With all due respect, and I never miss reading your posts Nick, when you wrote:
PLENTY of centers now pursue more aggressive therapy than they did a few years ago, in part as a result of Bart’s success. Huntsman is MORE aggressive than UAMS given they use bendamustine in addition to melphalan for high dose ACST. Michigan does tandem transplants. Now that Tricot is at Iowa, they will be aggressive.
Maybe you are right, but I know of others, including myself that will not go to IA now to be treated even though it is closer because of Tricot.
How does UAMS chart "Scoop on Dan's' death? Do they leave him out since he left the program?
If UAMS could respond that would be a great insight into their reporting protocol. Just because they are too aggressive for me, doesn't mean I don't want them to be able to set all of the facts straight about their work.
Forums
Re: Report on Myeloma Trials at UAMS
It appears that Nick has carte blanche posting to extoll the director of MiRT and that opposing views are being moderated from one poster only...hmmmm
In the 2008 campaign the Presidential candidate was described as a maverick. When a physician is described as a maverick it is defamatory.
In the 2008 campaign the Presidential candidate was described as a maverick. When a physician is described as a maverick it is defamatory.
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Report on Myeloma Trials at UAMS
I have been involved, as a caregiver, with the TT-3 protocol so I have some firsthand exposure to the protocols in Little Rock. I would like to comment, from my viewpoint, on several of the issues raised in this forum. Please note that these are just my subjective opinions based on my experience, nothing more.
First, on the concept of MIRT’s TT being a money pit. MIRT’s basic philosophy is that everything – induction cycles, transplants, and consolidation cycles - are performed as out-patient procedures. This not only greatly reduces the potential for hospital related infections but significantly reduces the cost of treatment. Also, although I have not seen their new offices, the waiting rooms and doctor/patient meeting rooms could be viewed as very utilitarian and far from what one would expect in a money pit operation. In fact, I was always stuck by how small and unassuming Dr Barlogie’s office was. And, it was my perception that salaries were far from the top end of the medical spectrum. Yes, there are a lot of tests, but remember, MIRT is a “Research” organization. In total, my own opinion is that the idea of MIRT being a money pit is preposterous.
On the subject of blind studies, it was my firm belief that Dr Barlogie would not blindly follow the protocol if he truly believed that deviation was in the best interest of the patient. So patients receive what MIRT believes to the best treatment based on the individual's situation regardless of the “protocol”. My own personal belief was that BB followed protocols rather than performed blind studies because he was unwilling to subject half of his patients to less than what he considered to have the best chance of success. This may not be the most elegant, rigorous. scientific, statistical approach to proving something but it is a much more humane, patient-friendly approach.
And it has all of a sudden occurred to me to wonder, if one side of a blind study was a total treatment approach, what sort of treatment would the other side receive -- no treatment? one novel drug ? two novel drugs? one chemo cycle? no transplants? one transplant? How could a meaningful blind study that everyone would agree on ever be defined? I know, the medical profession could devise some sort of comparison but wouldn’t we always question the validity of such a comparison if it differed from the treatment we individually receive?
And, one final comment about side effects. It was always my personal observation that the side effects associated with total therapy were not significantly worse, in aggregate, than those associated with the more conventional, less aggressive treatments.
First, on the concept of MIRT’s TT being a money pit. MIRT’s basic philosophy is that everything – induction cycles, transplants, and consolidation cycles - are performed as out-patient procedures. This not only greatly reduces the potential for hospital related infections but significantly reduces the cost of treatment. Also, although I have not seen their new offices, the waiting rooms and doctor/patient meeting rooms could be viewed as very utilitarian and far from what one would expect in a money pit operation. In fact, I was always stuck by how small and unassuming Dr Barlogie’s office was. And, it was my perception that salaries were far from the top end of the medical spectrum. Yes, there are a lot of tests, but remember, MIRT is a “Research” organization. In total, my own opinion is that the idea of MIRT being a money pit is preposterous.
On the subject of blind studies, it was my firm belief that Dr Barlogie would not blindly follow the protocol if he truly believed that deviation was in the best interest of the patient. So patients receive what MIRT believes to the best treatment based on the individual's situation regardless of the “protocol”. My own personal belief was that BB followed protocols rather than performed blind studies because he was unwilling to subject half of his patients to less than what he considered to have the best chance of success. This may not be the most elegant, rigorous. scientific, statistical approach to proving something but it is a much more humane, patient-friendly approach.
And it has all of a sudden occurred to me to wonder, if one side of a blind study was a total treatment approach, what sort of treatment would the other side receive -- no treatment? one novel drug ? two novel drugs? one chemo cycle? no transplants? one transplant? How could a meaningful blind study that everyone would agree on ever be defined? I know, the medical profession could devise some sort of comparison but wouldn’t we always question the validity of such a comparison if it differed from the treatment we individually receive?
