I referenced the wrong blog in connection with Gonzales: It is actually "Curing Myeloma," and here is her link:
http://curingmyeloma.blogspot.com/2012/02/test-results.html
Gonzales is not without controversy -- which is part of the reason I enjoy reading about him. It is not black and white.
Forums
Re: carfilzomib responses comparable to BST says Jakubowiak
Hey Kevin,
you write:
"With a stem cell transplant, you also work to beat back the cancerous M-proteins, but then collect stems cells, take heavy-duty chemo to kill off the remaing stem cells, then reintroduce the collected stem cells. In this case, you've effectively killed off a bunch of the stem cells in addition to the M-proteins, and theoretically, the only cancerous stem cells should be those reintroduced into your system by the transplant. Consequently, it seems like it would take a lot longer to reach critical mass again."
I agree.
Here's the thing I see. While the stem cell is the target that is producing the monoclonal proteins which are not useful, no therapy we have presently attacks that. Not even BSCT. The actual therapy during BSCT is the hi-dose chemo. Where they basically scorch your marrow. Your stem cells are not treated and they give you back your same diseased cells to rescue you after taking you to the brink with the highly toxic melphalan. The big difference is how long before it reaches critical mass again, as you note.
Individuals have to decide if they want to endure that toxicity, since the BST process is grueling, the recovery can be very problematic and the immune system is so fragile.
I am not convinced that BSCT is a good alternative long term...despite the OS increases we see in studies. Simply because so many folks have enduring issues post BST. However, I recognize that it is a deeply personal decision.
you also write:
"One of the things on my myeloma to-do list is a bit of research into the progression free response of RVD and other combination treatments to see how they compare with stem cell transplants, then try and extrapolate this to CRD."
When we look at these two combos, you would actually be comparing V vs.C. C of course has no where near the length of therapy as V does. What we do know from studies with continuing V is that patients are having PFS comparable to BSCT just as Jakobowiak is speculating we will see with C.
Based on the data with bortezomib we have good reason to believe that C will have similiar if not better outcomes. The reason being that bortezomib is a reversible proteasome inhibitor vs. carfilzomib being an irreversible inhibitor. That means in terms of resistance the cells cannot just build up a higher concentration and overcome carfilzomib as they can with bortezomib. New proteasomes have to be manufactured due to the irreversible inhibition.
There is data already supporting how bortezomib is comparable to BSCT:
http://www.ncbi.nlm.nih.gov/pubmed/19031743
And there is a new trial recruiting which is designed to compare BSCT vs. RVD
http://clinicaltrials.gov/ct2/show/NCT01208662
you write:
"With a stem cell transplant, you also work to beat back the cancerous M-proteins, but then collect stems cells, take heavy-duty chemo to kill off the remaing stem cells, then reintroduce the collected stem cells. In this case, you've effectively killed off a bunch of the stem cells in addition to the M-proteins, and theoretically, the only cancerous stem cells should be those reintroduced into your system by the transplant. Consequently, it seems like it would take a lot longer to reach critical mass again."
I agree.
Here's the thing I see. While the stem cell is the target that is producing the monoclonal proteins which are not useful, no therapy we have presently attacks that. Not even BSCT. The actual therapy during BSCT is the hi-dose chemo. Where they basically scorch your marrow. Your stem cells are not treated and they give you back your same diseased cells to rescue you after taking you to the brink with the highly toxic melphalan. The big difference is how long before it reaches critical mass again, as you note.
Individuals have to decide if they want to endure that toxicity, since the BST process is grueling, the recovery can be very problematic and the immune system is so fragile.
I am not convinced that BSCT is a good alternative long term...despite the OS increases we see in studies. Simply because so many folks have enduring issues post BST. However, I recognize that it is a deeply personal decision.
you also write:
"One of the things on my myeloma to-do list is a bit of research into the progression free response of RVD and other combination treatments to see how they compare with stem cell transplants, then try and extrapolate this to CRD."
