HI Terry!!
"I was happy to see Dr. Shain posting again after "being away" for a while. So I was doubly disappointed when the first response to the doctor's lengthy posting was as rude and inconsiderate as Ma Larkey's."
ITA!!!!...
& he read the entire thread first too!!
Can't ask for more due diligence!!
Thanks Dr. Shain!!
Forums
Re: Steve's story and should I get a SCT?
Quite a sequence of responses to my post from Tuesday. Welcome back to the Beacon. But the passion, enthusiasm, and true interest in myeloma is one of the major reasons that I enjoy taking care of my myeloma patients and participating in forums such as the Beacon.
HDM-ASCT should evoke a number of emotional responses. Because as suzierose and others pointed out it is not an "easy" procedure. However, it remains an important part of myeloma therapy - even in the setting of proteasome inhibitors and IMIDs. Where, when, and if high-dose melphalan is incorporated is a moving target.
With novel agents such as Revlimid and Velcade, things have become much more interesting. I and many other myeloma docs still recommend HDM-ASCT early rather than late. However, as I stated, outcomes of early prospective studies indicated that outcomes were equivalent in terms of overall survival (Fermand et al Blood 1998) before the novel agents between early and delayed HDM-ASCT. The referenced study suggested improved quality of life measures with early transplant.
In a more contemporary setting (retrospective study) Dr. Kumar (Mayo Clinic) published a retrospective analysis comparing early versus delayed therapy (Kumar Cancer 2012) in patients following IMiD induction therapy (thalidomide/dex or Rev/dex). It again suggested equivalent outcomes. Unfortunately due to the retrospective nature of the study quality of life measures were not addressed.
So, early versus delayed therapy does appear to be equivalent. To this end, the decision of when remains up to the patient, the caregivers, and the physician. And as I stated earlier every decision is based on a number of factors (patient specific and disease specific).
Again, we await the day that when the need for transplant is completely unnecessary. However, I do not feel that we have reached that point.
That said, the early data looking at CRD (carfilzomib, Rev, dex) in the upfront setting will continue to push this question.
Lastly, everyone should remain passionate about this issues, about their care, or the care of their loved ones. High-dose therapy is NOT to be taken lightly, but should not be ignored as an important component of our arsenal to control this mortal disease.
HDM-ASCT should evoke a number of emotional responses. Because as suzierose and others pointed out it is not an "easy" procedure. However, it remains an important part of myeloma therapy - even in the setting of proteasome inhibitors and IMIDs. Where, when, and if high-dose melphalan is incorporated is a moving target.
With novel agents such as Revlimid and Velcade, things have become much more interesting. I and many other myeloma docs still recommend HDM-ASCT early rather than late. However, as I stated, outcomes of early prospective studies indicated that outcomes were equivalent in terms of overall survival (Fermand et al Blood 1998) before the novel agents between early and delayed HDM-ASCT. The referenced study suggested improved quality of life measures with early transplant.
In a more contemporary setting (retrospective study) Dr. Kumar (Mayo Clinic) published a retrospective analysis comparing early versus delayed therapy (Kumar Cancer 2012) in patients following IMiD induction therapy (thalidomide/dex or Rev/dex). It again suggested equivalent outcomes. Unfortunately due to the retrospective nature of the study quality of life measures were not addressed.
So, early versus delayed therapy does appear to be equivalent. To this end, the decision of when remains up to the patient, the caregivers, and the physician. And as I stated earlier every decision is based on a number of factors (patient specific and disease specific).
Again, we await the day that when the need for transplant is completely unnecessary. However, I do not feel that we have reached that point.
That said, the early data looking at CRD (carfilzomib, Rev, dex) in the upfront setting will continue to push this question.
Lastly, everyone should remain passionate about this issues, about their care, or the care of their loved ones. High-dose therapy is NOT to be taken lightly, but should not be ignored as an important component of our arsenal to control this mortal disease.
-
Dr. Ken Shain - Name: Ken Shain, M.D., Ph.D.
Beacon Medical Advisor
Re: Steve's story and should I get a SCT?
Hi Dr Shain
Thank you for all of that info. I am a Smoldering Patient. I do have a chromosome 13 deletion a chromosome 15 Trisomy and a Translocation (t 4-14). I am confused about having an upfront SCT if and when the time comes. My current Oncologist is very adamant about an upfront SCT. I'm not really sure where those risk factors come into play as far as determining when to have an SCT. Or do they? I'm sure other factors come into play but those are variables now as I am not at that point.