And, one final comment about side effects. It was always my personal observation that the side effects associated with total therapy were not significantly worse, in aggregate, than those associated with the more conventional, less aggressive treatments.
Re: Report on Myeloma Trials at UAMS
Can't find the use of the word money pitt in the thread.
There appears to be some fuzziness about 'blinded' trials vs. randomized controlled trials.
A randomized controlled trial (RCT) (or randomized comparative trial) is a specific type of scientific experiment, and the preferred design for a clinical trial. RCT are often used to test the efficacy of various types of intervention within a patient population. RCT may also provide an opportunity to gather useful information about adverse effects, such as drug reactions.
The terms "RCT" and randomized trial are often used synonymously, but some authors distinguish between "RCTs" which compare treatment groups with control groups not receiving treatment (as in a placebo-controlled study), and "randomized trials" which can compare multiple treatment groups with each other
In terms of the comparator trials though, what would have happened is that we would have had randomized trials of effective therapies. Not one arm is a loser and the other could be highly effective. Rather it would have been an older effective therapy (such as alklylators/dex) vs a newer "effective" therapy such as VAD TT1-2 followed by tandem SCT. Comparative induction effective therapies. Those would not be hard choices. It would be unethical to design a trial for multiple myeloma therapy at this juncture which was not challenging efficacy vs. more efficacy. Who is the best NYGiants or NEPatriots? Which one wins. Both teams are great..now let's have the SuperBowl and determine the champions.
The only trial comparisons out there are between TT1 vs. TT2 vs. TT3..nicely convenient for Barlogie.
Why aren't there head to head comparator trials of any of the T1-3 trials with any other multiple myeloma therapy that has been shown to be effective? Randomization into such trials would not be allowing a computer choice. Rather, the patient is doing precisely what we do presently which is electing a proven clinically effective therapy. However, the outcome would show us which therapy demonstrates the greatest efficacy. VD-Pace is most toxic stuff on the market and like throwing the kitchen sink at multiple myeloma. We already know it is highly toxic, the question is it highly effective over and beyond other EFFECTIVE drug regimens for multiple myeloma.
Conventional therapy for myeloma is not high-dose chemotherapy. High-dose chemotherapy does have significantly worse side effects. Many of which have dose limiting toxicity due to lungs and GI adverse events particularly when multiple toxic drugs are used in combination.Point of fact, the toxicity is so great it necessitates salvage stem cells for the patients survival from the high-dose chemotherapy.
Are there regimens being used that are not high-dose chemotherapy in TT1-3?
There appears to be some fuzziness about 'blinded' trials vs. randomized controlled trials.
A randomized controlled trial (RCT) (or randomized comparative trial) is a specific type of scientific experiment, and the preferred design for a clinical trial. RCT are often used to test the efficacy of various types of intervention within a patient population. RCT may also provide an opportunity to gather useful information about adverse effects, such as drug reactions.
The terms "RCT" and randomized trial are often used synonymously, but some authors distinguish between "RCTs" which compare treatment groups with control groups not receiving treatment (as in a placebo-controlled study), and "randomized trials" which can compare multiple treatment groups with each other
In terms of the comparator trials though, what would have happened is that we would have had randomized trials of effective therapies. Not one arm is a loser and the other could be highly effective. Rather it would have been an older effective therapy (such as alklylators/dex) vs a newer "effective" therapy such as VAD TT1-2 followed by tandem SCT. Comparative induction effective therapies. Those would not be hard choices. It would be unethical to design a trial for multiple myeloma therapy at this juncture which was not challenging efficacy vs. more efficacy. Who is the best NYGiants or NEPatriots? Which one wins. Both teams are great..now let's have the SuperBowl and determine the champions.
The only trial comparisons out there are between TT1 vs. TT2 vs. TT3..nicely convenient for Barlogie.
Why aren't there head to head comparator trials of any of the T1-3 trials with any other multiple myeloma therapy that has been shown to be effective? Randomization into such trials would not be allowing a computer choice. Rather, the patient is doing precisely what we do presently which is electing a proven clinically effective therapy. However, the outcome would show us which therapy demonstrates the greatest efficacy. VD-Pace is most toxic stuff on the market and like throwing the kitchen sink at multiple myeloma. We already know it is highly toxic, the question is it highly effective over and beyond other EFFECTIVE drug regimens for multiple myeloma.