When we look at these two combos, you would actually be comparing V vs.C. C of course has no where near the length of therapy as V does. What we do know from studies with continuing V is that patients are having PFS comparable to BSCT just as Jakobowiak is speculating we will see with C.
Based on the data with bortezomib we have good reason to believe that C will have similiar if not better outcomes. The reason being that bortezomib is a reversible proteasome inhibitor vs. carfilzomib being an irreversible inhibitor. That means in terms of resistance the cells cannot just build up a higher concentration and overcome carfilzomib as they can with bortezomib. New proteasomes have to be manufactured due to the irreversible inhibition.
There is data already supporting how bortezomib is comparable to BSCT:
http://www.ncbi.nlm.nih.gov/pubmed/19031743
And there is a new trial recruiting which is designed to compare BSCT vs. RVD
http://clinicaltrials.gov/ct2/show/NCT01208662
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: carfilzomib responses comparable to BST says Jakubowiak
Hi Dan!
You write:
"Why does James Berenson, whose treatments offer among the longest and highest quality survival, absolutely counsel NOT to do it - unless as a last resort? He properly views this disease as a marathon, where chronic disease management should be a priority. We should all be looking more closely at his approach -- where less is more. "
I too look at multiple myeloma as possibly being a chronic disease, that we will manage like diabetes.
I like Berenson's philosophy and also believe it is the best long-term strategy. I have not been successful however in finding any audio/visual materials, articles, presentations where he explains the rationale for his beliefs. Have you?
You write:
"Why does James Berenson, whose treatments offer among the longest and highest quality survival, absolutely counsel NOT to do it - unless as a last resort? He properly views this disease as a marathon, where chronic disease management should be a priority. We should all be looking more closely at his approach -- where less is more. "
I too look at multiple myeloma as possibly being a chronic disease, that we will manage like diabetes.
I like Berenson's philosophy and also believe it is the best long-term strategy. I have not been successful however in finding any audio/visual materials, articles, presentations where he explains the rationale for his beliefs. Have you?
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: carfilzomib responses comparable to BST says Jakubowiak
Hi Nancy!
You asked:
"I wonder if the FDA would be asked to consider this drug for initially diagnosed as well as relapsed patients?"
Both Kevin and I are newly diagnosed patients participating in a clinical trial (different sites) designed for that very purpose. The data from these trials treating newly diagnosed patients will be submitted to the FDA by Onyx for them to get an indication for the newly diagnosed patient. Data for relapsed/refractory patients has been completed.
You asked:
"I wonder if the FDA would be asked to consider this drug for initially diagnosed as well as relapsed patients?"
Both Kevin and I are newly diagnosed patients participating in a clinical trial (different sites) designed for that very purpose. The data from these trials treating newly diagnosed patients will be submitted to the FDA by Onyx for them to get an indication for the newly diagnosed patient. Data for relapsed/refractory patients has been completed.
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: carfilzomib responses comparable to BST says Jakubowiak
Hi Suzierose...that explains what I was wondering. I know that you and Kevin are both recently diagnosed, and didn't realize that you were in a separate trial from the 'relapsed' patients. I have a lot to learn in the area of cancer drugs!! Hopefully you and the other patients will experience the same success as Kevin, too. Am wishing you all the best for that!
