I have kappa light chain multiple myeloma. My latest free light chain assay results show both kappa and lambda free light chains within normal ranges, but my kappa/lambda ratio is flagged as high.
One explanation for these findings that I've found says that
"If the kappa and lambda levels are both within the normal range, sometimes the ratio may be abnormal. In this situation, there may be a persistent low level of active myeloma with excess production of the abnormal light chains."
I am having a hard time understanding this explanation. Because it seems to me that if there is "excess production of the abnormal light chains," that would imply that one or both of the kappa or lambda free light chain levels would be abnormally high.
But that would not be the case if the levels of both types of free light chains as revealed by the assays are within the normal range. Or is there some other sense of "excess production"?
Moreover, exactly how would one determine that there is a "persistent low level of active myeloma." Are the assays not a measure of how active the myeloma is for those with light chain multiple myeloma?
Perhaps I am missing something obvious here. Can anyone explain what that might be?
Forums
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MrPotatohead - Name: MrPotatohead
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: March, 2015
- Age at diagnosis: 65
Re: Normal kappa & lambda FLC levels, but high ratio
Hello MrP,
I can understand your confusion on this issue. There was a discussion a while back started by Mrozdav that I think you may find very relevant to the questions you've raised. See what you think:
https://myelomabeacon.org/forum/low-lambda-high-kappa-lambda-ratio-iga-kappa-myeloma-t5831.html
There may be a few other discussions involving posters who have high FLC ratios that also may have some helpful information. You may want to check this list of discussions to see if any of them are are of additional help.
https://myelomabeacon.org/forum/search.php?keywords=high+ratio&terms=all&author=&sc=1&sf=titleonly&sr=topics&sk=t&sd=d&st=0&ch=300&t=0&submit=Search
I hope this helps get you pointed in the right direction. I'll check in again in the next day or two and will add more thoughts if you think that would be helpful.
Cheers!
I can understand your confusion on this issue. There was a discussion a while back started by Mrozdav that I think you may find very relevant to the questions you've raised. See what you think:
https://myelomabeacon.org/forum/low-lambda-high-kappa-lambda-ratio-iga-kappa-myeloma-t5831.html
There may be a few other discussions involving posters who have high FLC ratios that also may have some helpful information. You may want to check this list of discussions to see if any of them are are of additional help.
https://myelomabeacon.org/forum/search.php?keywords=high+ratio&terms=all&author=&sc=1&sf=titleonly&sr=topics&sk=t&sd=d&st=0&ch=300&t=0&submit=Search
I hope this helps get you pointed in the right direction. I'll check in again in the next day or two and will add more thoughts if you think that would be helpful.
Cheers!
Re: Normal kappa & lambda FLC levels, but high ratio
Good day Mr. PH: One very quick point. The induction medicines for my wife suppressed the light chains. The Kappa had come in very close to zero as a result. The K/L was very low, and out of range. So if one of the two #'s is excessively suppressed, the ratio will come up wrong. I noticed this and asked the dr. if it was the case as I described, and the dr. replied that it was correct. In any case, it does bounce around pretty significantly. Good luck
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JPC - Name: JPC
Re: Normal kappa & lambda FLC levels, but high ratio
Hello Ian
Thank you very much for referencing those posts. I need to get better at using the search function.
However, after reading them, my confusion remains. Apparently, the normal range for the kappa/lambda flc ratio is computed differently than the normal ranges for the kappa and lambda flc's. Perhaps there is a factor c such that the kappa flc number can be expressed as a product of a and c; and the lambda flc number can be expresses as a product of b and c, where both a and b represent the monoclonal flc's and c <= the normal polyclonal flc's. In that case, c would cancel with the ratio, and the result would be a better marker for just the monoclonal flc's.
I guess my question boils down to the math for getting the normal range of the ratio. It is not explained anywhere and seems to involve only a subset of possible values for kappa and lambda flc's. So how is the subset selected?
Hi JPC
So if the numerator or denominator of the ratio is very low, the result can be invalid. However, the test flagged the ratio as 'high" in my case. And while my lambda flc number is quite low, it is still about 1/3 of the way from the lowest to the highest normal range number for lambda flc's.
Thank you very much for referencing those posts. I need to get better at using the search function.
However, after reading them, my confusion remains. Apparently, the normal range for the kappa/lambda flc ratio is computed differently than the normal ranges for the kappa and lambda flc's. Perhaps there is a factor c such that the kappa flc number can be expressed as a product of a and c; and the lambda flc number can be expresses as a product of b and c, where both a and b represent the monoclonal flc's and c <= the normal polyclonal flc's. In that case, c would cancel with the ratio, and the result would be a better marker for just the monoclonal flc's.
I guess my question boils down to the math for getting the normal range of the ratio. It is not explained anywhere and seems to involve only a subset of possible values for kappa and lambda flc's. So how is the subset selected?
Hi JPC
So if the numerator or denominator of the ratio is very low, the result can be invalid. However, the test flagged the ratio as 'high" in my case. And while my lambda flc number is quite low, it is still about 1/3 of the way from the lowest to the highest normal range number for lambda flc's.
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MrPotatohead - Name: MrPotatohead
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: March, 2015
- Age at diagnosis: 65
Re: Normal kappa & lambda FLC levels, but high ratio
Hello Mr. PH.
You asked:
Yes, that is what I was trying to say.
