We all know that there has been a lot discussion lately about early treatment of certain smoldering myeloma (SMM) patients who are at a very high risk of progressing to multiple myeloma.
I was thinking about that recently, and I got to wondering: What risk of progression justifies active treatment of a smoldering myeloma patient?
I mean, if someone has a 50 percent of progressing to symptomatic myeloma within 2 years, is that a high enough probability to justify treatment?
Or should the cutoff be 75 percent? Or 33 percent?
And is it just a single number like the probability of progressing within 2 years, or that and more, like the 2-year probability and the 5-year probability?
It seems to me that the answers to these questions are going to depend on each person's preferences for risk, which themselves may depend on things like age, general health, etc.
So, if you are smoldering, or if even if you're not, what percent probability of progressing to symptomatic myeloma within, say, two years would convince you to be actively treated, rather than doing watch and wait?
I don't have an answer to this question yet myself, but I thought I would throw it out for others to think about and share their thinking on it.
Forums
Re: What probability of progression justifies treating SMM?
Hello JimNY,
Your question is significant but it assumes that treatment for high risk SMM is standard practice and included in the guidelines published by the NCCN. Unfortunately, while research is trending in that direction, the only approved treatment for high risk SMM, to my knowledge, is clinical trials. Furthermore, all SMM clinical trials require an abnormal FLC ratio to qualify.
I have been on antibiotics 6 times in the last 11 months and I'm still considered "asymptomatic" by these guidelines, so there is still much work to do!
Best
J
Your question is significant but it assumes that treatment for high risk SMM is standard practice and included in the guidelines published by the NCCN. Unfortunately, while research is trending in that direction, the only approved treatment for high risk SMM, to my knowledge, is clinical trials. Furthermore, all SMM clinical trials require an abnormal FLC ratio to qualify.
I have been on antibiotics 6 times in the last 11 months and I'm still considered "asymptomatic" by these guidelines, so there is still much work to do!
Best
J
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jhorner - Name: Magpie
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: 2013
- Age at diagnosis: 49
Re: What probability of progression justifies treating SMM?
Jhorner,
While I used to think that one could only get covered by insurance for treatment if one was truly symtomatic by the NCCN guidelines, I no longer believe that to be true. It is now my understanding that doctors can recommend treatment based on a very high plasma cell percentage, etc. However, I imagine that there is always the risk that a given insurance carrier may still deny that coverage based on their own policy bulletins and the NCCN guidelines ... but that denial is not a given.
Now, having said that, there is the issue of doing what's best for the overall medical and multiple myeloma community. To that end, doing early treatment under the umbrella of a clinical trial is the "right" thing to do ... otherwise, information that may be valuable to researchers and ultimately other smoldering patients is lost.
But I also totally get that participating in a trial simply may not be an option for many given the geographical restrictions of where trials are conducted. Put another way, unless I had access to a trial within a 100-150 miles of me, and I needed to go in every week or two for treatment, I would simply opt for treatment outside of the trial ... if the same drugs were available to me outside of the trial setting.
While I used to think that one could only get covered by insurance for treatment if one was truly symtomatic by the NCCN guidelines, I no longer believe that to be true. It is now my understanding that doctors can recommend treatment based on a very high plasma cell percentage, etc. However, I imagine that there is always the risk that a given insurance carrier may still deny that coverage based on their own policy bulletins and the NCCN guidelines ... but that denial is not a given.
Now, having said that, there is the issue of doing what's best for the overall medical and multiple myeloma community. To that end, doing early treatment under the umbrella of a clinical trial is the "right" thing to do ... otherwise, information that may be valuable to researchers and ultimately other smoldering patients is lost.
But I also totally get that participating in a trial simply may not be an option for many given the geographical restrictions of where trials are conducted. Put another way, unless I had access to a trial within a 100-150 miles of me, and I needed to go in every week or two for treatment, I would simply opt for treatment outside of the trial ... if the same drugs were available to me outside of the trial setting.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: What probability of progression justifies treating SMM?
Thanks for the replies, jhorner and Multibilly.
I should have made it clear that my question is a hypothetical one. I know that active treatment of smoldering myeloma is currently not recommended outside of a clinical trial, regardless of a patient's risk of progression.
I also know, however, that there are discussions going on among myeloma experts about the possibility of changing this recommendation. This comes up regularly here in the forum and in Beacon articles, where people have talked about the possibility of an "ultra high risk" smoldering myeloma category being discussed in general and with them in particular. My interpretation has been that treatment eventually may be recommended for these patients if a commonly accepted definition of the category is agreed to.
That's what got me thinking: What risk of progression should be a justification for treatment? The experts will make their own call on that question, but what do people with smoldering myeloma and multiple myeloma think should be the right cutoff to justify treatment?
I hope this clarifies the question a bit.
I should have made it clear that my question is a hypothetical one. I know that active treatment of smoldering myeloma is currently not recommended outside of a clinical trial, regardless of a patient's risk of progression.
