Hi DanD
I agree.
The stem cell is analogous to the root of a weed.You can cut off the top all you want. Until you eradicate (pull up) the root ..the weed will continue to grow back.
At present, PFS only equals the length of the time for the weed to re-grow. If therapy is toxic enough re growth takes longer, but it is not eradicated.
Relapse is inevitable.
Forums
Re: Berenson 5 Year OS Data Superior to UAMS
Suzierose,
I agree with your post except for one point.
I don't agree with the statement that "relapse is inevitable".
As I indicated in my previous post, individuals that have achieved a CR, either through VRD combination therapy or through ASCT, can potentially stay in remission indefinitely through maintenance with a combination protocol, such as VRD with aredia or zometra. The analogy is HIV. When new agents were first used against HIV it was done as single agent therapy. HIV, being a virus, mutates very rapidly, and built resistance to the single agents used against it.
The current practice is to use multiple agents against HIV in a cocktail. That has proven to be very effective and HIV has not built up resistance thus far. In a similar way we have seen multiple myeloma build up a resistance to single agents such as Revlimid or Velcade. However, when used in combination the resistance has been slowed even halted in some cases. Thus a maintenance program using VRD plus one of the bisphosphonates offers the possibility of indefinite remission. With new agents being developed the cocktail can be altered or enhanced. This is not a cure but offers hope for long sustainable remission without the inevitable relapse.
Ron
I agree with your post except for one point.
I don't agree with the statement that "relapse is inevitable".
As I indicated in my previous post, individuals that have achieved a CR, either through VRD combination therapy or through ASCT, can potentially stay in remission indefinitely through maintenance with a combination protocol, such as VRD with aredia or zometra. The analogy is HIV. When new agents were first used against HIV it was done as single agent therapy. HIV, being a virus, mutates very rapidly, and built resistance to the single agents used against it.
The current practice is to use multiple agents against HIV in a cocktail. That has proven to be very effective and HIV has not built up resistance thus far. In a similar way we have seen multiple myeloma build up a resistance to single agents such as Revlimid or Velcade. However, when used in combination the resistance has been slowed even halted in some cases. Thus a maintenance program using VRD plus one of the bisphosphonates offers the possibility of indefinite remission. With new agents being developed the cocktail can be altered or enhanced. This is not a cure but offers hope for long sustainable remission without the inevitable relapse.
Ron
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Ron Harvot - Name: Ron Harvot
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: Feb 2009
- Age at diagnosis: 56
Re: Berenson 5 Year OS Data Superior to UAMS
Ron, thanks for the clear explanation. That seems to back up the importance of the maintenance regimen UAMS practices, where a combination of the agents, rather than a single agent, are used. Patiens do receive higher toxicity, but the benefits are greater as well, with the potential of preventing the disease from coming back for a long time.
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Ben S.
Re: Berenson 5 Year OS Data Superior to UAMS
Ben,
I am one of the patients that did induction with VRD plus Aredia and had a CR. I am still on VRD and Aredia but my Velcade infusions have been moved to once every 2 weeks from once a week. My Dex was cut from 40 mg every week to 20 mg every other week. The Aredia was cut from once a month to once every 2 months. I have been taking 10 mg of Revlimid (On 21days off 7days) since I was diagnosed back in Feb. 2009. I have been in remission going on 3 years and never had an ASCT. I am an avid cyclist doing over 4,800 miles this past year and plan on competing in the Texas Senior Olympics in 4 different cycling events (trying to qualify for the nationals). Adopting a regime of exercise and goals setting, helps with fighting the disease both mentally and physically IMO.
The VRD maintenance protocol is trial and error and has to be tailored to each individual. I am fortunate, compared to many others, in that I have not had any serious side effects from the treatments. The only thing that bothers me is the dex and it is not that bad. I have maintained my employment since being diagnosed and am not limited in any material way.