Conventional therapy for myeloma is not high-dose chemotherapy. High-dose chemotherapy does have significantly worse side effects. Many of which have dose limiting toxicity due to lungs and GI adverse events particularly when multiple toxic drugs are used in combination.Point of fact, the toxicity is so great it necessitates salvage stem cells for the patients survival from the high-dose chemotherapy.
Are there regimens being used that are not high-dose chemotherapy in TT1-3?
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Myeloma Trials at UAMS - Many questions but few answers
While acknowledging the important contributions made by several individuals from the Arkansas program over the years, there are questions about published and presented data from Arkansas that need to be addressed openly and in depth. The post from Drs Barlogie and Crowley does not do that.
The point of concern is not one of deaths from natural causes unrelated to myeloma or complications of therapy. It is the number and proportion of deaths “unknown” or “other” causes. A large proportion of deaths from “unknown” causes suggests inadequacy of follow-up, supervision, and/or attempts to find out the real cause of death, and/or incorrect assignment of the cause of death. As an example of the latter, a death from stroke occurring in a relatively young patient with no history of cerebrovascular disease while on treatment is highly likely to be related to therapy than to a natural stroke. Classifying this as a death from an unrelated cause is, at the very least, inappropriate.
The other myeloma and non-myeloma trial examples are provided to illustrate what the proportions of unclear data ought to be in careful studies. Interestingly, most of these are multi-center studies where the amount of missing data is expected to be more than single-center studies such as those from Arkansas. Yet, the reverse is the case.
The argument that “normal mortality” deaths are related to longer follow-up on Total Therapy studies is not supported by the data that have been presented. An examination of the curve provided by MIRT in their response to my letter in the Journal of Clinical Oncology (http://www.jco.ascopubs.org/content/29/5/e125/F1.large.jpg) shows that “unknown” deaths have been seen quite early – starting a few months into therapy. Indeed, the curve suggests that at least 20-25 deaths have occurred within 3 years of starting therapy.
It is essential to know the time to death from study initiation for the 89 patients dying of unknown causes, their ages at enrollment and death, and their status (disease, type of therapy being given, general condition, organ function) at the last follow-up before death and at the time of death. This minimum information would need to be augmented by a careful review of the attempts made to find the cause of death by MIRT and the local physician’s assessment of the death in order to find out whether the causes are truly unknown/unrelated or not. This review ought to be carried out by truly independent individuals interested in myeloma and patient welfare – not consultants hired by MIRT.
I doubt that the solo FDA inspector – whose report should be made available in full to the myeloma community (physicians and patients) – had either the intellectual (medical knowledge) or the physical (time) resources to study this carefully – especially looking at nuances of causes of death.
I have heard from one of the Data Safety Monitoring Board members that they looked only at survival and not at causes of death. Were Dr Weiss and his team aware of the number of deaths from “unknown” causes? I believe it is critical for the myeloma community to have access to all of Dr Weiss’ reports as well.
The malady is not confined to TT studies. A study from Arkansas on the use of thalidomide in smoldering myeloma (UARK 98-036, NCT00083382) provided no information on age of patients – and also omitted some crucial details related to deaths of study subjects. 10 of 76 died of “unrelated causes." The unrelated causes were not specified. No information was provided on how many of the unrelated deaths occurred while patients were actually receiving thalidomide. No information was provided on when these deaths occurred in relation to starting/stopping thalidomide. Ages of the patients dying of unrelated causes were not provided. There was no information on the age of patients dying of unknown causes compared with the whole group. A letter published in Blood asking these questions (clearly relevant to patient welfare) went unreplied.
This is a critically important issue that is black-and-white for me: either there is something that is being hidden by keeping information from people who can dissect it carefully, completely and thoroughly - or there isn’t. If it is the latter, the Arkansas group needs to make the data available for independent scrutiny.
These questions should have been asked during the peer-review process by the reviewers – and by editors of journals that published the papers. Unfortunately, they were not. Quis custodiet ipsos custodes? I thank the Myeloma Beacon for providing a forum to ask questions that can only help the myeloma community by keeping a watch on the watchmen.
Jayesh Mehta MD
Professor of Medicine
Director, Hematopoietic Stem Cell Transplantation Program
The Robert H Lurie Comprehensive Cancer Center
Northwestern University Feinberg School of Medicine
Chicago
The point of concern is not one of deaths from natural causes unrelated to myeloma or complications of therapy. It is the number and proportion of deaths “unknown” or “other” causes. A large proportion of deaths from “unknown” causes suggests inadequacy of follow-up, supervision, and/or attempts to find out the real cause of death, and/or incorrect assignment of the cause of death. As an example of the latter, a death from stroke occurring in a relatively young patient with no history of cerebrovascular disease while on treatment is highly likely to be related to therapy than to a natural stroke. Classifying this as a death from an unrelated cause is, at the very least, inappropriate.
