JPC
Another way one might look the information reported is that regardless of the arm of treatment received the same percentage alive in each group at 3 years is not statistically different. What happens at 5 or more years will determine if a longer survival emerges in the patients in one arm versus the other, or not.
If after a longer time period those in the delayed transplant arm on having a transplant on relapse are found to have better overall survival than those with upfront transplants there would need to be an explanation as to why this would be the case.
Edna
Forums
Re: Initial results: key stem cell transplant clinical trial
Edna:
Agreed, but one more quick point. The ASCT arm is considered by many to be the higher side effect arm with the rougher treatment regime and side effects (I hedge just a bit because a few people do tolerate it well), so the non-transplant arm does not have to have better OS results to win, it just needs to tie. A tie goes to the non-transplant arm. Regards
Agreed, but one more quick point. The ASCT arm is considered by many to be the higher side effect arm with the rougher treatment regime and side effects (I hedge just a bit because a few people do tolerate it well), so the non-transplant arm does not have to have better OS results to win, it just needs to tie. A tie goes to the non-transplant arm. Regards
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JPC - Name: JPC
Re: Initial results: key stem cell transplant clinical trial
Cheryl, thanks for starting this thread and posting the 391 abstract (early vs. delayed SCT results). And thanks for posting the 395 abstract (MRI vs. PET-CT imaging results), Multibilly.
As many of you may know from some of my previous posts, I am in the US side of this clinical trial, and I was randomized into the early SCT arm. So I have been eagerly awaiting these papers. I'd heard rumors/speculation that the French side would publish initial results at ASH.
Multibilly, in answer to your question about why the US initial results are not being published at this time, what I've heard is that there still is not enough data from enough participants. In fact, the US side of the trial is still recruiting participants. As a caveat, I should add, of course, that I'm not connected with the trial in any official capacity other than as a participant, so anything I'm saying here is unofficial.
In looking at the data in the 391 abstract, a couple of things stood out to me as important. First of all, the 88% survival rate at 3 years for both arms is impressive. And encouraging to me since I'll hit the 3-year mark myself in a couple of months. I'm not counting my chickens before they are hatched, but it looks like I have a good shot at being on that 88% side of the equation.
I suggest that the 88% survival rate shows the effectiveness of triplet therapy with novel agents + maintenance, keeping in mind that even the early SCT arm got 5 cycles of this treatment (in addition to the SCT) and Revlimid maintenance for 1 year. This high survival rate may be skewed a bit by the fact that there was some screening regarding age (had to be <65 years old), co-morbidity, etc. so trial participants may have been healthier compared to "average" multiple myeloma patients. And this screening may account for the lower number of Stage III patients than you expected, Edna. Nevertheless, I find the 3-year OS rate very encouraging.
Similarly, I think the >50% CR rate across both arms was impressive. It's interesting that the early SCT arm had a significantly higher CR rate (58% to 46%). Seems like the early SCT did drive a deeper response in some patients here. It will be even more interesting to see if that higher CR rate translates into a longer OS when we get out further in time from the treatment.
One other data point that is important to me is the number of secondary malignancies. Across both arms, it is about 5.5%, which is in line with what other studies have found for Revlimid maintenance. And it's good news for me that there's not a large difference between the two arms on this measure (6.5% vs. 5.1% chance of secondary malignancy for early vs. late SCT arms), as some studies have suggested that there is an interaction between melphalan/SCT & Revlimid maintenance such that the combination of these treatments is what increases the likelihood of a secondary cancer, not Revlimid maintenance alone. Of course, this is another variable that can change as we get further out in time.
Finally, I have not heard any speculation on when the US initial results will be published. Obviously, those will be important too. Especially to me, assuming I'm still around.
Mike
As many of you may know from some of my previous posts, I am in the US side of this clinical trial, and I was randomized into the early SCT arm. So I have been eagerly awaiting these papers. I'd heard rumors/speculation that the French side would publish initial results at ASH.
Multibilly, in answer to your question about why the US initial results are not being published at this time, what I've heard is that there still is not enough data from enough participants. In fact, the US side of the trial is still recruiting participants. As a caveat, I should add, of course, that I'm not connected with the trial in any official capacity other than as a participant, so anything I'm saying here is unofficial.
