The Cure vs. Control debate has become something of a lighting rod, and has resulted in heated discussions in many forums! But in reality it may just be a myeloma patients preference. Just a choice between two excellent treatment alternatives. This is because the outcomes are really exactly the same. WHAT you say?
First and foremost what is the objective for each of these treatment methods? On the side of control, the objective is to be able to provide a treatment plan that provides control of the disease over time. This can be the sequential use of drugs to maintain a manageable level of the disease, with the next available treatment ready for use at relapse. It can also include up front or delayed use of autologous stem cell transplant, with many treatment options available at relapse. The preferred result is to have the patient die of something that is not myeloma related. The objective of cure is usually to provide either an allogeneic transplant or a very aggressive treatment plan that includes most available drugs plus the autologous transplant(maybe dual), consolidation, and maintenance to eliminate the disease or put it back into a MGUS stage. The preferred result is the same, which is to have the patient die of something that is not myeloma related.
There of course is the question of Quality of Life, but isn't this a question of preference. Do you want to go the control route, and have the constant fear of relapse hanging over your head, or do you want to take the up front aggressive treatment with transplant and maintenance drugs for 3 years to achieve cure.
But how can anyone determine success? What is the measure of success? How can you know if an patient has met the definition of "dying from something that is not myeloma related". If a myeloma patient dies from a heart attack, how can anyone know that the myeloma or the myeloma treatments did not have some impact in the outcome. The devils advocate could have a field day on either side of cure or control. So what would be a good surrogate for success. I believe that if a patient outlives the average American of the same age, this would be a fair measurement of success. The average American at age 70 (this is the average age of myeloma patients), will on average live an additional 16 years. This is based on the Social Security Death Rate table. If a 70 year old myeloma patient lives to age 86 then I would say he has met this definition of success. This same analysis can be accomplished for any myeloma patient no matter what the age.
A recent debate on the Forum of the Myeloma Beacon questions the high number of patients that have died from other unknown causes in the Total Therapy 2 (TT2) program which was conducted by the Arkansas UAMS program. It is surmised that because the other unknown causes of death is 29% of the total deaths, that this means that the performance of TT2 is not very good, and the risk of death is so great that this method is just too risky to try. But how does it in fact line up to our new definition of success. One caveat is that I can not find a listing of the average age of the patients in TT2, so I am assuming that in this population of 668 patients that they represent a fair approximation of the average myeloma patients age. The table of deaths for the UAMS TT2 multiple myeloma protocol that is referenced here has a 12 year time-frame and is as follows:
Myeloma-related mortality - 163/668
Mortality causes unknown - 89/668
Treatment-related mortality - 51/668
Total deaths - 303/668 = 45.3%
Therefore, the death rate for TT2 for this 12 year period is 45.3% of the patients, however if you are just an average run of the mill American at age 70 (which is the average age of a myeloma patient) the death rate after 12 years is 45.0% based on these same actuarial tables. So no matter how you slice the total deaths into this or that bucket, the total number of deaths are at the definition of CURE as I defined it above. What is crazy about this is that TT3 has better results and probably shows a survival for patients greater than that for the average American.
One other interesting point is that this kind of performance is being reported in other myeloma specialists data. Dr. Berenson's, a proponent of control, is close to our definition of success, and I believe there will be many more that will show similar results in the future. I believe there is more reason for HOPE now than there ever has been.
Best Regards/Gary Petersen [email protected]
First and foremost what is the objective for each of these treatment methods? On the side of control, the objective is to be able to provide a treatment plan that provides control of the disease over time. This can be the sequential use of drugs to maintain a manageable level of the disease, with the next available treatment ready for use at relapse. It can also include up front or delayed use of autologous stem cell transplant, with many treatment options available at relapse. The preferred result is to have the patient die of something that is not myeloma related. The objective of cure is usually to provide either an allogeneic transplant or a very aggressive treatment plan that includes most available drugs plus the autologous transplant(maybe dual), consolidation, and maintenance to eliminate the disease or put it back into a MGUS stage. The preferred result is the same, which is to have the patient die of something that is not myeloma related.
There of course is the question of Quality of Life, but isn't this a question of preference. Do you want to go the control route, and have the constant fear of relapse hanging over your head, or do you want to take the up front aggressive treatment with transplant and maintenance drugs for 3 years to achieve cure.
But how can anyone determine success? What is the measure of success? How can you know if an patient has met the definition of "dying from something that is not myeloma related". If a myeloma patient dies from a heart attack, how can anyone know that the myeloma or the myeloma treatments did not have some impact in the outcome. The devils advocate could have a field day on either side of cure or control. So what would be a good surrogate for success. I believe that if a patient outlives the average American of the same age, this would be a fair measurement of success. The average American at age 70 (this is the average age of myeloma patients), will on average live an additional 16 years. This is based on the Social Security Death Rate table. If a 70 year old myeloma patient lives to age 86 then I would say he has met this definition of success. This same analysis can be accomplished for any myeloma patient no matter what the age.
A recent debate on the Forum of the Myeloma Beacon questions the high number of patients that have died from other unknown causes in the Total Therapy 2 (TT2) program which was conducted by the Arkansas UAMS program. It is surmised that because the other unknown causes of death is 29% of the total deaths, that this means that the performance of TT2 is not very good, and the risk of death is so great that this method is just too risky to try. But how does it in fact line up to our new definition of success. One caveat is that I can not find a listing of the average age of the patients in TT2, so I am assuming that in this population of 668 patients that they represent a fair approximation of the average myeloma patients age. The table of deaths for the UAMS TT2 multiple myeloma protocol that is referenced here has a 12 year time-frame and is as follows:
Myeloma-related mortality - 163/668
Mortality causes unknown - 89/668
Treatment-related mortality - 51/668
Total deaths - 303/668 = 45.3%
Therefore, the death rate for TT2 for this 12 year period is 45.3% of the patients, however if you are just an average run of the mill American at age 70 (which is the average age of a myeloma patient) the death rate after 12 years is 45.0% based on these same actuarial tables. So no matter how you slice the total deaths into this or that bucket, the total number of deaths are at the definition of CURE as I defined it above. What is crazy about this is that TT3 has better results and probably shows a survival for patients greater than that for the average American.
One other interesting point is that this kind of performance is being reported in other myeloma specialists data. Dr. Berenson's, a proponent of control, is close to our definition of success, and I believe there will be many more that will show similar results in the future. I believe there is more reason for HOPE now than there ever has been.
Best Regards/Gary Petersen [email protected]
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