I also know, however, that there are discussions going on among myeloma experts about the possibility of changing this recommendation. This comes up regularly here in the forum and in Beacon articles, where people have talked about the possibility of an "ultra high risk" smoldering myeloma category being discussed in general and with them in particular. My interpretation has been that treatment eventually may be recommended for these patients if a commonly accepted definition of the category is agreed to.
That's what got me thinking: What risk of progression should be a justification for treatment? The experts will make their own call on that question, but what do people with smoldering myeloma and multiple myeloma think should be the right cutoff to justify treatment?
I hope this clarifies the question a bit.
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JimNY
Re: What probability of progression justifies treating SMM?
For me, this is really hard to answer. If I had some very high risk markers, I would personally be talking to at least two top multiple myeloma specialists and I would then weigh their inputs and make a decision. So, in this case, I wouldn't base my personal choice on percentages, standing recommendations from bodies such as the NCCN or IMWG, or clinical trial stats, but rather on professional opinions of the specialists I know and have come to trust.
One of my top specialists also believes that I would likely be restricting my choices down the road if I "start the chemo clock" too early. In the back of my mind, I'm also interested in delaying treatment as long as possible, in the hopes that I will have access to better drug protocols down the road (and the results from more clinical trials to help guide me).
One of my top specialists also believes that I would likely be restricting my choices down the road if I "start the chemo clock" too early. In the back of my mind, I'm also interested in delaying treatment as long as possible, in the hopes that I will have access to better drug protocols down the road (and the results from more clinical trials to help guide me).
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: What probability of progression justifies treating SMM?
Thanks for your thoughts, Multibilly.
What you wrote highlights an assumption in my original question which is unproven. To simplify things, I assumed that someone with SMM who has a 100 percent chance of progressing to multiple myeloma in 2 years would be better off being treated now than later.
That may not be the case. It may actually be better to wait until the disease progresses to the symptomatic stage, or just before it, to start treating it.
If that's a serious possibility, however, then why is there such a focus on dividing smoldering myeloma patients more accurately into different risk categories? I know a lot of that discussion has to do with just pulling together all the research being done on the subject to make the agreed-upon assessment of risk better.
It also seems to me, though, that an underlying assumption in a lot of the work is that, once we identify the "really high risk" patients, those will be the ones it makes sense to treat early. You can see this reflected in this article from the Beacon,
"Researchers Propose “Blueprint” For Pursuing A Multiple Myeloma Cure," The Myeloma Beacon, June 28, 2013
which basically argues that a key step to curing myeloma is figuring out which people who have smoldering myeloma, or MGUS, really have the version of the disease that is going to become symptomatic, and then treating those people.
Maybe I'm misinterpreting the argument in the article, but I think that's what it is, and I think similar thinking is the basis for trying to figure out which smoldering patients are at a very high risk of progressing to symptomatic disease.
What you wrote highlights an assumption in my original question which is unproven. To simplify things, I assumed that someone with SMM who has a 100 percent chance of progressing to multiple myeloma in 2 years would be better off being treated now than later.
That may not be the case. It may actually be better to wait until the disease progresses to the symptomatic stage, or just before it, to start treating it.
If that's a serious possibility, however, then why is there such a focus on dividing smoldering myeloma patients more accurately into different risk categories? I know a lot of that discussion has to do with just pulling together all the research being done on the subject to make the agreed-upon assessment of risk better.
It also seems to me, though, that an underlying assumption in a lot of the work is that, once we identify the "really high risk" patients, those will be the ones it makes sense to treat early. You can see this reflected in this article from the Beacon,
"Researchers Propose “Blueprint” For Pursuing A Multiple Myeloma Cure," The Myeloma Beacon, June 28, 2013
which basically argues that a key step to curing myeloma is figuring out which people who have smoldering myeloma, or MGUS, really have the version of the disease that is going to become symptomatic, and then treating those people.
Maybe I'm misinterpreting the argument in the article, but I think that's what it is, and I think similar thinking is the basis for trying to figure out which smoldering patients are at a very high risk of progressing to symptomatic disease.
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JimNY
Re: What probability of progression justifies treating SMM?
Appreciate you bringing up this issue.
In addition to considerations about who is probably going to evolve soon, starting the chemo clock too early, and waiting for better treatment options, I also grapple with quality of life vs potential drug side effects, and whether there is preventable silent organ damage.
It seems to be a gamble either way. Is it foolish hope that the best compromise is to monitor very closely and to treat as soon as there is a negative trend?
In addition to considerations about who is probably going to evolve soon, starting the chemo clock too early, and waiting for better treatment options, I also grapple with quality of life vs potential drug side effects, and whether there is preventable silent organ damage.
It seems to be a gamble either way. Is it foolish hope that the best compromise is to monitor very closely and to treat as soon as there is a negative trend?
