This article which I re-read the other day, and which Multibilly references in his response to an earlier forum post, raises a question in my mind.
"Different M-Spike After Stem Cell Transplantation Linked To Improved Survival (ASH 2012)", The Myeloma Beacon, January 16, 2013.
If a different m-spike after transplant is a good prognostic indicator and yet the goal is to have an m-spike of zero, then how are these seemingly competing goals reconciled?
Is a rising m-spike after transplant possibly a good sign, so long as it is a different one than the original? Is the difference revealed through immunofixation?
I hope someone can clear this up for me.
Forums
Re: Impact of different M-spike after transplant on prognosi
Hello,
These new m-spikes are usually small. These spikes are different and are not an indication for more treatment. Identification of new spikes is made through immunofixation. Most patients do not have them. The reason that "switching" improves survival is not understood, but this observation has been around for years. The abstract you quoted indicates that research in this area is continuing.
You definitely want your ORIGINAL m-spike to go to zero or as close to zero as possible with treatment or after a transplant.
Thank you for contacting us with this excellent question. I wish you the best of luck in your journey with myeloma.
These new m-spikes are usually small. These spikes are different and are not an indication for more treatment. Identification of new spikes is made through immunofixation. Most patients do not have them. The reason that "switching" improves survival is not understood, but this observation has been around for years. The abstract you quoted indicates that research in this area is continuing.
You definitely want your ORIGINAL m-spike to go to zero or as close to zero as possible with treatment or after a transplant.
Thank you for contacting us with this excellent question. I wish you the best of luck in your journey with myeloma.
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Dr. Edward Libby - Name: Edward Libby, M.D.
Beacon Medical Advisor
Re: Impact of different M-spike after transplant on prognosi
Thank you, Dr. Libby, for your reply to Andrew's question.
Andrew -- We contacted Dr. Victor Jimenez-Zepeda, the lead author of the study mentioned in your question, to see if he might be willing to respond to your question. He was kind enough to send the following reply:
Andrew -- We contacted Dr. Victor Jimenez-Zepeda, the lead author of the study mentioned in your question, to see if he might be willing to respond to your question. He was kind enough to send the following reply:
Myeloma is mainly associated with a unique monoclonal band. However, there are some cases of biclonal - and even triclonal - disease, which are quite uncommon. It has been observed that new monoclonal proteins not linked to the original one can emerge as a result of therapy (i.e., lenalidomide [Revlimid]) or even after transplant.
Our group and others have shown that, after transplant, these new monoclonal or oligoclonal bands (different from the original one) are some form of expression of immune reconstitution. These bands are not the original myeloma clones, which seem to denote some form of immune response associated to different therapies, including stem cell transplant. The Spanish group, like us, has demonstrated that these bands are associated with better clinical outcomes.
It is also interesting to note that the degree of response increases the frequency of these bands, with many cases of myeloma in complete response having a higher frequency of these oligoclonal bands.
The way these bands are assessed is by doing immunofixation, which is a test able to determine the bands emerging after different therapies, even at small amounts. In that way, patients without evidence of the original myeloma clone by flow cytometry, SPEP, UPEP and free light chain assays that exhibit these oligoclonal bands seem to have a better overall and progression free survival.
Dr. Victor Jimenez-Zepeda
Assistant Professor and Clinician Scientist
Tom Baker Cancer Centre
Calgary, Alberta
Re: Impact of different M-spike after transplant on prognosi
Thank you for both of these helpful replies. For some reason I have not had immunofixation the last two months. I will insist that the test be run next month.
One question though. Each month the test results show a single m-spike number. How can I tell if this number, which rose from 0.1 to 0.3 this past month, is the original clone or a different one or a combination of both?
One question though. Each month the test results show a single m-spike number. How can I tell if this number, which rose from 0.1 to 0.3 this past month, is the original clone or a different one or a combination of both?
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goldmine848 - Name: Andrew
- When were you/they diagnosed?: June 2013
- Age at diagnosis: 60
Re: Impact of different M-spike after transplant on prognosi
I wanted to add one more bit of information to my post above in case it matters.
At diagnosis my lambda serum free light chain level was 25.45 but after several cycles of VRD went into the normal range where it has remained.
