LibbyC wrote:
> Hi Dee777,
> Cure vs control. Would anyone who has/had myeloma actually believe their
> doctor if they say you are "cured". My first question would be
> "how do you know? to be followed with "what proof do you have?
Call me an optimist, but I would believe my doctor if he said I was cured if I had in fact gone through a series of targeted therapies and had a series of molecular response tests that showed absolutely zero MRD. I'm actually quite surprised that the Black Swan Initiative hasn't generated more discussion on this site and that more details (and news in general regarding multiple myeloma treatments) weren't forthcoming out of the IMW 2013
Forums
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Allo transplant cures?
Hi Multibilly,
I think the reason that their is not more "buzz" about Black Swan is that it likely will not apply to many current patients. While many patients say they would like a cure many myeloma patients are not comfortable with the therapies that have shown the ability to cure blood cancers. Most blood cancer patients are cured by immunotherapy (allo transplant) or strong upfront chemotherapy regimines (ex. R-CHOP for non-Hodgkin lymphoma). Most myeloma patients seem to want to go the "control" route with IMIDs and proteasome inhibitors. Unfortunately combos like Velcade/Revlimid/DEX and Kyprolis/Revlimid/DEX do not hit enough pathways to cure myeloma patients. Another paragraph from one of the articles about the great medical pioneer E Donnall Thomas after he passed away sums it up very well.
"Thomas was always mindful that his achievements depended on the courage of his patients. The dangers they faced and the suffering they endured enabled him to establish a therapy that has saved many lives and will save countless more. His life's work provides a foundation for broader future applications in the fields of regenerative medicine, gene and stem cell therapy."
Read more: http://www.smh.com.au/national/obituaries/nobel-laureate-gave-new-hope-to-cancer-victims-20121113-29a9t.html#ixzz2RlhetKzb
It takes a great Doctor like E Donnall Thomas and patients willing to do therapies that are curative to turn a disease from incurable to curable.
Mark
I think the reason that their is not more "buzz" about Black Swan is that it likely will not apply to many current patients. While many patients say they would like a cure many myeloma patients are not comfortable with the therapies that have shown the ability to cure blood cancers. Most blood cancer patients are cured by immunotherapy (allo transplant) or strong upfront chemotherapy regimines (ex. R-CHOP for non-Hodgkin lymphoma). Most myeloma patients seem to want to go the "control" route with IMIDs and proteasome inhibitors. Unfortunately combos like Velcade/Revlimid/DEX and Kyprolis/Revlimid/DEX do not hit enough pathways to cure myeloma patients. Another paragraph from one of the articles about the great medical pioneer E Donnall Thomas after he passed away sums it up very well.
"Thomas was always mindful that his achievements depended on the courage of his patients. The dangers they faced and the suffering they endured enabled him to establish a therapy that has saved many lives and will save countless more. His life's work provides a foundation for broader future applications in the fields of regenerative medicine, gene and stem cell therapy."
Read more: http://www.smh.com.au/national/obituaries/nobel-laureate-gave-new-hope-to-cancer-victims-20121113-29a9t.html#ixzz2RlhetKzb
It takes a great Doctor like E Donnall Thomas and patients willing to do therapies that are curative to turn a disease from incurable to curable.
Mark
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Mark
Re: Allo transplant cures?
Mark wrote:
> Hi Multibilly,
>
> I think the reason that their is not more "buzz" about Black Swan
> is that it likely will not apply to many current patients. While many
> patients say they would like a cure many myeloma patients are not
> comfortable with the therapies that have shown the ability to cure blood
> cancers.
Thanks Mark.
First off, I apologize to Blair77 if I hijacked this thread and got slightly off the original topic of allos, but the BSI trials start this year, right? And the treatment protocol will utilize specific novel agents (control routes) based on very specific molecular tests for each individual, right? And we could start to have the fruits of this effort in about 3 years if all goes well. Given the timing and the regiments that will be utilized, it seems like this would be a keen topic of interest for many MGUS, SMM and current multiple myeloma patients wrt cure(s) on the horizon. Maybe I'm missing something here?
