The well respected Mayo Clinics have produced what are clearly helpful guidelines based on their institutions experience,based on 'multiple myeloma characteristics / treatment /responses of patients'.
Quite often,clinicians may have to adjust dosages and regimes based on both the pre-existing general health status, (a patient can be in good health with no infections, but bone lesions / paraprotiens, before treatment, but their body is such that treatment puts them at high risk during treatment.
That means treatment may not be 'static, but dynamic to be tailored,for non transplant eligible patients young or old and those whose ACST fails or for whom remission is short lived. This can mean that drug combinations or dosages may be changed periodically.
If relapse comes earlier because of this does that make such patients fall into high risk, even if their initial response to treatment was very good, even if not quite a complete response? Disease staging and cytogentics, as opposed to gene enzyme profiling identifying rogue genes /products to target, do not always predict how an individual will respond.
So much is unknown and institutions come from their own positions, when although many novel myeloma drugs have been around a longer time, we are only more recently, through not exactly in comparable head to head studies gathering information to try to make sense of treatments that warrant inclusion in national guidelines. These studies do not always give detailed information about patients health history, as would case studies.
How are we as multiple myeloma patients to determine risk for ourselves beyond the current paradigm of disease staging plus iFISH cytogentics? Some people, many probably do not know their cytogenetic profile.anyway. We know some cytogenetics has poor prognosis from repeated studies. But the intermediate and standard risk seem less well agreed upon? Is this so?
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Re: MSmart guidlines-variable responses to different treatme
Hello Edna:
You raised many thoughtful and important questions that from my reading are in debate among the several leading myeloma experts in the national/international community, and you make a very good point about the Msmart Guidelines no longer really applying as written when "curveballs" creep in, and the doctors and patients have to make decisions, without in many cases any "proven" studies to inform them of the right thing to do.
The population of newly diagnosed multiple myeloma patients in the US is about 25,000 per year, but if you are talking about a subgroup of less than 10% with a relatively rare fish condition, or other condition, just on the basis of the numbers it is a challenge to collect them into a proper clinical study to get good answers.
I wanted to comment just on the issue of whether or not fast relapse is the same thing as "high risk". Fast relapse discussions in the research is very confusing. I have read that in some studies that there is better PFS of one treatment over another, but does not translate into improved OS. I take away that PFS is not most important. In other studies, I have actually read that duration of first remission is the single most important overall prognostic indicator. These two statements are to me contradictory.
There are numerous studies that look at factors that relate to expected prognosis. When its looking at cytogenetics, they call it high or low risk. There are other factors, such as bone or organ damage. If you have a lot of bone damage, its called a negative prognostic indicator. Some people can get the bone damage addressed, and they can deal with it, but overall, its a negative factor. If you are "asymptomatic" or almost, that is a positive prognostic indicator. So these factors are not exactly high/low risk as in cytogenetics, but in reality they are related and almost the same thing.
Getting back to fast relapse, I think the primary thing I have read is that usually (not always), each subsequent relapse will be of shorter duration. This is almost certainly true if you are using the same class of meds. Completely new meds in the pipeline, we all hope might improve this. If you are near asymptomatic, and had a long first remission (say 5+ years), you are in very good shape. If you relapse was faster (say 2.5 yrs), but without symptoms, at least you can treat the disease, but you might be back at it in less time than 2.5 years, not as good a situation as the first case. I have read that the "guideline" for a decent remission after ASCT is two years.
My wife had her ASCT in February. Thank God she is near asymptomatic, and feeling good.. Response is very close to CR, not quite there (we would be happier if it got there). We are researching and talking to the doctors to see what we might do to get as long a PFS as possible. There are no clear cut answers, and what is probably the "best" thing to do will have to be based on insight, hope and faith. I have read many, many studies, and the answer is not there. The best thing to do is to probably incorporate one of the "pipeline" treatments. For these treatments, the studies with PFS and OS data are several years away, but the decision will have to be made sooner that that.
Hope these thought help. Best Regards, JPC
You raised many thoughtful and important questions that from my reading are in debate among the several leading myeloma experts in the national/international community, and you make a very good point about the Msmart Guidelines no longer really applying as written when "curveballs" creep in, and the doctors and patients have to make decisions, without in many cases any "proven" studies to inform them of the right thing to do.
The population of newly diagnosed multiple myeloma patients in the US is about 25,000 per year, but if you are talking about a subgroup of less than 10% with a relatively rare fish condition, or other condition, just on the basis of the numbers it is a challenge to collect them into a proper clinical study to get good answers.
I wanted to comment just on the issue of whether or not fast relapse is the same thing as "high risk". Fast relapse discussions in the research is very confusing. I have read that in some studies that there is better PFS of one treatment over another, but does not translate into improved OS. I take away that PFS is not most important. In other studies, I have actually read that duration of first remission is the single most important overall prognostic indicator. These two statements are to me contradictory.
There are numerous studies that look at factors that relate to expected prognosis. When its looking at cytogenetics, they call it high or low risk. There are other factors, such as bone or organ damage. If you have a lot of bone damage, its called a negative prognostic indicator. Some people can get the bone damage addressed, and they can deal with it, but overall, its a negative factor. If you are "asymptomatic" or almost, that is a positive prognostic indicator. So these factors are not exactly high/low risk as in cytogenetics, but in reality they are related and almost the same thing.
Getting back to fast relapse, I think the primary thing I have read is that usually (not always), each subsequent relapse will be of shorter duration. This is almost certainly true if you are using the same class of meds. Completely new meds in the pipeline, we all hope might improve this. If you are near asymptomatic, and had a long first remission (say 5+ years), you are in very good shape. If you relapse was faster (say 2.5 yrs), but without symptoms, at least you can treat the disease, but you might be back at it in less time than 2.5 years, not as good a situation as the first case. I have read that the "guideline" for a decent remission after ASCT is two years.