In looking at the data in the 391 abstract, a couple of things stood out to me as important. First of all, the 88% survival rate at 3 years for both arms is impressive. And encouraging to me since I'll hit the 3-year mark myself in a couple of months. I'm not counting my chickens before they are hatched, but it looks like I have a good shot at being on that 88% side of the equation.
I suggest that the 88% survival rate shows the effectiveness of triplet therapy with novel agents + maintenance, keeping in mind that even the early SCT arm got 5 cycles of this treatment (in addition to the SCT) and Revlimid maintenance for 1 year. This high survival rate may be skewed a bit by the fact that there was some screening regarding age (had to be <65 years old), co-morbidity, etc. so trial participants may have been healthier compared to "average" multiple myeloma patients. And this screening may account for the lower number of Stage III patients than you expected, Edna. Nevertheless, I find the 3-year OS rate very encouraging.
Similarly, I think the >50% CR rate across both arms was impressive. It's interesting that the early SCT arm had a significantly higher CR rate (58% to 46%). Seems like the early SCT did drive a deeper response in some patients here. It will be even more interesting to see if that higher CR rate translates into a longer OS when we get out further in time from the treatment.
One other data point that is important to me is the number of secondary malignancies. Across both arms, it is about 5.5%, which is in line with what other studies have found for Revlimid maintenance. And it's good news for me that there's not a large difference between the two arms on this measure (6.5% vs. 5.1% chance of secondary malignancy for early vs. late SCT arms), as some studies have suggested that there is an interaction between melphalan/SCT & Revlimid maintenance such that the combination of these treatments is what increases the likelihood of a secondary cancer, not Revlimid maintenance alone. Of course, this is another variable that can change as we get further out in time.
Finally, I have not heard any speculation on when the US initial results will be published. Obviously, those will be important too. Especially to me, assuming I'm still around.
Mike
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mikeb - Name: mikeb
- Who do you know with myeloma?: self
- When were you/they diagnosed?: 2009 (MGUS at that time)
- Age at diagnosis: 55
Re: Initial results: key stem cell transplant clinical trial
While I see this reporting "interesting", I think it is based mostly on notions of care, circa 2008-2012.
A number of researchers, clinicians, and providers excitedly report increased utilization of doublet / triplet medication regimens, completely changing the game--including PFS / OS. ....and impressive results.
I think a study, based upon multiples of novel drugs, circa 2015, will be much more telling of the efficacy and utilization of transplants, in the future. Especially with the soon to be released oral based medications, such as proteasome inhibitors and IMiDs. Especially, as to quality of life considerations.
If we are to look at the gains between 2010-15 with the onset of numerous Novel drugs and therapies--we see it is a different ball game, than that reported by the French Division of this study. I suspect the US response to be similar.
Do you make decisions on Std of care treatments, based on 5 year old datum / therapies ?
Draw your conclusions carefully.
A corollary: While I do like my 2009 Sports Car, the 2015 models are much better, overall.
A number of researchers, clinicians, and providers excitedly report increased utilization of doublet / triplet medication regimens, completely changing the game--including PFS / OS. ....and impressive results.
I think a study, based upon multiples of novel drugs, circa 2015, will be much more telling of the efficacy and utilization of transplants, in the future. Especially with the soon to be released oral based medications, such as proteasome inhibitors and IMiDs. Especially, as to quality of life considerations.
If we are to look at the gains between 2010-15 with the onset of numerous Novel drugs and therapies--we see it is a different ball game, than that reported by the French Division of this study. I suspect the US response to be similar.
Do you make decisions on Std of care treatments, based on 5 year old datum / therapies ?
Draw your conclusions carefully.
A corollary: While I do like my 2009 Sports Car, the 2015 models are much better, overall.
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Rneb
Re: Initial results: key stem cell transplant clinical trial
I had smoldering myeloma for 3 years, bloods every month. As soon as it went active last year, I did not hesitate to have a SCT. Dreadful anemia that would have required lots of blood transfusions. I had induction therapy and am now post SCT 7 months (and still recovering). I prefer to have quality of life over longevity. I never hesitated at the SCT, and I am pleased I have had it done.
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Salzmav - Name: Salzmav
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: 2010
- Age at diagnosis: 52
Re: Initial results: key stem cell transplant clinical trial
Thanks everyone for your insightful analysis.