If I did not have a CR with the VRD, I would have probably turned to ASCT. However, since I did have a CR, I decided after consulting with my oncologist, that ASCT was not really going to improve my response but did present potential risk. Furthermore, I would have been on a maintenance therapy that is similar to what I am doing anyway.
Ron
I am one of the patients that did induction with VRD plus Aredia and had a CR. I am still on VRD and Aredia but my Velcade infusions have been moved to once every 2 weeks from once a week. My Dex was cut from 40 mg every week to 20 mg every other week. The Aredia was cut from once a month to once every 2 months. I have been taking 10 mg of Revlimid (On 21days off 7days) since I was diagnosed back in Feb. 2009. I have been in remission going on 3 years and never had an ASCT. I am an avid cyclist doing over 4,800 miles this past year and plan on competing in the Texas Senior Olympics in 4 different cycling events (trying to qualify for the nationals). Adopting a regime of exercise and goals setting, helps with fighting the disease both mentally and physically IMO.
The VRD maintenance protocol is trial and error and has to be tailored to each individual. I am fortunate, compared to many others, in that I have not had any serious side effects from the treatments. The only thing that bothers me is the dex and it is not that bad. I have maintained my employment since being diagnosed and am not limited in any material way.
If I did not have a CR with the VRD, I would have probably turned to ASCT. However, since I did have a CR, I decided after consulting with my oncologist, that ASCT was not really going to improve my response but did present potential risk. Furthermore, I would have been on a maintenance therapy that is similar to what I am doing anyway.
Ron
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Anonymous
Re: Berenson 5 Year OS Data Superior to UAMS
Ron:
That makes a lot of sense. I am glad that you are doing terrific. Good luck with your cycling competition!
Ben
That makes a lot of sense. I am glad that you are doing terrific. Good luck with your cycling competition!
Ben
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Ben S.
Re: Berenson 5 Year OS Data Superior to UAMS
Here is the way I look at the numbers.
Because multiple myeloma primarily effects older people (average age of onset is 70) there will be a significant number of patients over the age of 80 who, due to age, will have limited options when it comes to treatment. A large number in this group will be treated by their local oncologist. Their OS numbers will be less because of factors like peripheral neuropathy that will prevent them from using novel agents.
Younger patients will have a far greater number of treatment options, are eligiable for stem cell transplants and are far more likely to select a major cancer treatment center. They are also more likely to research the various approaches and make an informed decision on what treatment options are best for them. Those who get treated at major cancer centers are more likely to have good insurance, giving them access to care that the less affluent people with multiple myeloma do not have. Their OS numbers will be better than the total OS numbers of the entire multiple myeloma population.
The decisive factor is not whether Berenson's approach is better than Barlougie's. It is that both centers are far more likely to attract younger, better informed patients with good insurance.
Study the various approaches to multiple myeloma. Choose the approach that is best FOR YOU. You have options.
Because multiple myeloma primarily effects older people (average age of onset is 70) there will be a significant number of patients over the age of 80 who, due to age, will have limited options when it comes to treatment. A large number in this group will be treated by their local oncologist. Their OS numbers will be less because of factors like peripheral neuropathy that will prevent them from using novel agents.
Younger patients will have a far greater number of treatment options, are eligiable for stem cell transplants and are far more likely to select a major cancer treatment center. They are also more likely to research the various approaches and make an informed decision on what treatment options are best for them. Those who get treated at major cancer centers are more likely to have good insurance, giving them access to care that the less affluent people with multiple myeloma do not have. Their OS numbers will be better than the total OS numbers of the entire multiple myeloma population.
The decisive factor is not whether Berenson's approach is better than Barlougie's. It is that both centers are far more likely to attract younger, better informed patients with good insurance.
Study the various approaches to multiple myeloma. Choose the approach that is best FOR YOU. You have options.
-
Matt - Name: Matt Linden
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: April 2009
- Age at diagnosis: 44
Re: Berenson 5 Year OS Data Superior to UAMS
Hi Ron,
If relapse were not inevitable, then multiple myeloma is not incurable, no?