Thank You
Art
Thank you for all of that info. I am a Smoldering Patient. I do have a chromosome 13 deletion a chromosome 15 Trisomy and a Translocation (t 4-14). I am confused about having an upfront SCT if and when the time comes. My current Oncologist is very adamant about an upfront SCT. I'm not really sure where those risk factors come into play as far as determining when to have an SCT. Or do they? I'm sure other factors come into play but those are variables now as I am not at that point.
Thank You
Art
-
Art - Name: Art
- Who do you know with myeloma?: Self
- When were you/they diagnosed?: 12/2011
- Age at diagnosis: 40
Re: Steve's story and should I get a SCT?
Hi All, Thanks Dr. Shain for your views on ASCT, as well as other treatments. I did have an ASCT after induction chemo and harvesting, all within a time frame of less than six months, then did another year of 'maintenance'. I realize that all of these treatments are now being scrutinized as to safety and long term efficacy, and also as to when and if to undergo a transplant of either variety, but that was 3 years ago now. I appreciate Dr. Shain's info on the fact that the treatments were probably the best for me anyhow (am not a 'high risk' patient, it seems).
I just wanted to say that as far as QOL goes, mine is good right now. Have been off the chemo drugs for 13 months ....and am back to most of what I could do before, but am older and wiser now, and more cautious too! Because I was badly injured with vertebral fractures at the time of my diagnosis, my QOL at that time was lousy actually! So since I was already not very well, it didn't make a whole lot of difference to undergo a stem cell transplant also. I never would have believed then just how much better I would feel in a year. Of course I hope that this state of being carries on as it is, but at least so far I have gained a lot in QOL. I would not have survived this long without at least the induction therapy.
I just wanted to say that as far as QOL goes, mine is good right now. Have been off the chemo drugs for 13 months ....and am back to most of what I could do before, but am older and wiser now, and more cautious too! Because I was badly injured with vertebral fractures at the time of my diagnosis, my QOL at that time was lousy actually! So since I was already not very well, it didn't make a whole lot of difference to undergo a stem cell transplant also. I never would have believed then just how much better I would feel in a year. Of course I hope that this state of being carries on as it is, but at least so far I have gained a lot in QOL. I would not have survived this long without at least the induction therapy.
-
Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: Steve's story and should I get a SCT?
Nancy,
I am glad to hear that you are doing well off therapy and I hope that you continue to do well off therapy. One of the original byproducts of HDM-ASCT was to be off chemo. However, this paradigm is changing in the evolving era of maintenance therapy. Your are an excellent example of a success with transplant.
Art,
As a smoldering patient, your high risk cytogenetics (FISH) are not as helpful in predicting when you will progress to active disease (hopefully not for a long time). But you are correct they will have a bearing on your disease once therapy is initiated.
As I have stated in this thread previously, I am a proponent of early transplant for a number of reasons, especially if your payor does not cover harverst and storage. For instance, early transplant means that that you received a "second line" of therapy before developing resistance to your induction/primary line of therapy and those drugs are likely to be more useful for future relapses (I believe this is being discussed in another post).
The reality of high risk disease is that we do not have the best answers. The greatest improvement in myeloma has been in the standard risk patients and less so for high risk. If you were my patient, your therapy would be three agent therapy (CyBorD or RVD) for 6 cycles, HDM-ASCT, and maintenance Revlimid until progression. The caveats are your age, performance status and other clinical and physiological issues that you may have.
But as listed above early vs delayed transplant are "relatively" equivalent. And as you can see in this and other postings you will hear a number of points of view.
I am glad to hear that you are doing well off therapy and I hope that you continue to do well off therapy. One of the original byproducts of HDM-ASCT was to be off chemo. However, this paradigm is changing in the evolving era of maintenance therapy. Your are an excellent example of a success with transplant.
Art,
As a smoldering patient, your high risk cytogenetics (FISH) are not as helpful in predicting when you will progress to active disease (hopefully not for a long time). But you are correct they will have a bearing on your disease once therapy is initiated.
As I have stated in this thread previously, I am a proponent of early transplant for a number of reasons, especially if your payor does not cover harverst and storage. For instance, early transplant means that that you received a "second line" of therapy before developing resistance to your induction/primary line of therapy and those drugs are likely to be more useful for future relapses (I believe this is being discussed in another post).