I would like to add to JPC 's point - that the "tie" in OS should go to the later transplant group.
Even if OS in the 2 arms end up tilting slightly in favor of the early transplant arm – which is something that we may not know for many years – the surviving 50 percent in the late transplant ARM may end up having a longer OS than their surviving counterparts in the early SCT arm because a significant number of them will still have an unused SCT in their armamentarium.
My guess is that many of us, when diagnosed, have heard median survival estimates and conclude that this is how long we will survive. The truth, with participants in a trial with 2 arm of approximately 350 participants, is that the odds of any of us having the exact OS result in either arm are about 175 to 1. The odds of us beating the median OS, however, are 50-50.
So to me, it is hard to review these preliminary results as validation or repudiation of the choices we have made relative to if or when to have an SCT. What I take from this preliminary report is that either approach is reasonable. And, both approaches have resulted in an outstanding 3 year PFS.
I would like to add to JPC 's point - that the "tie" in OS should go to the later transplant group.
Even if OS in the 2 arms end up tilting slightly in favor of the early transplant arm – which is something that we may not know for many years – the surviving 50 percent in the late transplant ARM may end up having a longer OS than their surviving counterparts in the early SCT arm because a significant number of them will still have an unused SCT in their armamentarium.
My guess is that many of us, when diagnosed, have heard median survival estimates and conclude that this is how long we will survive. The truth, with participants in a trial with 2 arm of approximately 350 participants, is that the odds of any of us having the exact OS result in either arm are about 175 to 1. The odds of us beating the median OS, however, are 50-50.
So to me, it is hard to review these preliminary results as validation or repudiation of the choices we have made relative to if or when to have an SCT. What I take from this preliminary report is that either approach is reasonable. And, both approaches have resulted in an outstanding 3 year PFS.
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MyelomaFighter
Re: Initial results: key stem cell transplant clinical trial
I know about this study and I will do more to read about the results. However, as a past transplant patient that followed the protocol that had me accept a transplant early after my diagnosis, I have a different opinion that is also shared by my multiple myeloma group.
We feel that a transplant is just another form of treatment. It is just another tool in the box and another choice of treatment available to us. We do not feel it is a superior treatment when measured against the success currently achieved using the available novel drugs. We are also very excited about the new drugs on the horizon.
We feel this way for the following reasons. If you have achieved excellent results using the novel drug a combination of drugs, why would you throw those results away and switch over to a stem cell transplant.
The down side of the transplant is the danger in undergoing a transplant where they destroy your bone marrow completely and the mortality risk that comes with that. It is a much more difficult treatment path in regards to its effect on your body. It took me two years to actually recover from the transplant and from my perspective you are never the same again.
On the other hand, if you can achieve the same level of result using the novel drugs with lessor side effects and whose side effects fade within days to weeks rather than months to years, why rush to a transplant?
Our bottom line is, we feel a transplant is better reserved as a last resort rather than front line. And if the data shows that the PFS is about the same then it doesn't seem to be of benefit.
My background, I have had multiple myeloma going on nine years. I have had every drug released for multiple myeloma without success from the following standpoint. As long as I am on any given drug my numbers drop slightly and do not rise until the drug no longer works or I stop using them. As soon as I stop within three weeks or less my numbers will advance dramatically. So no sustained response. I have never had a remission, and even the transplant failed. At the 100 day follow up, the doctor told me it was like I had never been treated. The transplant did nothing for me – zero response.
So for me its just a regimen of constant chemo with the various drugs and now days with various combinations of drugs. I still have stem cells banked so, who knows, maybe at some point there will be a pre-treatment protocol using these novel drugs that may make a transplant more effective. But for the difficulty required throughout process of the transplant, the recovery time and the ultimate damage to your body, in my opinion the transplant is not a good choice for a frontline treatment as compared to the success that is likely to be achieved using the novel drugs.
We feel that a transplant is just another form of treatment. It is just another tool in the box and another choice of treatment available to us. We do not feel it is a superior treatment when measured against the success currently achieved using the available novel drugs. We are also very excited about the new drugs on the horizon.
We feel this way for the following reasons. If you have achieved excellent results using the novel drug a combination of drugs, why would you throw those results away and switch over to a stem cell transplant.