Resistance can be minimized with combination therapy and multiple myeloma patients with out negative cytogenetic profiles can have a longer progression free survival. These patients appear to comprise 75% of what is called conventional multiple myeloma patients. However, even they relapse.
Moreover, we know that even CR is not necessarily a good prognosticator; as many individuals with PR have longer PFS than those who have less sustainable CR. IOW's the later patients relapse prior to the former. Those patients also have significantly worse overall survival.
What we see in multiple myeloma is a spectrum within the patient population who have chronic disease with combo therapy, however they too relapse over time. Or what I actually believe is that their multiple myeloma is caught far earlier in the disease process and is less pathogenic. Less pathogenic equals longer PFS. Novel therapies have extended PFS but it is call PROGRESSION FREE not survival or cured. Many of the clinical tests that are followed in multiple myeloma are surrogate markers, not true reflections of multiple myeloma DNA stem changes. Rather they are indicative of its impact how the defective DNA stem cells are altering the microenvironment based on the other cellular markers we use like B2 microglubin (non-specific for multiple myeloma), M spike ( stem cell gone wild is increasing) free chain and heavy chain loads, etc. All of these markers are indicative of the sequalae of the stem cell DNA changes multiple myeloma is undergoing, not the myeloma stem cell itself. Patients are defined as PFS then, solely because the tests are not sensitive enough to show progression,( weed, is there it just ain't sprouted above ground yet) the best that can be said is that it is undectable based on the surrogate markers that are used. Or to use air surveillance parlance the disease is under the radar.
With regards to how the disease pathogenesis has lots of similarities to AIDS, we already know that the primary driver of AIDS becoming a chronic disease is that patients were treated in the early stages prior to their HIV virus load becoming insurmountable and their T cell level declining to such critical lows that disease progression was inevitable independent of the combination therapies they were treated with. The tumor burden was too high to surmount.
multiple myeloma, in my personal view, is quite analogous in that regard, unfortunately, no one is treating multiple myeloma in it's earliest stages prior to multiple myeloma DNA cellular changes (tumour burden) overwhelming the normal cells. Just as the medical community consensus was to wait to treat AIDS in the 80s. In fact, some would say the medical community when it comes to multiple myeloma is much more conflicted/perplexed/indecisive as they have created multiple categories of multiple myeloma...i.e. MGUS/Smoldering/myeloma and do not treat the disease in the those early stages again waiting/watching until the disease is far advanced. Which again results in relapse being inevitable.
Rather, at present, the staging system ignores the early stages as it is unsymptomatic just as AIDS was. Thus, many newly diagnosed patients have advanced disease, just as they did with AIDS. The commonality of the disease state is they are both lymphocyte diseases, one being Tcell the other Bcell, auto immune diseases. Unlike AIDS therapy, multiple myeloma treatment does not impact stem cells where the DNA changes have occurred, while HAART(despite resistance) effectively kills/reduces the vector virus (HIV) that drives AIDS, preventing infection of new T cells. multiple myeloma is no where near close to having that type of effective therapy. HAART has resulted in a decrease in the morbidity AND mortality of AIDS. multiple myeloma therapy decreases morbidity. multiple myeloma patients have a better QOL as a result.
Further, what we know from the progression of AIDS, the pathogenesis of multiple myeloma involves building a pro multiple myeloma DNA army PRIOR to it becoming symptomatic until it reaches a critical mass and is able to crowd out the normal cells. Individuals can have AIDS for over 5-10 years without knowing it..the same goes for multiple myeloma; think MGUS/smoldering. The initial symptoms are that innocuous and over that time the lymphocyte changes insidiously build a massive army of cells that alter the function of regulatory genes, just as occurs in multiple myeloma. Once those DNA changes are so far along the disease sustains itself independent of therapy and resistance is one of the ways that occurs as it has created a pro DNA to sustain itself. In AIDS it is called latent reservoir, in multiple myeloma it is called Minimal Residual Disease.