The reality of high risk disease is that we do not have the best answers. The greatest improvement in myeloma has been in the standard risk patients and less so for high risk. If you were my patient, your therapy would be three agent therapy (CyBorD or RVD) for 6 cycles, HDM-ASCT, and maintenance Revlimid until progression. The caveats are your age, performance status and other clinical and physiological issues that you may have.
But as listed above early vs delayed transplant are "relatively" equivalent. And as you can see in this and other postings you will hear a number of points of view.
-
Dr. Ken Shain - Name: Ken Shain, M.D., Ph.D.
Beacon Medical Advisor
Re: Steve's story and should I get a SCT?
Hi Steve
Your pondering on:
"I wish there was more info available that compared people that achieved a CR and had a SCT soon afer diagnosis vs. those who achieved a CR and opted not have a SCT or waited"
Made me go out and look for answers. Can't say that I found one with your level of specificity regarding CR achieved during induction and preceeding to HDT-salvage vs delayed HDT-salvage.(HDT/S)
Partly this is because it is difficult to search for CR outcomes it wasn't until the poll this week that I used the term induction therapy...that resulted in better results and I think the information is worthwhile knowing in terms of history as it puts us on common footing and allows us to see how multiple myeloma therapy evolved to the point we are presently at such that there are multiple views/perspectives even amongst the experts.
I hope that if my understanding is not accurate one of the Beacon Advisors will be happy to jump in and offer more precise and accurate outcomes. Here is what I have learned thus far:
History of Induction Therapy...from 2008 ASH educational book
The goal of induction therapy is 2 achieve complete remission. The achievement of CR was so rare in multiple myeloma using conventional chemotherapy that the term 'induction' was not even used, it was called initial therapy instead. The rarity of CR was what ushered in the era of HDT as it was impossible to demonstrate any benefit of CR . Given that CR was achieved in less than 5% of cases with melphan/prednison (due to lethal toxicity without salvage) and in less than 10% of cases with dexamethasone based regimens of VAD (vincristine/adriamycin/dex)
In 1996 IFM 90 was the the 1st trial to demonstrate HDT was superior to conventional chemotherapy (Attal NEJM)..thus HDT followed with salvage stem cells(HDT/S) became the standard of care as part of frontline therapy.
In 1999 Barlogie (Blood) increased CR from 10% to 30-40% with dose intensification and tandem HDT/S.
In 2006, Marco (Blood) showed that CR was not improved with HDT/S vs VAD.
In 2007 vandeVelde found that CR following induction correlated with longer PFS and longer OS as did VGPR (defined as 90% reduction in Mserum component) than in pts achieving PR.
In the same year, HOVON24 trial (Sonneveld) showed that tandem vs single HDT/S resulted in increased PFS as well.
These two trials demonstrating the impact of CR on PFS produced two outcomes.
One was that clinical trial objectives were changed to demonstrate increase CR or CR/VGPR and secondly IMF revised the uniform criteria for multiple myeloma clinical trials (Durie 2006 Leukemia)
Most other cancers, since 70's, had these uniform trial criteria all along, but the definition of CR for induction therapy comparative outcomes for multiple myeloma were never established due to the rarity of the event. I do give IMF big credit for using response vs. remission..as the former is far less misleading than the latter, in the patients mind. i.e. remission does not equal cure.
So for 15 years prior to 2007 the best way to achieve CR was HDT followed by salvage with stem cells ( still can't wrap my mind around rescuing some one from the very outcome of the lethal therapy they submitted to as 'therapy')..where else is managing a lethal Adverse event considered 'therapy'..but I digress.
Next we enter the era of 'novel' agents.
The MCRIX study in 2007 (Blood) with the combination of thalidomide/dex used for induction, CR was low due to DVT but still CR was improved vs VAD.
Also in 2007 Harrouseau (Blood) in IFM 2005 trial demonstrates that induction with the combination bortezomib/dex improved CR response (35-55%) both pre and post HDT/S vs. VAD thus bortezombib/dex became the new backbone of induction therapy to which all other regimens are compared.
This was followed in 2008 by Richardson (JClinOncol) showing that bortezomib/dex regimens are better for mobilizing salvage stem cells vs. lenalidomide based regimens.
Pineda in 2008 (Br J Hemotology) showed sustained CR. When novel agents are used both before and after HDT/S, impressive preliminary results are obtained (2-year event-free survival and OS 84% and 87%, respectively.
