, generic is Budesonide).
It's not whether one gets side effects early, as many do not present until after 2 or 3 infusions. My diarhhea started very early, about 10 days after my 1st infusion; my rash started after my 3rd infusion, and boy does it itch. The doctor prescribed Doxepin (brand: Sinequan) which is an old-time antidepressant. It relieves rash/itch better than all the cremes & antihistimes put together. It does cause low blood pressure, so one has to start very slowly, 1 at night for 5 nights, if tolerated, add one in the a.m, if tolerated add third dose. I'm on the 3 pills/day. When I got the rash, my doctor was happy…it seems that the diahrrea is very common, but when we start getting more side-effects, they believe that it is the body showing an immune response.
Hope this helps,
karen
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- August 2, 2011 at 2:16 am
Thanks, Karen and Michael.
Michael, I do not know what his ALC is. I am trying to find out. He did get the white beard, though.
Regarding whether diarrhea is indicative of a response, I think I meant colitis rather than diarrhea, including getting colitis rather quickly.
Thank you for your information and links, which I am still going through and digesting.
One other question: he apparently had a minor fainting episode today — basically felt nauseous and felt faint but did not lose consciousness. About a month ago he did kind of lose consciousness also, perhaps not all the way. He is speaking with his doctor about this, of course. Could this be simply a reaction from the dacarbazine/ipi, or could it be an indication of brain mets? He has no other such symptoms (loss of memory or alertness, etc.). And the brain scan in April was clean.
Thanks again for the helpful responses. I really appreciate it.
Ray
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- August 2, 2011 at 2:16 am
Thanks, Karen and Michael.
Michael, I do not know what his ALC is. I am trying to find out. He did get the white beard, though.
Regarding whether diarrhea is indicative of a response, I think I meant colitis rather than diarrhea, including getting colitis rather quickly.
Thank you for your information and links, which I am still going through and digesting.
One other question: he apparently had a minor fainting episode today — basically felt nauseous and felt faint but did not lose consciousness. About a month ago he did kind of lose consciousness also, perhaps not all the way. He is speaking with his doctor about this, of course. Could this be simply a reaction from the dacarbazine/ipi, or could it be an indication of brain mets? He has no other such symptoms (loss of memory or alertness, etc.). And the brain scan in April was clean.
Thanks again for the helpful responses. I really appreciate it.
Ray
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- August 2, 2011 at 2:10 pm
I am not a doctor, so I do not feel I am one to answer that question in your fathers case. I do recall that both dacarbazine and Yervoy have forgetfulness, fainting, dizzyness etc. listed as a side effect.
When is his next brain scan? You mention MRI and bone scan in your last post. Was his last brain scan a MRI? You may wish to ask for another to rule it out. The last one can be used as a baeline.
Good luck,
Michael
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- August 2, 2011 at 2:10 pm
I am not a doctor, so I do not feel I am one to answer that question in your fathers case. I do recall that both dacarbazine and Yervoy have forgetfulness, fainting, dizzyness etc. listed as a side effect.
When is his next brain scan? You mention MRI and bone scan in your last post. Was his last brain scan a MRI? You may wish to ask for another to rule it out. The last one can be used as a baeline.
Good luck,
Michael
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- August 1, 2011 at 10:07 pm
I can't go based on experience, but I can tell you what I have read online and here.
To try and answer your questions:
#1 The diarrhea is the #1 side effect of Yervoy, so it does not mean that to have it is indicative of a response.
#2 From what I have read, a steroid (prednisone) does not affect yervoy, but should still be tapered if/when things are more manageable.
#3 Not really sure I can answer as everyone is different.
Also, do you know if your fathers ALC (absolute Lymphocyte Count) increased? From what I have read, if the level is over 1,000 by the second dose of ipilimumab, there is a >5% chance of response and they may be considered a responder. Also, some side effects that I have heard of on the board that do indicate a response are white hair, facial hair or beard.
Read on:
Published Online: 8 Feb 2010 Copyright © 2010 American Cancer Society
Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting.
lymphocyte count after 2 doses correlates with survival
Results: A total of 53 patients were enrolled, with 51 evaluable. Grade 3/4 immune-related adverse events were noted in 29% of patients, with the most common immune-related adverse events being pruritus (43%), rash (37%), and diarrhea (33%). On the basis of immune-related response criteria, the response rate (CR + PR) was 12% (95% confidence interval [CI], 5%-25%), whereas 29% had SD (95% CI, 18%-44%). The median progression-free survival was 2.6 months (95% CI, 2.3-5.2 months), whereas the median overall survival (OS) was 7.2 months (95% CI, 4.0-13.3 months). Patients with an absolute lymphocyte count (ALC) 1000/L after 2 ipilimumab treatments (Week 7) had a significantly improved clinical benefit rate (51% vs 0%; P = .01) and median OS (11.9 vs 1.4 months; P < .001) compared with those with an ALC <1000/l
Conclusion: The results confirm that ipilimumab is clinically active in patients with advanced refractory melanoma. The ALC after 2 ipilimumab treatments appears to correlate with clinical benefit and OS, and should be prospectively validated.
I have also read on other sites that side effects occur in up to 84% of patients and the most common side effects of ipilimumab occur in the gastrointestinal tract (such as diarrhea and inflammation of the colon) and the skin (such as rash and inflammation of the skin). Less frequently occurring side effects include hepatitis, inflammation of the pituitary gland (hypophysitis), eye inflammation (uveitis), and kidney problems (nephritis).
Here is a link to a study which shows the response rate and side effects:
From: http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(09)70334-1/abstract
February, 2010.
Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomized, double-blind, multicentre, phase 2, dose-ranging study.
Findings:
The best overall response rate was 11·1% for 10 mg/kg, 4·2% for 3 mg/kg, and 0% for 0·3 mg/kg. Immune-related adverse events of any grade arose in 50 of 71, 46 of 71, and 19 of 72 patients at doses of 10 mg/kg, 3 mg/kg, and 0·3 mg/kg, respectively; the most common grade 3—4 adverse events were gastrointestinal immune-related events (11 in the 10 mg/kg group, two in the 3 mg/kg group, none in the 0·3 mg/kg group) and diarrhea (ten in the 10 mg/kg group, one in the 3 mg/kg group, none in the 0·3 mg/kg group).
In another study:
http://knol.google.com/k/krishan-maggon/ipilimumab-bms-review-a-cancer/3fy5eowy8suq3/107#
In a Phase II trial in 155 patients with pretreated stage III or stage IV melanoma, the best overall response rate (modified WHO criteria) was 5.8% short of 10% minimum required by FDA. The disease was controlled in 27% of patients treated with 10 mg/kg induction (4 cycles) and maintenance doses. The survival at 1 year was 47% and at 2 year 33%. Forty three patients had progressive disease. Adverse drug reactions were immune related, 19% patients had Grade 3 and 3.2% Grade 4 dermatological and gastrointestinal toxicity. In a compassionate use trial in MSKC in advanced refractory patients, 53 patients were enrolled and 51 were eligible for analysis. grade 3 toxicity was reported by 29% of patients, 12% of patients had tumor response (CR+PR) and 29% had stable disease. Overall survival in this group was 7.2 months and progression free survival was 2.6 months.
Best wishes,
Michael
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