On the other hand, at diagnosis my kappa was 0.5 and remained in the normal range. But starting about three months post-transplant the kappa went to 2.67 (outside the normal high of 1.94 and has remained in the 2.7-2.8 area.
I am interested in what this all means.
At diagnosis my lambda serum free light chain level was 25.45 but after several cycles of VRD went into the normal range where it has remained.
On the other hand, at diagnosis my kappa was 0.5 and remained in the normal range. But starting about three months post-transplant the kappa went to 2.67 (outside the normal high of 1.94 and has remained in the 2.7-2.8 area.
I am interested in what this all means.
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goldmine848 - Name: Andrew
- When were you/they diagnosed?: June 2013
- Age at diagnosis: 60
Re: Impact of different M-spike after transplant on prognosi
Hi Andrew,
You asked: "Each month the test results show a single m-spike number. How can I tell if this number, which rose from 0.1 to 0.3 this past month, is the original clone or a different one or a combination of both?"
You mentioned that you're not having immunofixation testing done on a regular basis. It's the immunofixation testing, however, that tells you the type of the M-spike you have. The electrophoresis testing, whether urine or serum, only tells you the level of the M-spike, not the type or types.
I'm not an expert by any means on these things, so I may be off with my explanation. But I think what I just said is correct.
You asked: "Each month the test results show a single m-spike number. How can I tell if this number, which rose from 0.1 to 0.3 this past month, is the original clone or a different one or a combination of both?"
You mentioned that you're not having immunofixation testing done on a regular basis. It's the immunofixation testing, however, that tells you the type of the M-spike you have. The electrophoresis testing, whether urine or serum, only tells you the level of the M-spike, not the type or types.
I'm not an expert by any means on these things, so I may be off with my explanation. But I think what I just said is correct.
Re: Impact of different M-spike after transplant on prognosi
It sounds like you have had an excellent response to therapy with normal "involved" free light chain levels as indicated by the normalization of your free lambda value.
When Dr. Jimenez-Zapeda discussed "immune reconstitution," he is referring to the fact that when myeloma is active, the abnormal clone suppresses your normal immune functions and often when patients' free lambda or kappa are high, there is depression of the "uninvolved" light chain or immunoglobulins (e.g., when IgG is high, IgA and IgM can be low).
However, after therapy, and importantly a good response to therapy, the "involved" light chain or immunoglobulin is suppressed allowing your normal immune function to return. In that setting, we often see new small M-spikes or elevations of the uninvolved light chains as the immune system in equilibrating.
To make it even more confusing, we and others have reported that after transplant, if patients are receiving lenalidomide [Revlimid] maintenance, there can be elevations of both the involved and uninvolved immunoglobulins (polyclonal gammopathy) which is associated with a favorable response. See article below.
Hope that helps!
D Zamarin et al., "Polyclonal immune activation and marrow plasmacytosis in multiple myeloma patients receiving long-term lenalidomide therapy: incidence and prognostic significance," Leukemia (23 April 2013).
When Dr. Jimenez-Zapeda discussed "immune reconstitution," he is referring to the fact that when myeloma is active, the abnormal clone suppresses your normal immune functions and often when patients' free lambda or kappa are high, there is depression of the "uninvolved" light chain or immunoglobulins (e.g., when IgG is high, IgA and IgM can be low).
However, after therapy, and importantly a good response to therapy, the "involved" light chain or immunoglobulin is suppressed allowing your normal immune function to return. In that setting, we often see new small M-spikes or elevations of the uninvolved light chains as the immune system in equilibrating.
To make it even more confusing, we and others have reported that after transplant, if patients are receiving lenalidomide [Revlimid] maintenance, there can be elevations of both the involved and uninvolved immunoglobulins (polyclonal gammopathy) which is associated with a favorable response. See article below.
Hope that helps!
D Zamarin et al., "Polyclonal immune activation and marrow plasmacytosis in multiple myeloma patients receiving long-term lenalidomide therapy: incidence and prognostic significance," Leukemia (23 April 2013).
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Dr. Heather Landau - Name: Heather Landau, M.D.
Beacon Medical Advisor
Re: Impact of different M-spike after transplant on prognosi
Thanks for the explanation Dr. Landau!
What I'm trying to get my head around is this statement:
"However, after therapy, and importantly a good response to therapy, the "involved" light chain or immunoglobulin is suppressed allowing your normal immune function to return. In that setting, we often see new small M-spikes or elevations of the uninvolved light chains as the immune system in equilibrating."
