> Could you please tell me what was unsatisfactory about the response you
> received from Barlogie here:
I have attached my original concern and Dr Barlogie's reply. With careful reading and analysis, one can easily see the unanswered or incompletely addressed questions. This applies to some extent or the other to all questions I have raised about MIRT work in journals.
However, the JCO response from Dr Barlogie (your link) was the first time the magnitude of "unknown" deaths became obvious to me. What I had suspected to be deaths due to toxicity not being revealed explicitly suddenly turned into inadequate monitoring of clinical trials and/or possible attempts at hiding toxicity/relapse - bringing up the question of reliability of all the data. When I looked at other reports, a consistent theme emerged - giving rise to the analysis I wrote (largely for my own satisfaction) - which gave rise to this discussion thread.
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Report on Myeloma Trials at UAMS / Arkansas
- Attachments
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e125.full.pdf- Barlogie reply JCO
- (94.47 KiB) Downloaded 122 times
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- e124.full.pdf
- Mehta letter JCO
- (44.44 KiB) Downloaded 98 times
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jmehta - Name: Jayesh Mehta MD
Re: Report on Myeloma Trials at UAMS / Arkansas
Hi Dr. Mehta,
You write in JCO:
"Figure 2D shows that 159 patients have died after experiencing disease progression. This
suggests that 128 of 668 patients (19%) died as a result of nonrelapse causes. If true, this indicates that the treatment approach is prohibitively toxic. If the 19% estimate that I derived on the basis of available data is incorrect, the entire analysis and data set need to be revisited for possible inaccuracies, not only for this article but for all publications pertaining to the Total Therapy 2 trial."
I agree, this is indicative of prohibitively toxic therapeutic regimen and have stated so regarding patients survival being a high risk on TT1-3.
and you reply:
"What I had suspected to be deaths due to toxicity not being revealed explicitly suddenly turned into inadequate monitoring of clinical trials and/or possible attempts at hiding toxicity/relapse - bringing up the question of reliability of all the data"
Actually, the inadequate monitoring, or consistent pattern of how deaths are categorized is specific to TT1-3 trials.
Or are you raising the even larger question of how deaths are reported in ALL myeloma trials not just those at MIRT?
If so, the question remains, what was unsatisfactory about Dr. Barlogie's reply in JCO, which I posted the link to and you provided a pdf to?
What do you believe was unanswered, the reply, seems to be quite thorough...despite indicating that they have excluded those patients who they are categorizing as 'high-risk' which certainly is convenient.
You write in JCO:
"Figure 2D shows that 159 patients have died after experiencing disease progression. This
suggests that 128 of 668 patients (19%) died as a result of nonrelapse causes. If true, this indicates that the treatment approach is prohibitively toxic. If the 19% estimate that I derived on the basis of available data is incorrect, the entire analysis and data set need to be revisited for possible inaccuracies, not only for this article but for all publications pertaining to the Total Therapy 2 trial."
I agree, this is indicative of prohibitively toxic therapeutic regimen and have stated so regarding patients survival being a high risk on TT1-3.
and you reply:
"What I had suspected to be deaths due to toxicity not being revealed explicitly suddenly turned into inadequate monitoring of clinical trials and/or possible attempts at hiding toxicity/relapse - bringing up the question of reliability of all the data"
Actually, the inadequate monitoring, or consistent pattern of how deaths are categorized is specific to TT1-3 trials.
Or are you raising the even larger question of how deaths are reported in ALL myeloma trials not just those at MIRT?
If so, the question remains, what was unsatisfactory about Dr. Barlogie's reply in JCO, which I posted the link to and you provided a pdf to?
What do you believe was unanswered, the reply, seems to be quite thorough...despite indicating that they have excluded those patients who they are categorizing as 'high-risk' which certainly is convenient.
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Report on Myeloma Trials at UAMS / Arkansas
"Or are you raising the even larger question of how deaths are reported in ALL myeloma trials not just those at MIRT?"
That is an excellent question.
That is an excellent question.
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stann
Re: Report on Myeloma Trials at UAMS / Arkansas
Dr. Mehta and suzierose,
It is actually very helpful that you were kind enough to post the JCO articles so we can all review them without others' filters.
To me the bottom line is that after 12 years 54.6% (365/668) of MIRT's patients are alive, that only 7.6% (89/668) of patients die from the treatments and that the treatment-related dealths almost all occur within the first year. It levels out after that.