The other myeloma and non-myeloma trial examples are provided to illustrate what the proportions of unclear data ought to be in careful studies. Interestingly, most of these are multi-center studies where the amount of missing data is expected to be more than single-center studies such as those from Arkansas. Yet, the reverse is the case.
The argument that “normal mortality” deaths are related to longer follow-up on Total Therapy studies is not supported by the data that have been presented. An examination of the curve provided by MIRT in their response to my letter in the Journal of Clinical Oncology (http://www.jco.ascopubs.org/content/29/5/e125/F1.large.jpg) shows that “unknown” deaths have been seen quite early – starting a few months into therapy. Indeed, the curve suggests that at least 20-25 deaths have occurred within 3 years of starting therapy.
It is essential to know the time to death from study initiation for the 89 patients dying of unknown causes, their ages at enrollment and death, and their status (disease, type of therapy being given, general condition, organ function) at the last follow-up before death and at the time of death. This minimum information would need to be augmented by a careful review of the attempts made to find the cause of death by MIRT and the local physician’s assessment of the death in order to find out whether the causes are truly unknown/unrelated or not. This review ought to be carried out by truly independent individuals interested in myeloma and patient welfare – not consultants hired by MIRT.
I doubt that the solo FDA inspector – whose report should be made available in full to the myeloma community (physicians and patients) – had either the intellectual (medical knowledge) or the physical (time) resources to study this carefully – especially looking at nuances of causes of death.
I have heard from one of the Data Safety Monitoring Board members that they looked only at survival and not at causes of death. Were Dr Weiss and his team aware of the number of deaths from “unknown” causes? I believe it is critical for the myeloma community to have access to all of Dr Weiss’ reports as well.
The malady is not confined to TT studies. A study from Arkansas on the use of thalidomide in smoldering myeloma (UARK 98-036, NCT00083382) provided no information on age of patients – and also omitted some crucial details related to deaths of study subjects. 10 of 76 died of “unrelated causes." The unrelated causes were not specified. No information was provided on how many of the unrelated deaths occurred while patients were actually receiving thalidomide. No information was provided on when these deaths occurred in relation to starting/stopping thalidomide. Ages of the patients dying of unrelated causes were not provided. There was no information on the age of patients dying of unknown causes compared with the whole group. A letter published in Blood asking these questions (clearly relevant to patient welfare) went unreplied.
This is a critically important issue that is black-and-white for me: either there is something that is being hidden by keeping information from people who can dissect it carefully, completely and thoroughly - or there isn’t. If it is the latter, the Arkansas group needs to make the data available for independent scrutiny.
These questions should have been asked during the peer-review process by the reviewers – and by editors of journals that published the papers. Unfortunately, they were not. Quis custodiet ipsos custodes? I thank the Myeloma Beacon for providing a forum to ask questions that can only help the myeloma community by keeping a watch on the watchmen.
Jayesh Mehta MD
Professor of Medicine
Director, Hematopoietic Stem Cell Transplantation Program
The Robert H Lurie Comprehensive Cancer Center
Northwestern University Feinberg School of Medicine
Chicago
Last edited by jmehta on Sat Oct 06, 2012 1:08 pm, edited 1 time in total.
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jmehta - Name: Jayesh Mehta MD
Re: Report on Myeloma Trials at UAMS
Hello Nick!
It seems that you were offended by specific scientific terms. Experiment is the very basis of all science, and i was surprised that you took offense. I will endeavor to respond to you with lots of civility. I apologize for not presuming the word experiment would be taken out of context in a thread on myeloma trials.
The pathogenesis of myeloma is not known and the testing for myeloma is not precise in terms of whether there is active disease, thus patients must make decisions without the scientific data to assure them it is the most effective choice. Many of the tests used for myeloma are surrogate tests which measure a protein. What is not known is if there are many cells producing a small amount of protein or a few cells producing a lot of protein. It simply is unknown. Thus the need for decisions in a vacuum. UAMs has no more statistically significant data than anyone else. In fact, as previously stated, their data is biased as it has a single source and there is no comparative data available.
I am making no assertions regarding whether the data is brazenly falsified, rather the assertion is there is not comparative data. As, an individual with an MBA, clearly you would recognize that Microsoft comparing it's products to itself only vs. it's competitors would not be helpful in the decision making process of selecting the most functional product.
I apologize for using the word ignorance, as I was ticked that a basic science term that is the foundation of discovery had even generated offense and being uninformed was the only reasoning that could account for that.