Please note, none of this history regarding induction, where CR is a prognostic factor for PFS , takes into account the heterogeneity or risk stratification that is currently being elucidated within multiple myeloma disease, such that a pt with PR can result in longer PFS than a pt with CR.
So that is how we arrived at the point of present day induction therapy and the quagmire of whether HDT/S is essential if we are obtaining CR's comparable to those post HDT/S.
To date it has been demonstrated that induction followed immediately with HDT/S does not improve CR vs delayed HDT/S. So it becomes reasonable to ask, is HDT/S essential IF we are getting CR's (goal of induction) without them? Thus, making the decision highly personal given that even HDT/S fails (pts still die) and 50% do not reach CR with them.
Hope this background helps with how we arrived at this point.
End of HX.... this is cursory summary and my understanding..further details here:
http://asheducationbook.hematologylibrary.org/content/2008/1/306.full#T1
Still tackling your initial question though...
On another note, I can't figure out that "1 in the hand vs 2 in bush" analogy either...I think it may be a classic case of someone not understanding the phrase to begin with. Otherwise, ONE CR following induction is way better than any possible CR with HDT/S in other words how do you improve on the CR from induction?
Perhaps, one of the Beacon Advisors can share that.
I suspect a parameter change..and what they actually meant is longer PFS..but that is uncertain as noted above based on your personal risk stratification.. all CR's are not equivalent.
And as Dr. Shain notes in his response to ART:
" early transplant means that that you received a "second line" of therapy before developing resistance to your induction/primary line of therapy and those drugs are likely to be more useful for future relaspses (I believe this is being discussed in another post). The reality of high risk disease, is that we do not have the best answers"
Now, one could ask, should I do HDT/S before taking the novel agents that would have avoided those toxicities ...to have a backup?....hmmmmm..a real save the best for last quandry if I ever heard one.
Which brings us full circle to ...know your personal disease status,( get every test available to find tune that answer) your choices and your goals for PFS vs. QOL when deciding on the course of therapy that will give you personally the best outcomes.
Your pondering on:
"I wish there was more info available that compared people that achieved a CR and had a SCT soon afer diagnosis vs. those who achieved a CR and opted not have a SCT or waited"
Made me go out and look for answers. Can't say that I found one with your level of specificity regarding CR achieved during induction and preceeding to HDT-salvage vs delayed HDT-salvage.(HDT/S)
Partly this is because it is difficult to search for CR outcomes it wasn't until the poll this week that I used the term induction therapy...that resulted in better results and I think the information is worthwhile knowing in terms of history as it puts us on common footing and allows us to see how multiple myeloma therapy evolved to the point we are presently at such that there are multiple views/perspectives even amongst the experts.
I hope that if my understanding is not accurate one of the Beacon Advisors will be happy to jump in and offer more precise and accurate outcomes. Here is what I have learned thus far:
History of Induction Therapy...from 2008 ASH educational book
The goal of induction therapy is 2 achieve complete remission. The achievement of CR was so rare in multiple myeloma using conventional chemotherapy that the term 'induction' was not even used, it was called initial therapy instead. The rarity of CR was what ushered in the era of HDT as it was impossible to demonstrate any benefit of CR . Given that CR was achieved in less than 5% of cases with melphan/prednison (due to lethal toxicity without salvage) and in less than 10% of cases with dexamethasone based regimens of VAD (vincristine/adriamycin/dex)
In 1996 IFM 90 was the the 1st trial to demonstrate HDT was superior to conventional chemotherapy (Attal NEJM)..thus HDT followed with salvage stem cells(HDT/S) became the standard of care as part of frontline therapy.
In 1999 Barlogie (Blood) increased CR from 10% to 30-40% with dose intensification and tandem HDT/S.
In 2006, Marco (Blood) showed that CR was not improved with HDT/S vs VAD.
In 2007 vandeVelde found that CR following induction correlated with longer PFS and longer OS as did VGPR (defined as 90% reduction in Mserum component) than in pts achieving PR.
In the same year, HOVON24 trial (Sonneveld) showed that tandem vs single HDT/S resulted in increased PFS as well.
These two trials demonstrating the impact of CR on PFS produced two outcomes.
One was that clinical trial objectives were changed to demonstrate increase CR or CR/VGPR and secondly IMF revised the uniform criteria for multiple myeloma clinical trials (Durie 2006 Leukemia)
Most other cancers, since 70's, had these uniform trial criteria all along, but the definition of CR for induction therapy comparative outcomes for multiple myeloma were never established due to the rarity of the event. I do give IMF big credit for using response vs. remission..as the former is far less misleading than the latter, in the patients mind. i.e. remission does not equal cure.
