Hi everyone,
I write to you from Oslo, Norway!
I was diagnosed in 2007 with MGUS/SMM and collected stem cells the. I had no further treatments until now but rising IGG`s, M-Spike and last of all bone involvement made treatment start necessary just before easter. I had 3 rounds of of CyBorD (with 250ml Cycl at days 1 of cycle) and a bloodtest made just after the last injection of cycle 3 showed a still rather disappointing high level og the M-Spike. (Went from 3,7 to 1.0)
The doctors here usually always proceed without further attempting to lover the M-Spike, but I could get another 3x Vel/Dex without Cyclo and the plan is still to go to the scheduled ASCT starting June 18th
I am a bit worried and I am very close to "run" to my home country Germany to get more treatment before the ASCT trying to get back i line to a later point.
I am low risk ISS1 with T(11:14), but have found some strange indication of high risk profile in my flow cemetery result ( CD28+,CD117-) which could mean that a ASCT is altogether not a good idea!!!
Any comments will be helpful.
Thanks and hav a good day!
Regards from Oslo
Forums
Re: timing and results for proceed to 1. ASCT
Hi Christine!
I too am ISS I with significant cytogenetic abnormalities. According to FISH, I have virtually every single chromosome deletion/gain/translocation categorized as high risk, with the exception of t(11;14).
As you mentioned based on that cytogenetic profile I am not a good candidate for HighDose Chemo followed by the rescue procedure of my stem cells being transplanted to save me from the lethal does of the chemotherapy that I would have to submit to.
The key question for any patient though is did the induction therapy result in a CR?
Based on the history and clinical trial literature on multiple myeloma the only reason lethal dose-limiting chemotherapy became a standard of care for multiple myeloma was because they were not able to induce a complete 'remission' with conventional (non-lethal doses) chemotherapy. So, if a patient reaches a CR with the induction therapy why then should they move forward with lethal dose chemotherapy, as they have already achieved the outcome of CR without it?
multiple myeloma experts will give different views on that basic question...however the literature is clear on the fact that whether you submit to lethal dose chemo initially or at relapse the outcomes are the same.Why would timing make a difference if they are giving lethal doses? O that's right there is confusion cause patients think it is their stem cells that is the treatment..
Based on clinical data your original assessment is correct:
"Our results show that expression of both CD19 and CD28 as well as the absence of CD117 were associated with a significantly shorter progression free-survival (PFS) and overall survival (OS). Interestingly, the CD28 expression correlated with t(14;16) and del(17p), while CD117-negative patients were associated with t(4;14) and del(13q). Simultaneous assessment of CD28 and CD117 antigens allowed stratification of patients with multiple myeloma into three risk categories: poor risk (CD28 positive CD117 negative), intermediate (either both markers negative or both positive), and good risk (CD28 negative CD117 positive), with PFS rates of 30, 37, and 45 months, respectively (P = .01), and OS rates of 45, 68, and not reached, respectively (P = .0001)."
http://jco.ascopubs.org/content/26/16/2737.full
I suspect that patients grapple with whether to do a SCT because they believe it is a therapy when it is not. It is simply what they do to SAVE you after they infuse lethal does of chemotherapy to you to obliterate your immune system. In other words, an AUTO stem cell transplant is how they manage the adverse effects of the lethal dose it is NOT therapy.
I do not know of any other disease where managing a life-threatening adverse event is considered therapy. It is sheer bovine excrement to even call it therapy.
I too am ISS I with significant cytogenetic abnormalities. According to FISH, I have virtually every single chromosome deletion/gain/translocation categorized as high risk, with the exception of t(11;14).
As you mentioned based on that cytogenetic profile I am not a good candidate for HighDose Chemo followed by the rescue procedure of my stem cells being transplanted to save me from the lethal does of the chemotherapy that I would have to submit to.
The key question for any patient though is did the induction therapy result in a CR?
Based on the history and clinical trial literature on multiple myeloma the only reason lethal dose-limiting chemotherapy became a standard of care for multiple myeloma was because they were not able to induce a complete 'remission' with conventional (non-lethal doses) chemotherapy. So, if a patient reaches a CR with the induction therapy why then should they move forward with lethal dose chemotherapy, as they have already achieved the outcome of CR without it?
multiple myeloma experts will give different views on that basic question...however the literature is clear on the fact that whether you submit to lethal dose chemo initially or at relapse the outcomes are the same.Why would timing make a difference if they are giving lethal doses? O that's right there is confusion cause patients think it is their stem cells that is the treatment..