I need to note that statistical significance is not clinical significance. Here is a clear example of that:
http://skepticalscalpel.blogspot.com/2011/08/statistical-vs-clinical-significance.html
TT is not being used elsewhere because it has not been demonstrated to be superior therapy.
This is not about ego. The gold standard in medical therapy are randomized controlled trials which provide scientifically validated evidence of efficacy. For whatever reason, this standard and well-reccognized process is not possible with TT. Therefore, it is reasonable to conclude that it is not superior to all other available therapies and in fact can be very life-threatening therapy such that the risks outweigh the benefit.
No matter how many years of their own data is available at UAMS, it is not sufficient to make a judgment to submit to the therapy when there is no evidence that it is highly effective AS COMPARED to other treatment regimens. The protocol alone is highly toxic.
Many patients use many therapies, success is not driven by the numbers of patients who are willing to undergo the therapy. The physicians are speculating about cure as a concept, as there is not consensus even on what cure is, ergo we have terms such as 'operational' cure floating around. Before there can be consensus on cure, there would need to be consensus on diagnostic tests for myeloma, that aren't surrogate tests....and there isn't.
Single source data is the very opposite of proof in science and medicine. When other's are unable to replicate the therapeutic outcomes, it makes the original data suspect. That is the very basics of scientific inquiry and validated clinical outcomes.
I did not make Barlogie out to be an ogre. I clearly stated it was his therapeutic trials and methods that I consider radical, and there are many others in the scientific community who see the tandem high dose chemotherapy as extreme, simply on the basis that there is a high leukemia rate following high-dose chemotherapy without it being tandem. High dose chemotherapy is not specific to myeloma cells, it takes a significant toll on the normal biologic function of the individual and results in life long adverse effects that significantly diminish a patients quality of life. My overall view is that there does not seem to be a high enough regard for the quality of life of the patient post-therapy as the most toxic and gruelling regimen is consistently a part of TT1-3
"PLENTY of centers now pursue more aggressive therapy than they did a few years ago"
AND?....2 wrongs do not make a right. Ever more aggressive therapy is not necessarily effective therapy where the benefits outweigh the risks. I do not believe in the very concept of high-dose chemotherapy where the therapy basically kill as many normal cells as it takes IN HOPES of killing the myeloma cells...it has not worked in 40 years! If this type of therapeutic concept worked myeloma would not still be incurable in 2012. As long as the medical community is using high-dose chemotherapy it will not progress towards managing or curing myeloma, as it has been demonstrated to be a failed concept, even if it dose have a very high revenue stream.
The newest therapeutic agents for myeloma that are resulting in CR, are NOT based on high-dose chemotherapy. Thank god! The light is coming on. In the future tandem high-dose will likely have the same level of respect as leech therapy.
"My point was that treating it more aggressively – as was done in pediatric Leukemia, it’s not like he made up the concept of Total Therapy – was something Bart did that is now being followed. It’s not about using an IMID off-label. It’s about using Velcade and Revlimid in frontline therapy rather than reserving it for recurrence or even salvage therapy, which is how it was being routinely used a few years ago."
OK, here we go again. You sit on panels with physicians, and yet terms like off-label appear to be unclear. Anytime a drug is used for something other than it's FDA indications, that is considered off-label use. Using bortezomib and lenalidamide for NDMM patients or 'frontline' would fall into the category of off-label use. This is how the vast majority of chemotherapy is used. And, the very idea of 'saving agents' for relapse is a rationale that is not medically supportable...it is like 'saving the best for last'...GMAB!
"It’s difficult not to be emotional in a response since this character assassination borders on Godwinism"
Ha!!...conjecture on what can be argued is not character assassination. Further, given that i am not in the medical community, I beg to differ. I learned a lot about what medical peers think of the program at MIRT. The most common response was 'cowboy'. 'radical' and 'extreme'
Maintenance therapy is going to be a mainstay of myeloma therapy. Based on the evidence available, historically, patients relapse ..extending PFS..is the goal. As the myeloma is not eradicated, even with TT1-3, it makes sense to have patients maintain their MRD levels with maintenance therapy. iOW's even if MIRT is taking patients off therapy that is not indicative of the best practice, nor revenues given that relapse provides greater revenue, if the patient has to again under high-dose chemotherapy with salvage stem cells. Maintenance would be more cost-effective and over greater benefits vs. risk than relapse therapy with HDT.
It is wonderful that you have a personal relationship with Bart, but that relationship is really not the thread topic. It is disconcerting in fact as it underscores the 'cult-like' atmosphere patients describe at MIRT and that numerous acolytes extoll about the program immersion. Very disconcerting. A lot of emotional investment that appears to be well beyond how patients from other myeloma centers describe their therapy. Nor have I made a personal attack on Bart. You are emotionally invested it appears, which again is consistent with patients from MIRT. I suspect Bart is a nice person, but his being a nice individual does not change the deep distrust for the therapeutic methods and therapies at MIRT.