So for 15 years prior to 2007 the best way to achieve CR was HDT followed by salvage with stem cells ( still can't wrap my mind around rescuing some one from the very outcome of the lethal therapy they submitted to as 'therapy')..where else is managing a lethal Adverse event considered 'therapy'..but I digress.
Next we enter the era of 'novel' agents.
The MCRIX study in 2007 (Blood) with the combination of thalidomide/dex used for induction, CR was low due to DVT but still CR was improved vs VAD.
Also in 2007 Harrouseau (Blood) in IFM 2005 trial demonstrates that induction with the combination bortezomib/dex improved CR response (35-55%) both pre and post HDT/S vs. VAD thus bortezombib/dex became the new backbone of induction therapy to which all other regimens are compared.
This was followed in 2008 by Richardson (JClinOncol) showing that bortezomib/dex regimens are better for mobilizing salvage stem cells vs. lenalidomide based regimens.
Pineda in 2008 (Br J Hemotology) showed sustained CR. When novel agents are used both before and after HDT/S, impressive preliminary results are obtained (2-year event-free survival and OS 84% and 87%, respectively.
Please note, none of this history regarding induction, where CR is a prognostic factor for PFS , takes into account the heterogeneity or risk stratification that is currently being elucidated within multiple myeloma disease, such that a pt with PR can result in longer PFS than a pt with CR.
So that is how we arrived at the point of present day induction therapy and the quagmire of whether HDT/S is essential if we are obtaining CR's comparable to those post HDT/S.
To date it has been demonstrated that induction followed immediately with HDT/S does not improve CR vs delayed HDT/S. So it becomes reasonable to ask, is HDT/S essential IF we are getting CR's (goal of induction) without them? Thus, making the decision highly personal given that even HDT/S fails (pts still die) and 50% do not reach CR with them.
Hope this background helps with how we arrived at this point.
End of HX.... this is cursory summary and my understanding..further details here:
http://asheducationbook.hematologylibrary.org/content/2008/1/306.full#T1
Still tackling your initial question though...
On another note, I can't figure out that "1 in the hand vs 2 in bush" analogy either...I think it may be a classic case of someone not understanding the phrase to begin with. Otherwise, ONE CR following induction is way better than any possible CR with HDT/S in other words how do you improve on the CR from induction?
Perhaps, one of the Beacon Advisors can share that.
I suspect a parameter change..and what they actually meant is longer PFS..but that is uncertain as noted above based on your personal risk stratification.. all CR's are not equivalent.
And as Dr. Shain notes in his response to ART:
" early transplant means that that you received a "second line" of therapy before developing resistance to your induction/primary line of therapy and those drugs are likely to be more useful for future relaspses (I believe this is being discussed in another post). The reality of high risk disease, is that we do not have the best answers"
Now, one could ask, should I do HDT/S before taking the novel agents that would have avoided those toxicities ...to have a backup?....hmmmmm..a real save the best for last quandry if I ever heard one.
Which brings us full circle to ...know your personal disease status,( get every test available to find tune that answer) your choices and your goals for PFS vs. QOL when deciding on the course of therapy that will give you personally the best outcomes.
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Steve's story and should I get a SCT?
Dr Shain
Thank you for your reply. So much to think about.
Thank you for your reply. So much to think about.
-
Art - Name: Art
- Who do you know with myeloma?: Self
- When were you/they diagnosed?: 12/2011
- Age at diagnosis: 40
Re: Steve's story and should I get a SCT?
Thanks Dr. Shain for your comments...I do feel very lucky that I have responded well to treatments so far. Also am fortunate to have received good medical advice and great care too! I enjoy reading the Beacon and also contributing what I can to encourage discussion and understanding of this complex disease. I certainly have learned a lot this year! It is only now that I have been through a lot of the myeloma treatments and experiences that I can understand it better! The Beacon itself is a great organization and if anyone wants to write a column, the editing help given to polish up one's article is really helpful. That has been a wonderful addition to my life lately.
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: Steve's story and should I get a SCT?
I'm wondering what about people who have just turned 65 and find out that Medicare will not pay to store your stem cells. It seems they don't have this choice to wait even if their quality of life is excellent and they'd like to. Has anyone else faced this??
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SherryB
29 posts
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