At first blush, it seems like this would be very unwelcome news. The simplistic way I'm thinking about this is: "Oh crud, now I've got new clonal lines of mutations of my other immunoglobulins in addition to the clonal lines of my original involved immunoglobulin to deal with ... I've essentially just increased the number of different variants that I now need to combat. To my thinking, it's like I've knocked down one mole in the Whac-a-Mole arcade game and two other moles pop up in its place
"
So, how does this actually end up being a good thing? Do these new clonal lines of the uninvolved immunoglobulins behave differently and just disappear on their own over time (which would be amazing and I imagine an area of research if this were the case)? Don't these new clonal lines of the uninvolved immunoglobulins also cause the same kind of damage to the body that the involved clonal lines do?
What I'm trying to get my head around is this statement:
"However, after therapy, and importantly a good response to therapy, the "involved" light chain or immunoglobulin is suppressed allowing your normal immune function to return. In that setting, we often see new small M-spikes or elevations of the uninvolved light chains as the immune system in equilibrating."
At first blush, it seems like this would be very unwelcome news. The simplistic way I'm thinking about this is: "Oh crud, now I've got new clonal lines of mutations of my other immunoglobulins in addition to the clonal lines of my original involved immunoglobulin to deal with ... I've essentially just increased the number of different variants that I now need to combat. To my thinking, it's like I've knocked down one mole in the Whac-a-Mole arcade game and two other moles pop up in its place
"So, how does this actually end up being a good thing? Do these new clonal lines of the uninvolved immunoglobulins behave differently and just disappear on their own over time (which would be amazing and I imagine an area of research if this were the case)? Don't these new clonal lines of the uninvolved immunoglobulins also cause the same kind of damage to the body that the involved clonal lines do?
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Impact of different M-spike after transplant on prognosi
From what I have read, they don't know exactly why this happens, but it does seem to be a positive prognostic indicator. Also it tends to disappear relatively quickly.
What for me was disconcerting was to see a bump up in my m-spike from 0.1 to 0.3 post-transplant. I gather that, since I did not have an immunofixation test for several months, there is no way to know whether the bump up was from the original clone or a different one.
My uninvolved immunoglobulins have not risen enough to explain the rise in m-spike so I am speculating that it might be the kappa rise that is responsible for the higher m-spike if, in fact, this a different clone.
Getting new blood work next week and I am hopeful that the doctor will grant my request to reinstate the immunofixation test.
What for me was disconcerting was to see a bump up in my m-spike from 0.1 to 0.3 post-transplant. I gather that, since I did not have an immunofixation test for several months, there is no way to know whether the bump up was from the original clone or a different one.
My uninvolved immunoglobulins have not risen enough to explain the rise in m-spike so I am speculating that it might be the kappa rise that is responsible for the higher m-spike if, in fact, this a different clone.
Getting new blood work next week and I am hopeful that the doctor will grant my request to reinstate the immunofixation test.
-
goldmine848 - Name: Andrew
- When were you/they diagnosed?: June 2013
- Age at diagnosis: 60
Re: Impact of different M-spike after transplant on prognosi
Andrew,
You are talking about your serum M-Spike that went from 0.1 to 0.3 post-transplant, right?
I always thought that the serum M-Spike only measures the monoclonal heavy chains and does not measure the free light chain content in one's serum. And the free light chain test only measures the "free" (unbound) light chains.
So, I don't think that a rise in Kappa would necessarily translate to a rise in the serum M-Spike ... although I could be wrong about all this???
I know there is now a new test on the market called HevyLite, which actually does look at the amounts of bound heavy and light chain combinations in one's serum.
Again, maybe I've go this all wrong?
You are talking about your serum M-Spike that went from 0.1 to 0.3 post-transplant, right?
I always thought that the serum M-Spike only measures the monoclonal heavy chains and does not measure the free light chain content in one's serum. And the free light chain test only measures the "free" (unbound) light chains.
So, I don't think that a rise in Kappa would necessarily translate to a rise in the serum M-Spike ... although I could be wrong about all this???
I know there is now a new test on the market called HevyLite, which actually does look at the amounts of bound heavy and light chain combinations in one's serum.
Again, maybe I've go this all wrong?
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
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