"This is a patently false statement"
Prove it.
The article which Mark used to initiate the thread was indeed in a peer-reviewed journal.
Nice chatting with you Nick,
Toodles.
It seems that you were offended by specific scientific terms. Experiment is the very basis of all science, and i was surprised that you took offense. I will endeavor to respond to you with lots of civility. I apologize for not presuming the word experiment would be taken out of context in a thread on myeloma trials.
The pathogenesis of myeloma is not known and the testing for myeloma is not precise in terms of whether there is active disease, thus patients must make decisions without the scientific data to assure them it is the most effective choice. Many of the tests used for myeloma are surrogate tests which measure a protein. What is not known is if there are many cells producing a small amount of protein or a few cells producing a lot of protein. It simply is unknown. Thus the need for decisions in a vacuum. UAMs has no more statistically significant data than anyone else. In fact, as previously stated, their data is biased as it has a single source and there is no comparative data available.
I am making no assertions regarding whether the data is brazenly falsified, rather the assertion is there is not comparative data. As, an individual with an MBA, clearly you would recognize that Microsoft comparing it's products to itself only vs. it's competitors would not be helpful in the decision making process of selecting the most functional product.
I apologize for using the word ignorance, as I was ticked that a basic science term that is the foundation of discovery had even generated offense and being uninformed was the only reasoning that could account for that.
I need to note that statistical significance is not clinical significance. Here is a clear example of that:
http://skepticalscalpel.blogspot.com/2011/08/statistical-vs-clinical-significance.html
TT is not being used elsewhere because it has not been demonstrated to be superior therapy.
This is not about ego. The gold standard in medical therapy are randomized controlled trials which provide scientifically validated evidence of efficacy. For whatever reason, this standard and well-reccognized process is not possible with TT. Therefore, it is reasonable to conclude that it is not superior to all other available therapies and in fact can be very life-threatening therapy such that the risks outweigh the benefit.
No matter how many years of their own data is available at UAMS, it is not sufficient to make a judgment to submit to the therapy when there is no evidence that it is highly effective AS COMPARED to other treatment regimens. The protocol alone is highly toxic.
Many patients use many therapies, success is not driven by the numbers of patients who are willing to undergo the therapy. The physicians are speculating about cure as a concept, as there is not consensus even on what cure is, ergo we have terms such as 'operational' cure floating around. Before there can be consensus on cure, there would need to be consensus on diagnostic tests for myeloma, that aren't surrogate tests....and there isn't.
Single source data is the very opposite of proof in science and medicine. When other's are unable to replicate the therapeutic outcomes, it makes the original data suspect. That is the very basics of scientific inquiry and validated clinical outcomes.
I did not make Barlogie out to be an ogre. I clearly stated it was his therapeutic trials and methods that I consider radical, and there are many others in the scientific community who see the tandem high dose chemotherapy as extreme, simply on the basis that there is a high leukemia rate following high-dose chemotherapy without it being tandem. High dose chemotherapy is not specific to myeloma cells, it takes a significant toll on the normal biologic function of the individual and results in life long adverse effects that significantly diminish a patients quality of life. My overall view is that there does not seem to be a high enough regard for the quality of life of the patient post-therapy as the most toxic and gruelling regimen is consistently a part of TT1-3
"PLENTY of centers now pursue more aggressive therapy than they did a few years ago"
AND?....2 wrongs do not make a right. Ever more aggressive therapy is not necessarily effective therapy where the benefits outweigh the risks. I do not believe in the very concept of high-dose chemotherapy where the therapy basically kill as many normal cells as it takes IN HOPES of killing the myeloma cells...it has not worked in 40 years! If this type of therapeutic concept worked myeloma would not still be incurable in 2012. As long as the medical community is using high-dose chemotherapy it will not progress towards managing or curing myeloma, as it has been demonstrated to be a failed concept, even if it dose have a very high revenue stream.
The newest therapeutic agents for myeloma that are resulting in CR, are NOT based on high-dose chemotherapy. Thank god! The light is coming on. In the future tandem high-dose will likely have the same level of respect as leech therapy.
"My point was that treating it more aggressively – as was done in pediatric Leukemia, it’s not like he made up the concept of Total Therapy – was something Bart did that is now being followed. It’s not about using an IMID off-label. It’s about using Velcade and Revlimid in frontline therapy rather than reserving it for recurrence or even salvage therapy, which is how it was being routinely used a few years ago."