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Blee - Name: Blee
- Who do you know with myeloma?: me
- When were you/they diagnosed?: Oct 2013
- Age at diagnosis: 58
Re: What probability of progression justifies treating SMM?
Hi Blee,
You bring up a good point about quality of life. I would think that is something that affects the probability cutoff people have in their mind when deciding: Should I treat the disease early, or should I wait and see if I really progress.
The upside of early treatment is the possibility of longer overall survival ... potentially a lot longer overall survival.
The downside is the possibility that you may be treating a version of the disease that will never progress to being symptomatic, despite the possibility that it may, or that you may be treating disease that will become symptomatic, but doing so will end up having no impact on how long you live.
Plus, as you said, there are also the downsides of the short-term and potential long-term side effects of treatment, and the financial cost.
I guess the reason I asked this question is that myeloma experts seem to be debating what probability of progression may justify early treatment, but what about the PATIENT perspective?
What probability is enough for most PATIENTS to say: Yeah, that's a high enough probability for me. I think I'll go for treating the disease rather than waiting to see what happens.
You bring up a good point about quality of life. I would think that is something that affects the probability cutoff people have in their mind when deciding: Should I treat the disease early, or should I wait and see if I really progress.
The upside of early treatment is the possibility of longer overall survival ... potentially a lot longer overall survival.
The downside is the possibility that you may be treating a version of the disease that will never progress to being symptomatic, despite the possibility that it may, or that you may be treating disease that will become symptomatic, but doing so will end up having no impact on how long you live.
Plus, as you said, there are also the downsides of the short-term and potential long-term side effects of treatment, and the financial cost.
I guess the reason I asked this question is that myeloma experts seem to be debating what probability of progression may justify early treatment, but what about the PATIENT perspective?
What probability is enough for most PATIENTS to say: Yeah, that's a high enough probability for me. I think I'll go for treating the disease rather than waiting to see what happens.
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JimNY
Re: What probability of progression justifies treating SMM?
Jim,
I guess something I've also learned from this site is that the process of "watching and waiting" drives some people absolutely bonkers. I don't personally fall into that camp, and I'm completely content (in fact, thankful) to be in a position to watch and wait, rather than to initiate formal treatment and take on all the attendant risks and hassles of treatment.
But, if there were an official, new threshold for when to treat "high risk" smoldering patients (i.e. x % plasma cell burden coupled with y cytogenetics, or whatever the criteria might be), and one's insurance covered treatment at this stage, I think many smoldering patients would initiate the treatment simply to end their angst between the tests for progression to symptomatic multiple myeloma.
I guess something I've also learned from this site is that the process of "watching and waiting" drives some people absolutely bonkers. I don't personally fall into that camp, and I'm completely content (in fact, thankful) to be in a position to watch and wait, rather than to initiate formal treatment and take on all the attendant risks and hassles of treatment.
But, if there were an official, new threshold for when to treat "high risk" smoldering patients (i.e. x % plasma cell burden coupled with y cytogenetics, or whatever the criteria might be), and one's insurance covered treatment at this stage, I think many smoldering patients would initiate the treatment simply to end their angst between the tests for progression to symptomatic multiple myeloma.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: What probability of progression justifies treating SMM?
This is definitely a question I (along with others) struggle with.
For me, being "ultra high risk", I was prepared to start treatment. The medications are still sitting in my pantry. I get monthly labwork, and for the past 2 months, my numbers have gone down (relatively). I know I will need to start, but quite frankly, I'm terrified.
The key for me is creatinine. As soon as it approaches 0.99, my doctor will "demand" I start. Also, I agree 100% with Blee: Is there silent organ damage that could be prevented with early treatment? Or by starting treatment early, does it start the ball rolling?
Then there's the ongoing debate as to what kind of treatment (drugs vs. stem cell transplant ... sorry ... NOT bringing THAT one up!) Different struggle!
Anyway, I don't think you can use "risk of progression" as the black and white determining factor to start treatment. Those are just statistics. My opinion is to monitor labs and look for trends (real numbers / evidence), then start treatment as soon as CRAB is imminent.
For me, being "ultra high risk", I was prepared to start treatment. The medications are still sitting in my pantry. I get monthly labwork, and for the past 2 months, my numbers have gone down (relatively). I know I will need to start, but quite frankly, I'm terrified.
The key for me is creatinine. As soon as it approaches 0.99, my doctor will "demand" I start. Also, I agree 100% with Blee: Is there silent organ damage that could be prevented with early treatment? Or by starting treatment early, does it start the ball rolling?
Then there's the ongoing debate as to what kind of treatment (drugs vs. stem cell transplant ... sorry ... NOT bringing THAT one up!) Different struggle!
Anyway, I don't think you can use "risk of progression" as the black and white determining factor to start treatment. Those are just statistics. My opinion is to monitor labs and look for trends (real numbers / evidence), then start treatment as soon as CRAB is imminent.
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gardengirl - Name: gardengirl
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Nov. 2013
- Age at diagnosis: 47
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