Resistance drives relapse. The normal cells no longer have the capacity or numbers to shift the balance of the dysregulated genes, which create the proMM microenvironment as the DNA regulatory genes have loss their function.The microenvironment is not sustainable for normal cells. Just like weeds taking over a garden.
If you prefer war analogies,the best war analogy is Custer's Last Stand, or the US surge in Iraq with drones.
Which brings us full circle to relapse being inevitable.
I am very happy that we have been able to extend PFS though!
That's the best we have at this stage.
Suzierose.
If relapse were not inevitable, then multiple myeloma is not incurable, no?
Resistance can be minimized with combination therapy and multiple myeloma patients with out negative cytogenetic profiles can have a longer progression free survival. These patients appear to comprise 75% of what is called conventional multiple myeloma patients. However, even they relapse.
Moreover, we know that even CR is not necessarily a good prognosticator; as many individuals with PR have longer PFS than those who have less sustainable CR. IOW's the later patients relapse prior to the former. Those patients also have significantly worse overall survival.
What we see in multiple myeloma is a spectrum within the patient population who have chronic disease with combo therapy, however they too relapse over time. Or what I actually believe is that their multiple myeloma is caught far earlier in the disease process and is less pathogenic. Less pathogenic equals longer PFS. Novel therapies have extended PFS but it is call PROGRESSION FREE not survival or cured. Many of the clinical tests that are followed in multiple myeloma are surrogate markers, not true reflections of multiple myeloma DNA stem changes. Rather they are indicative of its impact how the defective DNA stem cells are altering the microenvironment based on the other cellular markers we use like B2 microglubin (non-specific for multiple myeloma), M spike ( stem cell gone wild is increasing) free chain and heavy chain loads, etc. All of these markers are indicative of the sequalae of the stem cell DNA changes multiple myeloma is undergoing, not the myeloma stem cell itself. Patients are defined as PFS then, solely because the tests are not sensitive enough to show progression,( weed, is there it just ain't sprouted above ground yet) the best that can be said is that it is undectable based on the surrogate markers that are used. Or to use air surveillance parlance the disease is under the radar.
With regards to how the disease pathogenesis has lots of similarities to AIDS, we already know that the primary driver of AIDS becoming a chronic disease is that patients were treated in the early stages prior to their HIV virus load becoming insurmountable and their T cell level declining to such critical lows that disease progression was inevitable independent of the combination therapies they were treated with. The tumor burden was too high to surmount.
multiple myeloma, in my personal view, is quite analogous in that regard, unfortunately, no one is treating multiple myeloma in it's earliest stages prior to multiple myeloma DNA cellular changes (tumour burden) overwhelming the normal cells. Just as the medical community consensus was to wait to treat AIDS in the 80s. In fact, some would say the medical community when it comes to multiple myeloma is much more conflicted/perplexed/indecisive as they have created multiple categories of multiple myeloma...i.e. MGUS/Smoldering/myeloma and do not treat the disease in the those early stages again waiting/watching until the disease is far advanced. Which again results in relapse being inevitable.
Rather, at present, the staging system ignores the early stages as it is unsymptomatic just as AIDS was. Thus, many newly diagnosed patients have advanced disease, just as they did with AIDS. The commonality of the disease state is they are both lymphocyte diseases, one being Tcell the other Bcell, auto immune diseases. Unlike AIDS therapy, multiple myeloma treatment does not impact stem cells where the DNA changes have occurred, while HAART(despite resistance) effectively kills/reduces the vector virus (HIV) that drives AIDS, preventing infection of new T cells. multiple myeloma is no where near close to having that type of effective therapy. HAART has resulted in a decrease in the morbidity AND mortality of AIDS. multiple myeloma therapy decreases morbidity. multiple myeloma patients have a better QOL as a result.