Based on clinical data your original assessment is correct:
"Our results show that expression of both CD19 and CD28 as well as the absence of CD117 were associated with a significantly shorter progression free-survival (PFS) and overall survival (OS). Interestingly, the CD28 expression correlated with t(14;16) and del(17p), while CD117-negative patients were associated with t(4;14) and del(13q). Simultaneous assessment of CD28 and CD117 antigens allowed stratification of patients with multiple myeloma into three risk categories: poor risk (CD28 positive CD117 negative), intermediate (either both markers negative or both positive), and good risk (CD28 negative CD117 positive), with PFS rates of 30, 37, and 45 months, respectively (P = .01), and OS rates of 45, 68, and not reached, respectively (P = .0001)."
http://jco.ascopubs.org/content/26/16/2737.full
I suspect that patients grapple with whether to do a SCT because they believe it is a therapy when it is not. It is simply what they do to SAVE you after they infuse lethal does of chemotherapy to you to obliterate your immune system. In other words, an AUTO stem cell transplant is how they manage the adverse effects of the lethal dose it is NOT therapy.
I do not know of any other disease where managing a life-threatening adverse event is considered therapy. It is sheer bovine excrement to even call it therapy.
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: timing and results for proceed to 1. ASCT
Hi again Christine,
I also found this information on prognostic criteria from Penn State which may be of interest to you.
It appears to be an excellent resource of clinical trials that looked at prognostic factors / outcomes with cytogenetic changes. For example, in this trial, t(11;14) was not a negative prognostic factor:
"Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome.
Blood. 2007 Apr 15;109(8):3489-95.
Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C, Leyvraz S, Michallet M, Yakoub-Agha I, Garderet L, Marit G, Michaux L, Voillat L, Renaud M, Grosbois B, Guillerm G, Benboubker L, Monconduit M, Thieblemont C, Casassus P, Caillot D, Stoppa AM, Sotto JJ, Wetterwald M, Dumontet C, Fuzibet JG, Azais I, Dorvaux V, Zandecki M, Bataille R, Minvielle S, Harousseau JL, Facon T, Mathiot C.
FISH was obtained in 1064 patients with newly diagnosed myeloma, screening for -13, -17p, t(11;14), t(4;14), hyperdiploidy, and MYC translocations. After multivariate analysis, only t(4;14) (14% of patients) and -17p (11% of patients) retained a negative prognostic value for both event-free survival and overall survival."
http://www.myelomapennstate.net/Contents/16b-Prognosis.htm
I also found this information on prognostic criteria from Penn State which may be of interest to you.
It appears to be an excellent resource of clinical trials that looked at prognostic factors / outcomes with cytogenetic changes. For example, in this trial, t(11;14) was not a negative prognostic factor:
"Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome.
Blood. 2007 Apr 15;109(8):3489-95.
Avet-Loiseau H, Attal M, Moreau P, Charbonnel C, Garban F, Hulin C, Leyvraz S, Michallet M, Yakoub-Agha I, Garderet L, Marit G, Michaux L, Voillat L, Renaud M, Grosbois B, Guillerm G, Benboubker L, Monconduit M, Thieblemont C, Casassus P, Caillot D, Stoppa AM, Sotto JJ, Wetterwald M, Dumontet C, Fuzibet JG, Azais I, Dorvaux V, Zandecki M, Bataille R, Minvielle S, Harousseau JL, Facon T, Mathiot C.
FISH was obtained in 1064 patients with newly diagnosed myeloma, screening for -13, -17p, t(11;14), t(4;14), hyperdiploidy, and MYC translocations. After multivariate analysis, only t(4;14) (14% of patients) and -17p (11% of patients) retained a negative prognostic value for both event-free survival and overall survival."
http://www.myelomapennstate.net/Contents/16b-Prognosis.htm
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: timing and results for proceed to 1. ASCT
Well the "rationale" that some oncologists put forth for an SCT is that it can knock out those last remaining tumor cells -- which of course it typically does not. And at what expense? And as you point out SR, if there is no compelling evidence that an early SCT is better than delayed SCT, why would one choose the former, toxic, approach? This disease is bad and frightening enough. It seems that many patients regard an SCT as something like getting your teeth pulled: annoying -- but not a big deal.
-
Shane W
Re: timing and results for proceed to 1. ASCT
Data for early vs delayed rescue from death SCT:
http://www.clinicaloncology.com//ViewArticle.aspx?ses=ogst&d=Hematologic+Malignancies&d_id=149&i=ISSUE%3a+May+2012&i_id=842&a_id=20893
http://www.clinicaloncology.com//ViewArticle.aspx?ses=ogst&d=Hematologic+Malignancies&d_id=149&i=ISSUE%3a+May+2012&i_id=842&a_id=20893
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: timing and results for proceed to 1. ASCT
Hi Shane!
" It seems that many patients regard an SCT as something like getting your teeth pulled: annoying -- but not a big deal."