Perhaps most importantly, only 24.4% (163/668) of MIRT patients die of their disease in 12 years which seems to occur across time but appears to almost level off after about 10 years. Are the those around after 12 years going to be cured if they too pass away, hopefully after 20 years, from natural causes?
The 13.3% of unknown deaths isn't that surprising to me because these are longterm studies where patients may have been treated, recovered, moved, had to change insurance, employers or the other life experiences we all have and are lost to followup. Does unknown actually mean natural dealths like cardiovascular disease and other deaths. Are these patients cured because they died of something other than myeloma.
I know of no other studies that even come close to this longevity- you really cannot compare unknown dealths from a study lasting 2 years (typical of reported myeloma studies) with one lasting 12 years.
A more optimistic reading of these numbers is that 13.3% of patients passed away of natural causes (neither myeloma relapse nor treatment-related) which seems feasible for an older population and that 54.6% are still alive after 12 years which to me is truly incredible.
Add to this that TT1-2 were before this incredible era of targeted therapies (proteosome inhibitors, immune modulators and gene expression analysis) and the future is very bright for us myeloma patients.
I agree that total therapy is not for everyone and I do not recommend them but as Dr. Mehta says the concept is valid and generally accepted by the myeloma community.
suzierose may be right that in the future that these aggressive treatments will hopefully be replaced with less toxic "smart" treatments designed based on each person's disease. I don't know if we are there yet, but I think it is inevitable that we will get there soon- maybe in the next 3-4 years.
All of us that are alive today should be grateful to those who went before us. I've know survivor's quilt because all those friends and fellow patients who were with me at the beginning have passed now but we all stand upon their shoulders as we fight the good fight.
All my best to everyone for a wonderful holiday season,
Dan
It is actually very helpful that you were kind enough to post the JCO articles so we can all review them without others' filters.
To me the bottom line is that after 12 years 54.6% (365/668) of MIRT's patients are alive, that only 7.6% (89/668) of patients die from the treatments and that the treatment-related dealths almost all occur within the first year. It levels out after that.
Perhaps most importantly, only 24.4% (163/668) of MIRT patients die of their disease in 12 years which seems to occur across time but appears to almost level off after about 10 years. Are the those around after 12 years going to be cured if they too pass away, hopefully after 20 years, from natural causes?
The 13.3% of unknown deaths isn't that surprising to me because these are longterm studies where patients may have been treated, recovered, moved, had to change insurance, employers or the other life experiences we all have and are lost to followup. Does unknown actually mean natural dealths like cardiovascular disease and other deaths. Are these patients cured because they died of something other than myeloma.
I know of no other studies that even come close to this longevity- you really cannot compare unknown dealths from a study lasting 2 years (typical of reported myeloma studies) with one lasting 12 years.
A more optimistic reading of these numbers is that 13.3% of patients passed away of natural causes (neither myeloma relapse nor treatment-related) which seems feasible for an older population and that 54.6% are still alive after 12 years which to me is truly incredible.
Add to this that TT1-2 were before this incredible era of targeted therapies (proteosome inhibitors, immune modulators and gene expression analysis) and the future is very bright for us myeloma patients.
I agree that total therapy is not for everyone and I do not recommend them but as Dr. Mehta says the concept is valid and generally accepted by the myeloma community.
suzierose may be right that in the future that these aggressive treatments will hopefully be replaced with less toxic "smart" treatments designed based on each person's disease. I don't know if we are there yet, but I think it is inevitable that we will get there soon- maybe in the next 3-4 years.
All of us that are alive today should be grateful to those who went before us. I've know survivor's quilt because all those friends and fellow patients who were with me at the beginning have passed now but we all stand upon their shoulders as we fight the good fight.
All my best to everyone for a wonderful holiday season,
Dan
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Dan in Phoenix
Re: Report on Myeloma Trials at UAMS / Arkansas
Stann & Susie
I would like to add a simple note. As a former UAMS/ACRC patient I can speak from experience. Yes, the treatments are quite challenging and intense. I am a 17 year tandem transplant survivor. I feel that I owe my life and survivorship to doing what I thought was right for ME. Each patient has different needs. Having said that, it is a very personal decision where to go or who should treat us as individual human beings who happen to have multiple myeloma. I was under no illusions that the treament they would give me would be anything other thatn VERY aggressive. I don;t particularly care for multiple myeloma so aggressive is exactly what I wanted.