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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: carfilzomib responses comparable to BST says Jakubowiak
Hi Suzierose,
As you know, I am a patient of Dr. Landgren's in his natural history study of myeloma and its precursor stages. I am closely monitored by him as he considers me to be at high risk for progression. So far, pursuant to the CRAB criteria, my calcium is ok (I have very high albumin which he thinks may be protecting me somewhat--about 4.8 to 5.0), my renal function is normal, my hemoglobin is about 12.0 and my imaging studies were clean. However, my PC infiltration is high--over 60%--maybe they hit a pocket??? Anyway, if you know, who on the east coast is a proponent of Dr. Berenson vis-a-vis SCT's and his philosophy not to do them? I get the feeling Dr. Landgren is not so keen but I never asked him. I am also monitored at UPenn which is top notch and I like my doctor there a lot. He firmly believes in stem cell transplantation and has had great success with them. Therein lies the rub for the future...what to do when so much rides on this decision--can I work again, wife, young kids, etc. On this very site, I have read about great successes with SCT's and yet there are others who regret the decision and have seen their situation worsen. Thanks for letting me know if there is a Dr. Berenson type of multiple myeloma expert on the east coast. Thanks. Terry
As you know, I am a patient of Dr. Landgren's in his natural history study of myeloma and its precursor stages. I am closely monitored by him as he considers me to be at high risk for progression. So far, pursuant to the CRAB criteria, my calcium is ok (I have very high albumin which he thinks may be protecting me somewhat--about 4.8 to 5.0), my renal function is normal, my hemoglobin is about 12.0 and my imaging studies were clean. However, my PC infiltration is high--over 60%--maybe they hit a pocket??? Anyway, if you know, who on the east coast is a proponent of Dr. Berenson vis-a-vis SCT's and his philosophy not to do them? I get the feeling Dr. Landgren is not so keen but I never asked him. I am also monitored at UPenn which is top notch and I like my doctor there a lot. He firmly believes in stem cell transplantation and has had great success with them. Therein lies the rub for the future...what to do when so much rides on this decision--can I work again, wife, young kids, etc. On this very site, I have read about great successes with SCT's and yet there are others who regret the decision and have seen their situation worsen. Thanks for letting me know if there is a Dr. Berenson type of multiple myeloma expert on the east coast. Thanks. Terry
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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: Berenson
To Suzie Rose et al.
The following link -- although not as sophisticated as we scientists might like -- includes a number of video interviews with Berenson that touch upon numerous issues, including stem cell transplants, and more generally, the shift to the marathon versus sprint approach to treatment:
http://www.oncologytube.com
By the way, Berenson will readily acknowledge that in some cases, an ASCT does have tremendous results -- but such cases are in the vast minority. And they are counterbalanced by miserable failures that exaccerbate the disease. We should all be asking our doctors what the typical result is -- not the rare exeception -- and get a sense of the prognostic indicators of likely success. My oncologist recently suggested four cycles of VRD followed immediately by an ASCT to get a deep and long remission. Sound great -- IF IT WORKS.
If I do face an ASCT, I would rather do it down the road when it will likely be combined with immunomodulatory approaches currently under investigations -- such as repopulating the bone marrow with new stem cells PLUS say engineered T-cells. Such combinations may actually offer pro-active long-term control.
Time means everything in this era of rapidly changing treatments and disease insights, and as far as I am concerned, the longer one can hold off, the better. At this point, I have seen NO convincing evidence that in the new era of drugs, there is any significant difference between immediate and delayed transplant. I think you allude to the exact same: So why nuke my bone marrow and its "soil" if I don't have to?
The following link -- although not as sophisticated as we scientists might like -- includes a number of video interviews with Berenson that touch upon numerous issues, including stem cell transplants, and more generally, the shift to the marathon versus sprint approach to treatment:
http://www.oncologytube.com
By the way, Berenson will readily acknowledge that in some cases, an ASCT does have tremendous results -- but such cases are in the vast minority. And they are counterbalanced by miserable failures that exaccerbate the disease. We should all be asking our doctors what the typical result is -- not the rare exeception -- and get a sense of the prognostic indicators of likely success. My oncologist recently suggested four cycles of VRD followed immediately by an ASCT to get a deep and long remission. Sound great -- IF IT WORKS.
If I do face an ASCT, I would rather do it down the road when it will likely be combined with immunomodulatory approaches currently under investigations -- such as repopulating the bone marrow with new stem cells PLUS say engineered T-cells. Such combinations may actually offer pro-active long-term control.
Time means everything in this era of rapidly changing treatments and disease insights, and as far as I am concerned, the longer one can hold off, the better. At this point, I have seen NO convincing evidence that in the new era of drugs, there is any significant difference between immediate and delayed transplant. I think you allude to the exact same: So why nuke my bone marrow and its "soil" if I don't have to?