> Hi Multibilly,
>
> I think the reason that their is not more "buzz" about Black Swan
> is that it likely will not apply to many current patients. While many
> patients say they would like a cure many myeloma patients are not
> comfortable with the therapies that have shown the ability to cure blood
> cancers.
Thanks Mark.
First off, I apologize to Blair77 if I hijacked this thread and got slightly off the original topic of allos, but the BSI trials start this year, right? And the treatment protocol will utilize specific novel agents (control routes) based on very specific molecular tests for each individual, right? And we could start to have the fruits of this effort in about 3 years if all goes well. Given the timing and the regiments that will be utilized, it seems like this would be a keen topic of interest for many MGUS, SMM and current multiple myeloma patients wrt cure(s) on the horizon. Maybe I'm missing something here?
-
Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Allo transplant cures?
Hi Multibilly, I agree with you. The IMF site seems to have recently fleshed out the details of the BSI. They specifically mentioned my doctor, Ola Landgren, in the FAQ's section. he is on the BSI committee. I am going to ask him about it next week when I go to clinic at the NIH.
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terryl1 - Name: Terry
- Who do you know with myeloma?: self
- When were you/they diagnosed?: August 10, 2011
- Age at diagnosis: 49
Re: Allo transplant cures?
terryl1 wrote:
> Hi Multibilly, I agree with you. The IMF site seems to have recently
> fleshed out the details of the BSI. They specifically mentioned my doctor,
> Ola Landgren, in the FAQ's section. he is on the BSI committee. I am going
> to ask him about it next week when I go to clinic at the NIH.
Thanks Terry. I've read some articles by/about Dr. Landgren. Seems like he is a brilliant doc and I look forward to any news you might be able to share.
> Hi Multibilly, I agree with you. The IMF site seems to have recently
> fleshed out the details of the BSI. They specifically mentioned my doctor,
> Ola Landgren, in the FAQ's section. he is on the BSI committee. I am going
> to ask him about it next week when I go to clinic at the NIH.
Thanks Terry. I've read some articles by/about Dr. Landgren. Seems like he is a brilliant doc and I look forward to any news you might be able to share.
-
Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Allo transplant cures?
Hi Multibilly, He's honestly one of the best persons I have met in my life. I know many of his patients feel the same. Hopefully, I will see him next week and I will ask him about it.
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terryl1 - Name: Terry
- Who do you know with myeloma?: self
- When were you/they diagnosed?: August 10, 2011
- Age at diagnosis: 49
Re: Allo transplant cures?
Multibilly wrote:
> LibbyC wrote:
> > Hi Dee777,
> > Cure vs control. Would anyone who has/had myeloma actually believe their
> > doctor if they say you are "cured". My first question would be
> > "how do you know? to be followed with "what proof do you have?
>
> Call me an optimist, but I would believe my doctor if he said I was cured if I had in
> fact gone through a series of targeted therapies and had a series of molecular
> response tests that showed absolutely zero MRD. I'm actually quite surprised that the
> Black Swan Initiative hasn't generated more discussion on this site and that more
> details (and news in general regarding multiple myeloma treatments) weren't
> forthcoming out of the IMW 2013
Allow me to correct my earlier assertion. After LibbyC communicated with me a bit more regarding the current limitations of molecular testing, I agree that one cannot currently really know if they have been cured or not. There simply is no way to test for all the possible molecular variations that may have caused multiple myeloma in the first place, or that had developed during the course of the disease. But can one get closer to having a "cleaner multiple myeloma bill of health" with what the Black Swan Initiative and other groups are envisioning? I think so...and certainly hope so.
> LibbyC wrote:
> > Hi Dee777,
> > Cure vs control. Would anyone who has/had myeloma actually believe their
> > doctor if they say you are "cured". My first question would be
> > "how do you know? to be followed with "what proof do you have?