I am on mainenance therapy and have since had a third transplant. My choice, plain and simple. I am also alive and living a wonderful life. As a survivor, I beg anyone who posts here, please dont use this forum to rant and criticize the dedicated work of those trying to beat this dragon into submission. I dont care if they make a profit if it helps the research that keeps us alive. I suspect that many other multiple myeloma survivors dont either. I am blessed to still be here and am more that grateful that I had the opportunity to go to UAMS/ACRC.
I truly enjoy coming to this forum and reading of the many informative posts, reserach and motivation to fight back against this dragon. What we need most is facts and hope. HOpe that someday people will say "multiple what" because it is long been defeated. Thank you to everyone who makes that possible.
I would like to add a simple note. As a former UAMS/ACRC patient I can speak from experience. Yes, the treatments are quite challenging and intense. I am a 17 year tandem transplant survivor. I feel that I owe my life and survivorship to doing what I thought was right for ME. Each patient has different needs. Having said that, it is a very personal decision where to go or who should treat us as individual human beings who happen to have multiple myeloma. I was under no illusions that the treament they would give me would be anything other thatn VERY aggressive. I don;t particularly care for multiple myeloma so aggressive is exactly what I wanted.
I am on mainenance therapy and have since had a third transplant. My choice, plain and simple. I am also alive and living a wonderful life. As a survivor, I beg anyone who posts here, please dont use this forum to rant and criticize the dedicated work of those trying to beat this dragon into submission. I dont care if they make a profit if it helps the research that keeps us alive. I suspect that many other multiple myeloma survivors dont either. I am blessed to still be here and am more that grateful that I had the opportunity to go to UAMS/ACRC.
I truly enjoy coming to this forum and reading of the many informative posts, reserach and motivation to fight back against this dragon. What we need most is facts and hope. HOpe that someday people will say "multiple what" because it is long been defeated. Thank you to everyone who makes that possible.
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Marcie
Re: Report on Myeloma Trials at UAMS / Arkansas
Hi Marcie,
Wow. 17 years? You are a pioneer! I have traveled the very aggressive route too and have no regrets. Quality of life is excellent too. And I thank people such as yourself as well as UAMS for blazing the trail.
My last post to Suzie was only that I also wondered if Dr. Mehta thought the entire multiple myeloma world was under reporting deaths due to treatment. Or if he thought it was limited to UAMS.
Even though Dr. Mehta is challenging UAMS reporting of certain aspects of their trials, he also states this on this thread.
"I am a firm believer in the utility of high-dose therapy and autotransplantation – including tandem transplantation in appropriate patients"
I find that statement by Dr. Mehta to be very telling.
I too, also hope all involved in myeloma research, including the chemical companies make lots and lots of money. (I sure hope our new health care situation does not hinder future research).
Here's to another 17 years! Stann
Wow. 17 years? You are a pioneer! I have traveled the very aggressive route too and have no regrets. Quality of life is excellent too. And I thank people such as yourself as well as UAMS for blazing the trail.
My last post to Suzie was only that I also wondered if Dr. Mehta thought the entire multiple myeloma world was under reporting deaths due to treatment. Or if he thought it was limited to UAMS.
Even though Dr. Mehta is challenging UAMS reporting of certain aspects of their trials, he also states this on this thread.
"I am a firm believer in the utility of high-dose therapy and autotransplantation – including tandem transplantation in appropriate patients"
I find that statement by Dr. Mehta to be very telling.
I too, also hope all involved in myeloma research, including the chemical companies make lots and lots of money. (I sure hope our new health care situation does not hinder future research).
Here's to another 17 years! Stann
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Stann - Name: Stann
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: 9/11/09
- Age at diagnosis: 46
Re: Report on Myeloma Trials at UAMS / Arkansas
Hi everyone,
Great discussion. I did want to point out a couple of things. Links to the articles Dr. Mehta just posted were posted on the FIRST PAGE of the thread. It is obvious that people were posting things without reading the links. I always post links when I put quotes or statistics up so everyone can read the entire paper and make their own judgement about the paper. I posted 2 links that Dr. Barlogie was the author of and he posted on Page 3. I have no idea what Dan was referring to when he wrote:
"It is actually very helpful that you were kind enough to post the JCO articles so we can all review them without others' filters."