Precisely. I would add abscessed tooth to your analogy where they suffer pervasive life-threating systemic infection.
I marvel at how patients provide all the issues they experience and sufffer as a result of being 'rescued' from death with their own cells. I constantly wonder, how is this, when most of the time folks complain about the severe not to mention life-threatening side effects that are a consequence of therapy.. Somehow, having to administer peripheral blood stem cells escapes this. I do not typically hear patients talk about how being in the hospital for up to 2 weeks or more due to side effects is a 'good' thing.
OTOH:
One of the factors that the multiple myeloma experts point to, understandably, is that they have shown an increase in OS with lethal dose chemo.
One of the questions, I have in that regard is that the data typically includes recovery from the lethal doses as part of the survival. Many patients experience long term problems such as impotence and diminished immune responses such that infections become more of a problem. If it takes patient, typically a year, before they begin to approach normalcy in terms of a functioning immune system is did they really gain? Also, could we be getting a skewed response in that the only folks that are talking about the 'rescue' is those that were? What about the folks that weren't? We don't get to hear from them. Are the 'rescued' a minority?
Personally, I would willingly suffer, if I knew I would be better but lethal doses don't assure that.
Also, the trials talk about how the 100 day mark post 'rescue' determines if you actually will have increased OS..as those not in CR at that point, go on to relapse even after having been rescued.
IOW's given that typically this is an older (55 plus) population and you could keep the disease at bay with low M spikes ..have you really gained from the high dose chemo, or is the survival more about how long it takes the body to come back from ablating the immune system?
I would like to see trials with the newer "novel" agents where they follow those with CR w/o high dose chemo in terms of survival vs. those who have a CR and go on to have high dose chemo. Is there a gain of survival in that population?
The literature seems to be unclear on that, partly I assume because the newer novel agents simply have not been around long enough and the comparisons are basically between patients who received aklylators as induction therapy and those who get lethal doses and those who do not as well as the heterogenetity of the disease itself.
Additionally, I wonder, why those who reach CR without lethal does can then relapse quicker than you can say 'jackflash' and those with PR can have longer PFS.. How does that happen? What is occuring with the disease? Typically, scientists speculate it is drug resistance, but is it? Could it be that the disease is so aggressive that even lethal doses don't eradicate it and it has nothing to do with the drug? Sorta like boxing, where the boxer knocks his opponent down in the first 2 rounds but the guy on the mat comes back and wins the fight in round 8? Did the winner just get caught off guard in the first couple of rounds and then roars back? That is not drug resistance, it is a far more powerful adversary who puts up his best in the latter rounds, no?
I wonder this because I am classified ISS one but yet due to the cytogenetics, I am not a good candidate, so what does that say about the parameters used to classify/stratify patients and the disease process itself?
So many questions.
" It seems that many patients regard an SCT as something like getting your teeth pulled: annoying -- but not a big deal."
Precisely. I would add abscessed tooth to your analogy where they suffer pervasive life-threating systemic infection.
I marvel at how patients provide all the issues they experience and sufffer as a result of being 'rescued' from death with their own cells. I constantly wonder, how is this, when most of the time folks complain about the severe not to mention life-threatening side effects that are a consequence of therapy.. Somehow, having to administer peripheral blood stem cells escapes this. I do not typically hear patients talk about how being in the hospital for up to 2 weeks or more due to side effects is a 'good' thing.
OTOH:
One of the factors that the multiple myeloma experts point to, understandably, is that they have shown an increase in OS with lethal dose chemo.
One of the questions, I have in that regard is that the data typically includes recovery from the lethal doses as part of the survival. Many patients experience long term problems such as impotence and diminished immune responses such that infections become more of a problem. If it takes patient, typically a year, before they begin to approach normalcy in terms of a functioning immune system is did they really gain? Also, could we be getting a skewed response in that the only folks that are talking about the 'rescue' is those that were? What about the folks that weren't? We don't get to hear from them. Are the 'rescued' a minority?
Personally, I would willingly suffer, if I knew I would be better but lethal doses don't assure that.
Also, the trials talk about how the 100 day mark post 'rescue' determines if you actually will have increased OS..as those not in CR at that point, go on to relapse even after having been rescued.
IOW's given that typically this is an older (55 plus) population and you could keep the disease at bay with low M spikes ..have you really gained from the high dose chemo, or is the survival more about how long it takes the body to come back from ablating the immune system?
I would like to see trials with the newer "novel" agents where they follow those with CR w/o high dose chemo in terms of survival vs. those who have a CR and go on to have high dose chemo. Is there a gain of survival in that population?
The literature seems to be unclear on that, partly I assume because the newer novel agents simply have not been around long enough and the comparisons are basically between patients who received aklylators as induction therapy and those who get lethal doses and those who do not as well as the heterogenetity of the disease itself.