OK, here we go again. You sit on panels with physicians, and yet terms like off-label appear to be unclear. Anytime a drug is used for something other than it's FDA indications, that is considered off-label use. Using bortezomib and lenalidamide for NDMM patients or 'frontline' would fall into the category of off-label use. This is how the vast majority of chemotherapy is used. And, the very idea of 'saving agents' for relapse is a rationale that is not medically supportable...it is like 'saving the best for last'...GMAB!
"It’s difficult not to be emotional in a response since this character assassination borders on Godwinism"
Ha!!...conjecture on what can be argued is not character assassination. Further, given that i am not in the medical community, I beg to differ. I learned a lot about what medical peers think of the program at MIRT. The most common response was 'cowboy'. 'radical' and 'extreme'
Maintenance therapy is going to be a mainstay of myeloma therapy. Based on the evidence available, historically, patients relapse ..extending PFS..is the goal. As the myeloma is not eradicated, even with TT1-3, it makes sense to have patients maintain their MRD levels with maintenance therapy. iOW's even if MIRT is taking patients off therapy that is not indicative of the best practice, nor revenues given that relapse provides greater revenue, if the patient has to again under high-dose chemotherapy with salvage stem cells. Maintenance would be more cost-effective and over greater benefits vs. risk than relapse therapy with HDT.
It is wonderful that you have a personal relationship with Bart, but that relationship is really not the thread topic. It is disconcerting in fact as it underscores the 'cult-like' atmosphere patients describe at MIRT and that numerous acolytes extoll about the program immersion. Very disconcerting. A lot of emotional investment that appears to be well beyond how patients from other myeloma centers describe their therapy. Nor have I made a personal attack on Bart. You are emotionally invested it appears, which again is consistent with patients from MIRT. I suspect Bart is a nice person, but his being a nice individual does not change the deep distrust for the therapeutic methods and therapies at MIRT.
"This is a patently false statement"
Prove it.
The article which Mark used to initiate the thread was indeed in a peer-reviewed journal.
Nice chatting with you Nick,
Toodles.
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Report on Myeloma Trials at UAMS
Thank you so much Dr. Mehta for the in-depth reply!!
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Report on Myeloma Trials at UAMS
Mark -
Thank you for your post.
I may have been unclear, but my point had nothing to do with MAYO's opinion of a cure. I mentioned that only to clearly identify the Dr. as someone who disagreed fundamentally with Dr. Barlogie.
The point of my post was to cite a doctor from a respected institution that is anything but a toady to Dr. Barlogie and to provide his comments on the good that Dr. Barlogie has done for Myeloma patients generally.
I believe that much should be clear from his quote. If there are doubters, I can provide a link to his presentation where he speaks those words.
Mark wrote:
> Hi Nick,
>
> I was happy to read of your recent test results. Hopefully they continue.
>
> I do not believe that you properly represented Dr. Rajkumars views on the
> curability of myeloma. In the much discussed "Cure vs Control"
> debate paper he published, this is what he wrote:
>
> "Third, in most cases, it is probably impossible (with the possible
> exception of allogeneic transplantation where true complete eradication is
> possible for a minority of patients), unnecessary, and prohibitively toxic
> to attempt to eradicate all clonal plasma cells."
>
> "Fourth, the tests used to define CR in multiple myeloma are still
> inadequate and often vary considerably between laboratories. Although CR
> defined using molecular methods with patient-specific primers after
> allogeneic transplantation is more prolonged,39 it cannot predict cure with
> certainty."
>
> "In clinical practice, we prefer the control approach for most
> patients, acknowledging that high-risk subgroups need a more aggressive
> approach targeting CR or cure. For example, younger patients may opt for
> early intensive strategies, such as allogeneic transplantation, accepting
> high treatment-related mortality in exchange for a chance at long-term
> survival."
>
> http://bloodjournal.hematologylibrary.org/content/118/12/3205.long
>
> Just because a Doctor does not think "total therapy" is a cure,
> it does not mean that the Doctor does not think myeloma is a curable
> disease. I did a myeloablative allo 8 months after diagnosis, while I was
> in my first CR. I know that type of aggressive therapy is not often
> offered, but there are some that do it. You mentioned the panel discussion
> discussion that you were part of. Dr. Vij stated he offered allos to
> younger patients. I believe most Doctors agree myeloma is curable in the
> context of allo transplantation.
>
> Mark
Thank you for your post.
I may have been unclear, but my point had nothing to do with MAYO's opinion of a cure. I mentioned that only to clearly identify the Dr. as someone who disagreed fundamentally with Dr. Barlogie.
The point of my post was to cite a doctor from a respected institution that is anything but a toady to Dr. Barlogie and to provide his comments on the good that Dr. Barlogie has done for Myeloma patients generally.