Those links have been in the thread from the beginning.
IMO research should be done and presented so patients can make an informed choice on what therapy is best for them. If you read Nicks first post in the thread he makes this comment:
"The last domino to fall is tandem transplants, and I suspect that Bart will once again be proven right."
I do not think research should be done to prove you are right. That is how we end up with a research paper that shows graphs of outcomes for patients that does not include 19% (about one fifth) of the patients in the trial.
I know all patients are not going to do what I did, but I put together a cost/benefit (risk/reward, opportunity costs) analysis of all the potential treatments available in late 2010 (when I was diagnosed) and decided a myeloablative allo was the best therapy for me. The only way to do a detailed analysis like that is to have reliable data when doing the analysis.
We are now over 5,100 views on this thread and 115 replies. I hope it has been as informative to everyone else as it has been for me.
Mark
Great discussion. I did want to point out a couple of things. Links to the articles Dr. Mehta just posted were posted on the FIRST PAGE of the thread. It is obvious that people were posting things without reading the links. I always post links when I put quotes or statistics up so everyone can read the entire paper and make their own judgement about the paper. I posted 2 links that Dr. Barlogie was the author of and he posted on Page 3. I have no idea what Dan was referring to when he wrote:
"It is actually very helpful that you were kind enough to post the JCO articles so we can all review them without others' filters."
Those links have been in the thread from the beginning.
IMO research should be done and presented so patients can make an informed choice on what therapy is best for them. If you read Nicks first post in the thread he makes this comment:
"The last domino to fall is tandem transplants, and I suspect that Bart will once again be proven right."
I do not think research should be done to prove you are right. That is how we end up with a research paper that shows graphs of outcomes for patients that does not include 19% (about one fifth) of the patients in the trial.
I know all patients are not going to do what I did, but I put together a cost/benefit (risk/reward, opportunity costs) analysis of all the potential treatments available in late 2010 (when I was diagnosed) and decided a myeloablative allo was the best therapy for me. The only way to do a detailed analysis like that is to have reliable data when doing the analysis.
We are now over 5,100 views on this thread and 115 replies. I hope it has been as informative to everyone else as it has been for me.
Mark
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Mark
Re: Report on Myeloma Trials at UAMS / Arkansas
I am an immunologist with more than 40 years teaching and research at medical schools. I have created animal myelomas, made numerous monoclonals and have many patents (plus 150 per-reviewed publications). I am not impressed with lay criticisms or infact uninformed physician "letters" that have not gone through any type of professional scrutiny. I can talk the talk and walk the walk because I am currently in a TT protocol created and administered by Dr. Barlogie and UAMS. After two tandems and almost 3 years of maintenance at the UAMS clinic. I have read the literature, studied the results and have talked to literally hundreds of patients at the clinic. This is the way one learns about the patient pools and new patients from other centers (names shall go unmentioned) where oncologists have sent patients to UAMS as "last resort" attempts at stabilization where extension of life is the only possibility {i.e. cure is beyond concept). Many of these folks are still alive after 3 years.
Let me tell you that Drs. Nair and Barlogie have saved my life. Indeed I presented as a patient from a surgery where I was told I had 3- 6 months. Who in this audience has had such an experience? Yes I was low risk, in my upper 60s and in otherwise excellent health (an active runner for 50 years, no diabetes or cardiovascular events, etc.). I have committed myself to diligent adherence to my maintenance protocol. It is indeed rigorous but I still work full-time. I pay attention. If one doesn't infectious disease will surely follow. Everything is connected folks. I am completely convinced that UAMS is the only place in the world where one is not only given a chance for survival but long term prospects for relatively good health are clearly possible. With this knowledge, why would anybody go any where else?
Let me tell you that Drs. Nair and Barlogie have saved my life. Indeed I presented as a patient from a surgery where I was told I had 3- 6 months. Who in this audience has had such an experience? Yes I was low risk, in my upper 60s and in otherwise excellent health (an active runner for 50 years, no diabetes or cardiovascular events, etc.). I have committed myself to diligent adherence to my maintenance protocol. It is indeed rigorous but I still work full-time. I pay attention. If one doesn't infectious disease will surely follow. Everything is connected folks. I am completely convinced that UAMS is the only place in the world where one is not only given a chance for survival but long term prospects for relatively good health are clearly possible. With this knowledge, why would anybody go any where else?
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