The down side of the transplant is the danger in undergoing a transplant where they destroy your bone marrow completely and the mortality risk that comes with that. It is a much more difficult treatment path in regards to its effect on your body. It took me two years to actually recover from the transplant and from my perspective you are never the same again.
On the other hand, if you can achieve the same level of result using the novel drugs with lessor side effects and whose side effects fade within days to weeks rather than months to years, why rush to a transplant?
Our bottom line is, we feel a transplant is better reserved as a last resort rather than front line. And if the data shows that the PFS is about the same then it doesn't seem to be of benefit.
My background, I have had multiple myeloma going on nine years. I have had every drug released for multiple myeloma without success from the following standpoint. As long as I am on any given drug my numbers drop slightly and do not rise until the drug no longer works or I stop using them. As soon as I stop within three weeks or less my numbers will advance dramatically. So no sustained response. I have never had a remission, and even the transplant failed. At the 100 day follow up, the doctor told me it was like I had never been treated. The transplant did nothing for me – zero response.
So for me its just a regimen of constant chemo with the various drugs and now days with various combinations of drugs. I still have stem cells banked so, who knows, maybe at some point there will be a pre-treatment protocol using these novel drugs that may make a transplant more effective. But for the difficulty required throughout process of the transplant, the recovery time and the ultimate damage to your body, in my opinion the transplant is not a good choice for a frontline treatment as compared to the success that is likely to be achieved using the novel drugs.
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JonEman
Re: Initial results: key stem cell transplant clinical trial
Just a quick comment about the use of autologous stem cell transplants for newly diagnosed patients in the US ...
Only 12% of US patients in 2010 actually did an autologous transplant during the first year after diagnosis. I get the impression from the posters above that they think the number is higher and that it is declining. A lot of the posters here talk like an auto is commonly used therapy for newly diagnosed patients in the US.
Reference: M Al-Hamadani et al., "Use of autologous hematopoietic cell transplantation as initial therapy in multiple myeloma and the impact of socio-geo-demographic factors in the era of novel agents," American Journal of Hematology, Aug 2014 (full text of article)
Mark
Only 12% of US patients in 2010 actually did an autologous transplant during the first year after diagnosis. I get the impression from the posters above that they think the number is higher and that it is declining. A lot of the posters here talk like an auto is commonly used therapy for newly diagnosed patients in the US.
"Very effective combination chemotherapy using novel agents has become available in multiple myeloma. Its impact on the use of high-dose chemotherapy and autologous hematopoietic stem cell transplantation (AHCT) as part of initial therapy is unknown. Using the National Cancer Data Base, we studied the rate of upfront AHCT use among 137,409 newly diagnosed multiple myeloma patients from 1998 to 2010 in the United States and determined whether disparity exists among various sociodemographic as well as geographic subgroups.
Overall, 12,378 (9.0%) patients received AHCT as part of initial treatment. The use of upfront AHCT increased steadily from 5.2% in 1998 to 12.1% in 2010 (trend test, P < 0.001), with no sign of plateau. This was seen across all socio-geo-demographic subgroups except among patients treated in the Northeast, where the rate fell from 8.7% in 1998 to 6.6% in 2010.
In multivariable analysis, patients with the following characteristics were the least likely to receive AHCT (odds ratio):
- Year of diagnosis from 1998 to 2003 before the era of novel agents (0.67)
- Older age (0.35)
- Black race (0.58)
- Hispanic ethnicity (0.78)
- Low level of education or annual household income (0.55)
- Residence in a metro area (0.66)
- No or unknown medical insurance (0.30)
- Treatment at a community cancer center (0.16), and
- Treatment facility located in the Northeast region (0.54).
Even after the introduction of novel agents, the rate of upfront AHCT in multiple myeloma continues to increase annually. Significant disparities exist dependent on demographic, social, and geographic factors."