I believe that much should be clear from his quote. If there are doubters, I can provide a link to his presentation where he speaks those words.
Mark wrote:
> Hi Nick,
>
> I was happy to read of your recent test results. Hopefully they continue.
>
> I do not believe that you properly represented Dr. Rajkumars views on the
> curability of myeloma. In the much discussed "Cure vs Control"
> debate paper he published, this is what he wrote:
>
> "Third, in most cases, it is probably impossible (with the possible
> exception of allogeneic transplantation where true complete eradication is
> possible for a minority of patients), unnecessary, and prohibitively toxic
> to attempt to eradicate all clonal plasma cells."
>
> "Fourth, the tests used to define CR in multiple myeloma are still
> inadequate and often vary considerably between laboratories. Although CR
> defined using molecular methods with patient-specific primers after
> allogeneic transplantation is more prolonged,39 it cannot predict cure with
> certainty."
>
> "In clinical practice, we prefer the control approach for most
> patients, acknowledging that high-risk subgroups need a more aggressive
> approach targeting CR or cure. For example, younger patients may opt for
> early intensive strategies, such as allogeneic transplantation, accepting
> high treatment-related mortality in exchange for a chance at long-term
> survival."
>
> http://bloodjournal.hematologylibrary.org/content/118/12/3205.long
>
> Just because a Doctor does not think "total therapy" is a cure,
> it does not mean that the Doctor does not think myeloma is a curable
> disease. I did a myeloablative allo 8 months after diagnosis, while I was
> in my first CR. I know that type of aggressive therapy is not often
> offered, but there are some that do it. You mentioned the panel discussion
> discussion that you were part of. Dr. Vij stated he offered allos to
> younger patients. I believe most Doctors agree myeloma is curable in the
> context of allo transplantation.
>
> Mark
-
nvandyk
Re: Report on Myeloma Trials at UAMS
This thread is now open again after we temporarily closed it earlier this morning to review some of the most recent postings.
As we go forward with the discussion, could we all try to keep in mind a few things?
First, let's try as much as possible to stay on topic and not get into personal attacks and accusations about other people's motivations.
Second, for those of you who already have posted quite a bit, it might serve the discussion better if, for a while, you let others step in and add their perspective or raise whatever questions they have.
We are fortunate that several myeloma specialists are participating in this discussion and debating important issues related to the treatment of multiple myeloma.
Therefore, let us all try to conduct ourselves in a way that respects the significance of the discussion, adds value to it, and reflects as positively as possible on the ability of myeloma patients and cargivers to carry out fair and objective discussion.
Thank you!
Boris Simkovich
Publisher, The Myeloma Beacon
As we go forward with the discussion, could we all try to keep in mind a few things?
First, let's try as much as possible to stay on topic and not get into personal attacks and accusations about other people's motivations.
Second, for those of you who already have posted quite a bit, it might serve the discussion better if, for a while, you let others step in and add their perspective or raise whatever questions they have.
We are fortunate that several myeloma specialists are participating in this discussion and debating important issues related to the treatment of multiple myeloma.
Therefore, let us all try to conduct ourselves in a way that respects the significance of the discussion, adds value to it, and reflects as positively as possible on the ability of myeloma patients and cargivers to carry out fair and objective discussion.
Thank you!
Boris Simkovich
Publisher, The Myeloma Beacon
-
Boris Simkovich - Name: Boris Simkovich
Founder
The Myeloma Beacon
Re: Report on Myeloma Trials at UAMS
One other quick reminder to everyone ... The original focus of this discussion thread was an unpublished report raising concerns about data in published UAMS clinical trial results.
In particular, the report contends that results from UAMS clinical trials show a higher-than-expected share of all deaths being due to "unknown" or "indeterminate" causes. The report also describes why such results (if they are true) should be a concern.
The focus of that report really should be the core focus of this discussion thread.
I am not saying that closely related concerns can't be raised and discussed as well. Such discussion can contribute further to the value of this thread.
However, let's always try to remember the original focus of the discussion, and not allow discussion to deviate too far away from it.
In particular, the report contends that results from UAMS clinical trials show a higher-than-expected share of all deaths being due to "unknown" or "indeterminate" causes. The report also describes why such results (if they are true) should be a concern.
The focus of that report really should be the core focus of this discussion thread.
I am not saying that closely related concerns can't be raised and discussed as well. Such discussion can contribute further to the value of this thread.
However, let's always try to remember the original focus of the discussion, and not allow discussion to deviate too far away from it.
-
Boris Simkovich - Name: Boris Simkovich
Founder
The Myeloma Beacon
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