>
> Call me an optimist, but I would believe my doctor if he said I was cured if I had in
> fact gone through a series of targeted therapies and had a series of molecular
> response tests that showed absolutely zero MRD. I'm actually quite surprised that the
> Black Swan Initiative hasn't generated more discussion on this site and that more
> details (and news in general regarding multiple myeloma treatments) weren't
> forthcoming out of the IMW 2013
Allow me to correct my earlier assertion. After LibbyC communicated with me a bit more regarding the current limitations of molecular testing, I agree that one cannot currently really know if they have been cured or not. There simply is no way to test for all the possible molecular variations that may have caused multiple myeloma in the first place, or that had developed during the course of the disease. But can one get closer to having a "cleaner multiple myeloma bill of health" with what the Black Swan Initiative and other groups are envisioning? I think so...and certainly hope so.
-
Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Allo transplant cures?
Hi Multibilly,
The best paper I have read on testing in myeloma is this one by Dr. Guido Tricot. If interested you should read the PDF version because the graphs are readable. I could not attach the link to the PDF version for some reason. The title is "What is the significance of molecular remission in multiple myeloma?" if this link does not open.
http://webcache.googleusercontent.com/search?q=cache:27CfuIMLeAYJ:www.researchgate.net/publication/6461694_What_is_the_significance_of_molecular_remission_in_multiple_myeloma/file/d912f5122294a71679.pdf+What+is+the+significance+of+molecular+remission+in+multiple+myeloma%3F&cd=3&hl=en&ct=clnk&gl=us
A molecular response using the most sensitive testing techniques we currently use is not a guarantee of a cure but loss of a sustained molecular response after allo transplant is rare. Here is study from 2003 that shows this.
"Using polymerase chain reaction (PCR) for immunoglobulin gene rearrangements it was possible to generate a clone-specific molecular marker in 48 of 70 patients. Of these 48 patients, 16 (33%) attained durable PCR-negativity after transplantation, whereas 13 (27%) remained persistently PCR-positive and 19 (40%) showed a mixed pattern. The cumulative risk of relapse at 5 years was 0% for PCR-negative patients, 33% for PCR-mixed patients, and 100% for PCR-positive patients. Within the group studied it was not possible to identify any clinical feature predictive of durable PCR-negativity. "
But......
"The attainment of persistent PCR-negativity has a favorable impact, but it is not synonymous of cure, since we observed a patient relapsing after 9 years of molecular remission (Figure 1B). The escape from the immunologic control of a residual myeloma clone can perhaps explain the occurrence of very late relapses."
http://bloodjournal.hematologylibrary.org/content/102/5/1927.full
In the non-allo setting patients do not get the benefit of the immunotherapy of the donor immune system so relapse is much more common. This was mentioned in a recent paper by Dr. Antonio Palumbo.
"However, even in patients with stringent, immunophenotypic, or molecular CR, late relapses occur, showing the need for adequate biomarkers to detect the eradication of the tumor clone in vivo. In a recent analysis, after a median follow-up of 65 months, the 6-year PFS was 46%, despite the previous achievement of a molecular CR. It is important not only to achieve CR but also to maintain a sustained CR. Patients with sustained CR for ≥ 3 years had a longer OS than patients who had unsustained CR (5-year OS, 82% vs 24%; P < .001).9 These data support a treatment strategy tailored to increase both CR rates and duration of response."
http://asheducationbook.hematologylibrary.org/content/2012/1/335.long
The real world application of this data is in making treatment decisions. I have sustained a molecular response for 2 years since my allo so I do not treat. It spares me of the side effects of long cycIes of proteasome inhibitors and IMIDs. It is good to base your treatment decisions on outcomes of long term studies and the best testing techniques and not just your Doctors opinion.
Mark
The best paper I have read on testing in myeloma is this one by Dr. Guido Tricot. If interested you should read the PDF version because the graphs are readable. I could not attach the link to the PDF version for some reason. The title is "What is the significance of molecular remission in multiple myeloma?" if this link does not open.
http://webcache.googleusercontent.com/search?q=cache:27CfuIMLeAYJ:www.researchgate.net/publication/6461694_What_is_the_significance_of_molecular_remission_in_multiple_myeloma/file/d912f5122294a71679.pdf+What+is+the+significance+of+molecular+remission+in+multiple+myeloma%3F&cd=3&hl=en&ct=clnk&gl=us
A molecular response using the most sensitive testing techniques we currently use is not a guarantee of a cure but loss of a sustained molecular response after allo transplant is rare. Here is study from 2003 that shows this.