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Dan D
Re: carfilzomib responses comparable to BST says Jakubowiak
Hey Terry!!
I was trying to think of who might have been on East Coast when you asked about Berenson. I honestly do not know. I think it is something that likely has to be asked around amoungst the multiple myeloma docs. I have the impression that Mayo Clinic and Landgren both know that BSCT is the 'standard of care" but I also have the impression that both view that therapeutic route as not providing QOL and no study has shown increased survival with BSCT.
Consequently, those two are conservatively cautious and far less less likely to be proponents despite understanding it is the 'standard of care'.
I told my friend the other day, America has quality health care but it is getting the best quality health care that can be challengeing. BSCT fits into that paradigm.
I was trying to think of who might have been on East Coast when you asked about Berenson. I honestly do not know. I think it is something that likely has to be asked around amoungst the multiple myeloma docs. I have the impression that Mayo Clinic and Landgren both know that BSCT is the 'standard of care" but I also have the impression that both view that therapeutic route as not providing QOL and no study has shown increased survival with BSCT.
Consequently, those two are conservatively cautious and far less less likely to be proponents despite understanding it is the 'standard of care'.
I told my friend the other day, America has quality health care but it is getting the best quality health care that can be challengeing. BSCT fits into that paradigm.
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: carfilzomib responses comparable to BST says Jakubowiak
Hi Dan!
I agree you do have to read between the lines and ask 'the right' questions a lot of times to truly get a in depth response that allows you the patient to make an informed decision about your life and therapy.
For instance:
"However, two recent studies have shown that if you compare the newer drugs to transplantation, that transplantation is still superior. This was shown in the Italian study by Palumbo and colleagues; it was also shown in a recent study by Jakubowiak, et al., in Blood showing that patients who do not have a transplant have a much shorter complete remission duration. Therefore, transplantation remains an essential part of the treatment of patients with multiple myeloma as long as they are candidates for transplantation. "
Boccador M, et al. J Clin Oncol. 2011;29: (suppl. Abstr 8020).
Jakubowiak, AJ, et al. Blood. 2011;118(3):535-543.
Based on the above studies you come away believing transplantation is definitely an excellent choice, unless you know that longer remission is NOT increased survival. The verbage used in trials can be somewhat misleading unless you pay close attention to the criteria that are specifically being stated to be superior. And you would have the impression that Jakubowiak is contradicting himself when he is not.
If the goal is complete remission and long term management and that is achieved withOUT the transplant, why would an individual want to pursue ASCT?
Moreover, as you noted, ASCT doesn't work in the vast majority of cases as the individual fails to achieve a CR. So, it is a lot for the individual to weigh when it comes to the risks and benefits. Personally, I am not in the group where the prognosis is positive for a BSCT. Even before I learned of my cytogenetic profile however, I had serious questions about BSCT. I simply am unable to wrap my head around the entire concept medically. It sounds like a desperate measure that was conceived of by a 'cutting edge' physician and may have been lauded at the time. I think there are better measures today with far less toxicity and the overall survival has not changed. My bottom line question is why should I undergo a procedure that has not improved survival in over 40 years? Sure it will put me in remission but remission is not survival. And the remission will have less QOL due to the grueling procedure. However, I would never advise anyone about their individual choice. Each person has to make their own and be willing to endure the outcomes. I found Killingsworth blog on this issue very interesting in that regard.
I tried your link, but Berenson did not come up. I have seen him interviewed a few times at ASH as well as on PatientPower ASCO 2011...while he is clear about ASCT not being first choice, he doesn't really specify scientifically his reasons. Now, of course I can guess, but I really want to hear his thinking.
I beleive there is a subset of multiple myeloma where ASCT works exceptionally well, but a patient has to know where they fit on that spectrum to make an truly informed decision. Afterall, one of the biggest misconceptions is that the stem cell 'transplant' is the therapy, when actually it is the high dose chemo that is the therapy. You are only given back your own stem cells because you would die otherwise as the hi-dose chemo has wiped your stem cells out. But your own stem cells are not some new&improved version...they are the same ones you had to begin with.