Additionally, I wonder, why those who reach CR without lethal does can then relapse quicker than you can say 'jackflash' and those with PR can have longer PFS.. How does that happen? What is occuring with the disease? Typically, scientists speculate it is drug resistance, but is it? Could it be that the disease is so aggressive that even lethal doses don't eradicate it and it has nothing to do with the drug? Sorta like boxing, where the boxer knocks his opponent down in the first 2 rounds but the guy on the mat comes back and wins the fight in round 8? Did the winner just get caught off guard in the first couple of rounds and then roars back? That is not drug resistance, it is a far more powerful adversary who puts up his best in the latter rounds, no?
I wonder this because I am classified ISS one but yet due to the cytogenetics, I am not a good candidate, so what does that say about the parameters used to classify/stratify patients and the disease process itself?
So many questions.
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: timing and results for proceed to 1. ASCT
Wow. That summary -- and from May 2012 no less -- is pretty damm compelling that where one has the choice, delayed is the way to go. Unless of course, you really do enjoy HDT. But won't that reduce the upfront revenue stream for hospitals, given that HDT/SCTs typically cost 200-300K?
-
Shane W
Re: timing and results for proceed to 1. ASCT
Hi Shane!
You write:
" But won't that reduce the upfront revenue stream for hospitals, given that HDT/SCTs typically cost 200-300K?"
Seeeee, now you are going where i chose not to for fear of being called cynical. But yes, that is a fair question.
Especially given that lethal doses followed by 'rescue' has evolved to where folks consider auto SCT, as 'therapy". How did that happen? After all, the medical oath.. rule of medicine, is first do no harm.
So given that:
"The estimated median time to transplantation was 5.3 months in the early group and 44.5 months in the delayed group."
So 50% of delayed group may live 2 years with CR and the folks with high dose possibly 50% live an additional 2 years with the stem cell rescue? And at least a year of that lucky 50% is in 'recovery' post stem cell 'rescue'...is there really an increase in OS?
You write:
" But won't that reduce the upfront revenue stream for hospitals, given that HDT/SCTs typically cost 200-300K?"
Seeeee, now you are going where i chose not to for fear of being called cynical. But yes, that is a fair question.
Especially given that lethal doses followed by 'rescue' has evolved to where folks consider auto SCT, as 'therapy". How did that happen? After all, the medical oath.. rule of medicine, is first do no harm.
So given that:
"The estimated median time to transplantation was 5.3 months in the early group and 44.5 months in the delayed group."
So 50% of delayed group may live 2 years with CR and the folks with high dose possibly 50% live an additional 2 years with the stem cell rescue? And at least a year of that lucky 50% is in 'recovery' post stem cell 'rescue'...is there really an increase in OS?
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: timing and results for proceed to 1. ASCT
Thank you for your answers ! Lets see what June brings along 
Lots of good wines from Oslo
Lots of good wines from Oslo
Re: timing and results for proceed to 1. ASCT
I did bait you SR -- but with a heavy heart, as I do truly wish that SCTs were curative. If they were - and maybe total therapy by Barlogie really is -- then I would probably not think twice about it.
But the other thing to keep in mind about SCTs is that they arguably compromise your subsequent ability to respond to new therapies. In this optimistic age of chronic disease management, where there are dozens of drugs in various stages of development, there is much to merit in taking the marathon approach until the golden cocktail or regimen emerges. At least for a subset of patients.
And assuming that the newer drugs, such as carfilzomib, can buy someone CR and say 5-10 years of progression free survival, can a cure or chronic disease management approach be THAT FAR off?
Indeed, perhaps a greater research and clinical emphasis on maintenance following a CR (with the new drugs like carfilzomib) might be one long-term solution -- and here, there are a plethora of potential non-toxic approaches, including things like curcumin, perhaps vaccines, and maybe antibodies.
But the other thing to keep in mind about SCTs is that they arguably compromise your subsequent ability to respond to new therapies. In this optimistic age of chronic disease management, where there are dozens of drugs in various stages of development, there is much to merit in taking the marathon approach until the golden cocktail or regimen emerges. At least for a subset of patients.
And assuming that the newer drugs, such as carfilzomib, can buy someone CR and say 5-10 years of progression free survival, can a cure or chronic disease management approach be THAT FAR off?
Indeed, perhaps a greater research and clinical emphasis on maintenance following a CR (with the new drugs like carfilzomib) might be one long-term solution -- and here, there are a plethora of potential non-toxic approaches, including things like curcumin, perhaps vaccines, and maybe antibodies.
-
Shane W
14 posts
• Page 1 of 2 • 1, 2
Return to Treatments & Side Effects