Reference: M Al-Hamadani et al., "Use of autologous hematopoietic cell transplantation as initial therapy in multiple myeloma and the impact of socio-geo-demographic factors in the era of novel agents," American Journal of Hematology, Aug 2014 (full text of article)
Mark
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Mark11
Re: Initial results: key stem cell transplant clinical trial
Hello, Mark:
Quick reply on your comment/stats. I would have to dig to get the reference, but recalling an article that I recently read: At diagnosis of multiple myeloma, about 50% are in the old / frail category, and would not be considered for transplant. Of the remaining 50% who are eligible for transplant, about half of those people elect transplant, so in real terms, for those who have a real choice, its about half. Of those who do not elect initial transplant, something like half of those will elect transplant at first relapse. So considering initial diagnosis and first relapse, its about 75% of transplant eligible patients that will elect transplant at initial diagnosis or first relapse, and of course the remaining 25% face the decision. So it is an issue for most people. Best Regards,
Quick reply on your comment/stats. I would have to dig to get the reference, but recalling an article that I recently read: At diagnosis of multiple myeloma, about 50% are in the old / frail category, and would not be considered for transplant. Of the remaining 50% who are eligible for transplant, about half of those people elect transplant, so in real terms, for those who have a real choice, its about half. Of those who do not elect initial transplant, something like half of those will elect transplant at first relapse. So considering initial diagnosis and first relapse, its about 75% of transplant eligible patients that will elect transplant at initial diagnosis or first relapse, and of course the remaining 25% face the decision. So it is an issue for most people. Best Regards,
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JPC - Name: JPC
Re: Initial results: key stem cell transplant clinical trial
JonEman
I can relate readily to your viewpoint. I myself have asked about whether I can store stem cells for a 'last ditch' attempt at treatment when nothing else works or is available here in the UK. My line of thought is just as yours. ASCT is just one treatment option amongst a mix that can be given along the course of the disease. Whether a patient accepts long term / life long drug treatment to control the disease or wants to have the option of a period drug free, post ASCT, is a personal issue. Some may feel fairly 'normal' in terms of quality of life in either situations, others will not.
Pat Killingsworth's column on his high risk strategy best encapsulates what I might want having come to that stage of my myeloma journey, but not before. There is less to loose, either in terms of survival or quality of life remaining, and much can be gained.
I noted that a fellow MMer, similar age and similar comorbidity had a ASCT with only 5 months before progression, before going on the same drug as myself, relapsing on that before I did and went onto third line, some 5 months before me and now is on fourth line. I could not say ASCT has given this person a quality of life experience with myeloma.
Rather than look at research statistics on median survivals etc. I tend to talk to and assess from people's actual experiences with treatment. Like you I have discovered there is nothing more about a transplant other than it is another treatment, working well with some and not with others. As to long term survival with triplet therapies incorporating novel drugs / regimes, researchers are not yet at the stage of being able to state that these give the same survival benefits as reported so frequently for ASCT up until now.
I do not not expect the research to provide me clear options for myself personally.
Mark 11
Aside from much older people in my clinic I have rarely come across people not having had a transplant as part of initial treatment. I think in Europe it is deemed a 'gold standard',at present.
I do not know why the percentage of figures for the transplants in the US is low. Any ideas?
Edna
I can relate readily to your viewpoint. I myself have asked about whether I can store stem cells for a 'last ditch' attempt at treatment when nothing else works or is available here in the UK. My line of thought is just as yours. ASCT is just one treatment option amongst a mix that can be given along the course of the disease. Whether a patient accepts long term / life long drug treatment to control the disease or wants to have the option of a period drug free, post ASCT, is a personal issue. Some may feel fairly 'normal' in terms of quality of life in either situations, others will not.
Pat Killingsworth's column on his high risk strategy best encapsulates what I might want having come to that stage of my myeloma journey, but not before. There is less to loose, either in terms of survival or quality of life remaining, and much can be gained.
I noted that a fellow MMer, similar age and similar comorbidity had a ASCT with only 5 months before progression, before going on the same drug as myself, relapsing on that before I did and went onto third line, some 5 months before me and now is on fourth line. I could not say ASCT has given this person a quality of life experience with myeloma.
Rather than look at research statistics on median survivals etc. I tend to talk to and assess from people's actual experiences with treatment. Like you I have discovered there is nothing more about a transplant other than it is another treatment, working well with some and not with others. As to long term survival with triplet therapies incorporating novel drugs / regimes, researchers are not yet at the stage of being able to state that these give the same survival benefits as reported so frequently for ASCT up until now.
I do not not expect the research to provide me clear options for myself personally.
Mark 11
Aside from much older people in my clinic I have rarely come across people not having had a transplant as part of initial treatment. I think in Europe it is deemed a 'gold standard',at present.
I do not know why the percentage of figures for the transplants in the US is low. Any ideas?
Edna
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