I agree you do have to read between the lines and ask 'the right' questions a lot of times to truly get a in depth response that allows you the patient to make an informed decision about your life and therapy.
For instance:
"However, two recent studies have shown that if you compare the newer drugs to transplantation, that transplantation is still superior. This was shown in the Italian study by Palumbo and colleagues; it was also shown in a recent study by Jakubowiak, et al., in Blood showing that patients who do not have a transplant have a much shorter complete remission duration. Therefore, transplantation remains an essential part of the treatment of patients with multiple myeloma as long as they are candidates for transplantation. "
Boccador M, et al. J Clin Oncol. 2011;29: (suppl. Abstr 8020).
Jakubowiak, AJ, et al. Blood. 2011;118(3):535-543.
Based on the above studies you come away believing transplantation is definitely an excellent choice, unless you know that longer remission is NOT increased survival. The verbage used in trials can be somewhat misleading unless you pay close attention to the criteria that are specifically being stated to be superior. And you would have the impression that Jakubowiak is contradicting himself when he is not.
If the goal is complete remission and long term management and that is achieved withOUT the transplant, why would an individual want to pursue ASCT?
Moreover, as you noted, ASCT doesn't work in the vast majority of cases as the individual fails to achieve a CR. So, it is a lot for the individual to weigh when it comes to the risks and benefits. Personally, I am not in the group where the prognosis is positive for a BSCT. Even before I learned of my cytogenetic profile however, I had serious questions about BSCT. I simply am unable to wrap my head around the entire concept medically. It sounds like a desperate measure that was conceived of by a 'cutting edge' physician and may have been lauded at the time. I think there are better measures today with far less toxicity and the overall survival has not changed. My bottom line question is why should I undergo a procedure that has not improved survival in over 40 years? Sure it will put me in remission but remission is not survival. And the remission will have less QOL due to the grueling procedure. However, I would never advise anyone about their individual choice. Each person has to make their own and be willing to endure the outcomes. I found Killingsworth blog on this issue very interesting in that regard.
I tried your link, but Berenson did not come up. I have seen him interviewed a few times at ASH as well as on PatientPower ASCO 2011...while he is clear about ASCT not being first choice, he doesn't really specify scientifically his reasons. Now, of course I can guess, but I really want to hear his thinking.
I beleive there is a subset of multiple myeloma where ASCT works exceptionally well, but a patient has to know where they fit on that spectrum to make an truly informed decision. Afterall, one of the biggest misconceptions is that the stem cell 'transplant' is the therapy, when actually it is the high dose chemo that is the therapy. You are only given back your own stem cells because you would die otherwise as the hi-dose chemo has wiped your stem cells out. But your own stem cells are not some new&improved version...they are the same ones you had to begin with.
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: carfilzomib responses comparable to BST says Jakubowiak
Nancy
Currently at the NIH Dr. Landgren and his team are doing a Trial for Newly diagnosed patients with Carfilzomib,Rev and Dex. They also told me they will be doing the same trial for Smoldering patients in the Spring as well. Maybe this research will help to support an approval by the FDA for newly diagnosed.??? Something to think about for sure. It is an intensive therapy though. Two days a week, Three weeks a month for 8 months. With a break after 4 cycles for stem cell collection. But not with the intention of using them as part of the study. but for later use outside of the trial.
Currently at the NIH Dr. Landgren and his team are doing a Trial for Newly diagnosed patients with Carfilzomib,Rev and Dex. They also told me they will be doing the same trial for Smoldering patients in the Spring as well. Maybe this research will help to support an approval by the FDA for newly diagnosed.??? Something to think about for sure. It is an intensive therapy though. Two days a week, Three weeks a month for 8 months. With a break after 4 cycles for stem cell collection. But not with the intention of using them as part of the study. but for later use outside of the trial.
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Art - Name: Art
- Who do you know with myeloma?: Self
- When were you/they diagnosed?: 12/2011
- Age at diagnosis: 40
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