"Using polymerase chain reaction (PCR) for immunoglobulin gene rearrangements it was possible to generate a clone-specific molecular marker in 48 of 70 patients. Of these 48 patients, 16 (33%) attained durable PCR-negativity after transplantation, whereas 13 (27%) remained persistently PCR-positive and 19 (40%) showed a mixed pattern. The cumulative risk of relapse at 5 years was 0% for PCR-negative patients, 33% for PCR-mixed patients, and 100% for PCR-positive patients. Within the group studied it was not possible to identify any clinical feature predictive of durable PCR-negativity. "
But......
"The attainment of persistent PCR-negativity has a favorable impact, but it is not synonymous of cure, since we observed a patient relapsing after 9 years of molecular remission (Figure 1B). The escape from the immunologic control of a residual myeloma clone can perhaps explain the occurrence of very late relapses."
http://bloodjournal.hematologylibrary.org/content/102/5/1927.full
In the non-allo setting patients do not get the benefit of the immunotherapy of the donor immune system so relapse is much more common. This was mentioned in a recent paper by Dr. Antonio Palumbo.
"However, even in patients with stringent, immunophenotypic, or molecular CR, late relapses occur, showing the need for adequate biomarkers to detect the eradication of the tumor clone in vivo. In a recent analysis, after a median follow-up of 65 months, the 6-year PFS was 46%, despite the previous achievement of a molecular CR. It is important not only to achieve CR but also to maintain a sustained CR. Patients with sustained CR for ≥ 3 years had a longer OS than patients who had unsustained CR (5-year OS, 82% vs 24%; P < .001).9 These data support a treatment strategy tailored to increase both CR rates and duration of response."
http://asheducationbook.hematologylibrary.org/content/2012/1/335.long
The real world application of this data is in making treatment decisions. I have sustained a molecular response for 2 years since my allo so I do not treat. It spares me of the side effects of long cycIes of proteasome inhibitors and IMIDs. It is good to base your treatment decisions on outcomes of long term studies and the best testing techniques and not just your Doctors opinion.
Mark
-
Mark
Re: Allo transplant cures?
Cure, what an interesting concept! What is cure. Is cure when you no longer have any myeloma cells in you body, but then some people have MGUS or Smoldering Myeloma with myeloma cells and never have any CRAB involvement and die of old age, never having experience any of the ravages of this disease. Some may have gone though treatment and are in CR with no MRD(minimum residual disease) but the CRAB involvement has ravaged their body and they die of heart failure, kidney failure, pneumonia, or some other pathogen. Were they cured? Some analysis would say that the SCT has a way to hit a reset of the bodies biology and can provide an average life expectancy greater than that of the average non myeloma person of the same age. So is allo a cure, maybe, if the current TRM(treatment related mortality) is less than the 35 to 50% that used to be quoted, and the average allo patient live as long or longer than the average person of the same age without myeloma. I do not know what the new number is for TRM, although I have heard some great hearsay from people treated at Moffitt that it is much, much, much, less now.
So you bring up a great question. I am in CR and have been for 7 years. However, my body took a heck of a lick from the disease at diagnosis, kidney damage, and I would say the heavy chains probably did a job on my heart, lungs, brain, and other organs as well. So I am now 63, and the average american at age 63 will live an average of 18.66 years more. So if I make it to 81.66 year old or more, I will feel like I was not cheated out of LIFE by multiple myeloma, and if I don't make it to 82, I am going to blame the &%$# MYELOMA!
Best Regards and God Bless your myeloma journey/Gary
So you bring up a great question. I am in CR and have been for 7 years. However, my body took a heck of a lick from the disease at diagnosis, kidney damage, and I would say the heavy chains probably did a job on my heart, lungs, brain, and other organs as well. So I am now 63, and the average american at age 63 will live an average of 18.66 years more. So if I make it to 81.66 year old or more, I will feel like I was not cheated out of LIFE by multiple myeloma, and if I don't make it to 82, I am going to blame the &%$# MYELOMA!
Best Regards and God Bless your myeloma journey/Gary
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Gary P
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