My wife had her ASCT in February. Thank God she is near asymptomatic, and feeling good.. Response is very close to CR, not quite there (we would be happier if it got there). We are researching and talking to the doctors to see what we might do to get as long a PFS as possible. There are no clear cut answers, and what is probably the "best" thing to do will have to be based on insight, hope and faith. I have read many, many studies, and the answer is not there. The best thing to do is to probably incorporate one of the "pipeline" treatments. For these treatments, the studies with PFS and OS data are several years away, but the decision will have to be made sooner that that.
Hope these thought help. Best Regards, JPC
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JPC - Name: JPC
Re: MSmart guidlines-variable responses to different treatme
Hi JPC
Thanks for your response. As the population with myeloma is small subdividing people into smaller and smaller 'categories' clearly becomes statistically a non starter as you have to have a certain number to make statistical inferences. Clinical trials have rigid criteria for acceptance, save for cytogenetics / stage, and are designed to generate figures to say something about the trial results for a defined group.
The problem is as you say it is often either a guess on relapse as to what might be best treatment. Yes if you had a protesome inhibitor included for induction, you would not be given one on relapse necessarily. More difficult where you have two 'novel' drugs, immunomodulatory and proteosome inhibiting, included in the first treatment,then you have to move on to 'next generation' ones probably on second relapse. The drugs / treatments in the pipeline are a lottery to access, as access to particular trials is often country based.
The research is far from definitive and to try and put a review together, where there is internationally agreed consensus on treatment under very defined conditions of patient and protocol, is at this time impossible. So treatment on relapse is based on what national guidelines allow within their budget or individual approaches by specialists allow, the clinician cannot know if they made the right decision for the patient, nor can the patient. This is often only through hindsight reflection.
In general yes each median time to progress to relapse is generally shorter, but not necessarily on an individual basis. Aggressive relapses require aggressive treatments, usually three drug regimes which may include an alkylator. Whether PFS is better than the last period may depend on how 'aggressive' the treatment regime previously was. How aggressive a treatment is possible depends on the pre-existing health issues of the patient, where ongoing monitoring and supportive care might need to be more intensive/ well defined, to ensure treatment is at its optimal.
I was not thinking about those who had ASCT's, Although 18 months to 2 years is quoted as median there are those where this fails and yet have been on long treatment for a good many years, and are there who never had an ASCT, perhaps due to not being able to every reach low enough para protein level, who also live a good few years. It seems those most susceptible to poor decisions/ agrgessive disease progression or lack of timely diagnosis with advanced disease and susceptibility to infections will be the around 20% who die within a year of diagnosis.
I think the issue of 'risk' is multi- faceted and harder to determine than we realise, except for 17p deletions and similar negative well established high risk cytogenetics. But as you say the debates on some of the other abnormalities generates debate and research amongst the myeloma expert community.
I am pleased your wife is responding well, it seems that many people seek CR or sCR, which is hard to achieve, or takes time after a transplant. Maybe a tanden transplant, which seems to be advocated is one way. It will be interesting to see if your doctors suggest this for your wife,
Edna
Thanks for your response. As the population with myeloma is small subdividing people into smaller and smaller 'categories' clearly becomes statistically a non starter as you have to have a certain number to make statistical inferences. Clinical trials have rigid criteria for acceptance, save for cytogenetics / stage, and are designed to generate figures to say something about the trial results for a defined group.
The problem is as you say it is often either a guess on relapse as to what might be best treatment. Yes if you had a protesome inhibitor included for induction, you would not be given one on relapse necessarily. More difficult where you have two 'novel' drugs, immunomodulatory and proteosome inhibiting, included in the first treatment,then you have to move on to 'next generation' ones probably on second relapse. The drugs / treatments in the pipeline are a lottery to access, as access to particular trials is often country based.
The research is far from definitive and to try and put a review together, where there is internationally agreed consensus on treatment under very defined conditions of patient and protocol, is at this time impossible. So treatment on relapse is based on what national guidelines allow within their budget or individual approaches by specialists allow, the clinician cannot know if they made the right decision for the patient, nor can the patient. This is often only through hindsight reflection.
In general yes each median time to progress to relapse is generally shorter, but not necessarily on an individual basis. Aggressive relapses require aggressive treatments, usually three drug regimes which may include an alkylator. Whether PFS is better than the last period may depend on how 'aggressive' the treatment regime previously was. How aggressive a treatment is possible depends on the pre-existing health issues of the patient, where ongoing monitoring and supportive care might need to be more intensive/ well defined, to ensure treatment is at its optimal.
I was not thinking about those who had ASCT's, Although 18 months to 2 years is quoted as median there are those where this fails and yet have been on long treatment for a good many years, and are there who never had an ASCT, perhaps due to not being able to every reach low enough para protein level, who also live a good few years. It seems those most susceptible to poor decisions/ agrgessive disease progression or lack of timely diagnosis with advanced disease and susceptibility to infections will be the around 20% who die within a year of diagnosis.
I think the issue of 'risk' is multi- faceted and harder to determine than we realise, except for 17p deletions and similar negative well established high risk cytogenetics. But as you say the debates on some of the other abnormalities generates debate and research amongst the myeloma expert community.
I am pleased your wife is responding well, it seems that many people seek CR or sCR, which is hard to achieve, or takes time after a transplant. Maybe a tanden transplant, which seems to be advocated is one way. It will be interesting to see if your doctors suggest this for your wife,
Edna
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