Further, what we know from the progression of AIDS, the pathogenesis of multiple myeloma involves building a pro multiple myeloma DNA army PRIOR to it becoming symptomatic until it reaches a critical mass and is able to crowd out the normal cells. Individuals can have AIDS for over 5-10 years without knowing it..the same goes for multiple myeloma; think MGUS/smoldering. The initial symptoms are that innocuous and over that time the lymphocyte changes insidiously build a massive army of cells that alter the function of regulatory genes, just as occurs in multiple myeloma. Once those DNA changes are so far along the disease sustains itself independent of therapy and resistance is one of the ways that occurs as it has created a pro DNA to sustain itself. In AIDS it is called latent reservoir, in multiple myeloma it is called Minimal Residual Disease.
Resistance drives relapse. The normal cells no longer have the capacity or numbers to shift the balance of the dysregulated genes, which create the proMM microenvironment as the DNA regulatory genes have loss their function.The microenvironment is not sustainable for normal cells. Just like weeds taking over a garden.
If you prefer war analogies,the best war analogy is Custer's Last Stand, or the US surge in Iraq with drones.
Which brings us full circle to relapse being inevitable.
I am very happy that we have been able to extend PFS though!
That's the best we have at this stage.
Suzierose.
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Berenson 5 Year OS Data Superior to UAMS
Hi DAN D!!
"I think the bald truth is that you can attempt to eradicate a stem cell recipient's bone marrow as many times as you want, a la Barlogie, but until you can eliminate the pre-myeloma cells (in both the donor cells and the recipient)it seems to me that you will always have to comtemplate maintenance.
As my grandparents use to say:
Say it again while I listen Dan!!
"I think the bald truth is that you can attempt to eradicate a stem cell recipient's bone marrow as many times as you want, a la Barlogie, but until you can eliminate the pre-myeloma cells (in both the donor cells and the recipient)it seems to me that you will always have to comtemplate maintenance.
As my grandparents use to say:
Say it again while I listen Dan!!
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Berenson 5 Year OS Data Superior to UAMS
Hi Ron:
You queried:
"There is an underlying question raised here, are the results of Dr. Berenson's methods as good or better than UAMS ie: using long term combination novel agents vs. double ASCT?"
The traditional/gold standard method of determing this would be a double-blind randomized controlled clinical trial. Which we will never have so it is unanswerable.
Moreover, Barlogie has consistently declined to participate even in a randomized control trial (RCT).
While each individual has to make their own choices based on their lives, family and lifestyles. I prefer effective over aggressive therapy. In that sense, Berenson wins the day.
You queried:
"There is an underlying question raised here, are the results of Dr. Berenson's methods as good or better than UAMS ie: using long term combination novel agents vs. double ASCT?"
The traditional/gold standard method of determing this would be a double-blind randomized controlled clinical trial. Which we will never have so it is unanswerable.
Moreover, Barlogie has consistently declined to participate even in a randomized control trial (RCT).
While each individual has to make their own choices based on their lives, family and lifestyles. I prefer effective over aggressive therapy. In that sense, Berenson wins the day.
-
suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Berenson 5 Year OS Data Superior to UAMS
Hi suzierose,
I always enjoy reading your comments and suggestions here.
Two quick questions. First, can you point to any article that Dr. Barlogie has published, or anything else, that documents that he has refused to participate in randomly controlled clinical trials to test the regimens he advocates?
Second, has Dr. Berenson's approach been subject to any randomly controlled clinical trials to test it? Has he shown any greater willingness to subject them to such testing than Dr. Barlogie?
I know that Dr. Berenson participates in clinical trials, but I'm not sure these are really trials of his "approach."
Many thanks,
Ricardo
I always enjoy reading your comments and suggestions here.
Two quick questions. First, can you point to any article that Dr. Barlogie has published, or anything else, that documents that he has refused to participate in randomly controlled clinical trials to test the regimens he advocates?
Second, has Dr. Berenson's approach been subject to any randomly controlled clinical trials to test it? Has he shown any greater willingness to subject them to such testing than Dr. Barlogie?
I know that Dr. Berenson participates in clinical trials, but I'm not sure these are really trials of his "approach."
Many thanks,
Ricardo
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