I agree with you that the issue of the kappa, the lambda, and the ratio are confusing. They certainly are not exactly defined as to if there is a problem. I think some doctors have reported that the ratio in theory for a healthy person, is supposed to be more stable than the absolute values, because the natural fluctuation of the light chains are supposed to move in tandem. Accordingly, I understand that the ratio, is a little bit better of an early warning (canary) of a relapse by looking at the value of the ratio.
If both light chains are normal, but the ratio is off, I am thinking it is not necessarily a catastrophe, but it's the trend that's the issue, not either of the light chains. If there are fluctuations, up and down, in the ratio, then I think that's OK. If it's trending over time, up or down consistently, that is an early warning that one of the light chains are moving in the wrong direction.
Hope this helps.
You asked:
So if the numerator or denominator of the ratio is very low, the result can be invalid?
Yes, that is what I was trying to say.
I agree with you that the issue of the kappa, the lambda, and the ratio are confusing. They certainly are not exactly defined as to if there is a problem. I think some doctors have reported that the ratio in theory for a healthy person, is supposed to be more stable than the absolute values, because the natural fluctuation of the light chains are supposed to move in tandem. Accordingly, I understand that the ratio, is a little bit better of an early warning (canary) of a relapse by looking at the value of the ratio.
If both light chains are normal, but the ratio is off, I am thinking it is not necessarily a catastrophe, but it's the trend that's the issue, not either of the light chains. If there are fluctuations, up and down, in the ratio, then I think that's OK. If it's trending over time, up or down consistently, that is an early warning that one of the light chains are moving in the wrong direction.
Hope this helps.
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JPC - Name: JPC
Re: Normal kappa & lambda FLC levels, but high ratio
Mr PH,
Without getting into nits of which sub-ranges of "normal" kappa and lambda numbers can produce a high FLC ratio, a standard explanation of a normal lambda & kappa with a high FLC ratio from the folks that developed the serum FLC assay test and its accompanying ranges is that this can represent the presence of a monoclonal gammopathy with bone marrow suppression (aka myelosuppression). Myelosuppression is a well-known, potential side effect of various multiple myeloma drugs including the IMiDs, PIs, etc. Multiple myeloma patients are usually more familiar with the impact of myelosupression through their CBC test results with the monitoring for lowered platelet, neutrophil and/or hemoglobin levels (thrombocytopenia, neutropenia and anemia, respectively).
Having said that, I agree with Ian that this is not a catastrophe and the trend is what matters. However, you may want to look into what your CBC numbers have done over time as I believe you are still undergoing treatment, right?
Without getting into nits of which sub-ranges of "normal" kappa and lambda numbers can produce a high FLC ratio, a standard explanation of a normal lambda & kappa with a high FLC ratio from the folks that developed the serum FLC assay test and its accompanying ranges is that this can represent the presence of a monoclonal gammopathy with bone marrow suppression (aka myelosuppression). Myelosuppression is a well-known, potential side effect of various multiple myeloma drugs including the IMiDs, PIs, etc. Multiple myeloma patients are usually more familiar with the impact of myelosupression through their CBC test results with the monitoring for lowered platelet, neutrophil and/or hemoglobin levels (thrombocytopenia, neutropenia and anemia, respectively).
Having said that, I agree with Ian that this is not a catastrophe and the trend is what matters. However, you may want to look into what your CBC numbers have done over time as I believe you are still undergoing treatment, right?
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Normal kappa & lambda FLC levels, but high ratio
JPC, Multibilly
First of all, thanks for your many valuable responses clarifying issues raised in my posts and in those of many others. You are very well-informed and your knowledge sharing is invaluable.
I would not be surprised about having mylesuppression from treatment, as my current regimen consists of carfilzomib (Kyprolis), and cyclophosphamide (Cytoxan), as well as dexamethazone. I am on my fifth cycle.
And it is working. My kappa flc's, as measured by the serum assay, has steadily come down and is now within the normal range. Lambda has always been there.
And the kappa/lambda ratio is also improving: Last cycle, it was just over 4 and now, it's at about 2.5.
Some of my CBC numbers are suppressed - eg, hemoglobin at 10.8, lymphocytes at 0.9. But white blood cells are normal, as are platelets. Even for, eg., hemoglobin, it is not "crashing" as it used to, requiring procrit or transfusions.
What motivated my original post was puzzlement at how the ratio could be too high while the constituents of the ratio were both within normal ranges. I guess I am curious about the "nits" of the ratio computation, as Multibilly put it, but everything I have seen so far skirts that.
But my numbers are moving in the right direction, irrespective of that, with both the Kappa flc's and the flc ratio coming down with each cycle.
Thanks for your help.
First of all, thanks for your many valuable responses clarifying issues raised in my posts and in those of many others. You are very well-informed and your knowledge sharing is invaluable.
I would not be surprised about having mylesuppression from treatment, as my current regimen consists of carfilzomib (Kyprolis), and cyclophosphamide (Cytoxan), as well as dexamethazone. I am on my fifth cycle.
And it is working. My kappa flc's, as measured by the serum assay, has steadily come down and is now within the normal range. Lambda has always been there.
And the kappa/lambda ratio is also improving: Last cycle, it was just over 4 and now, it's at about 2.5.
Some of my CBC numbers are suppressed - eg, hemoglobin at 10.8, lymphocytes at 0.9. But white blood cells are normal, as are platelets. Even for, eg., hemoglobin, it is not "crashing" as it used to, requiring procrit or transfusions.
What motivated my original post was puzzlement at how the ratio could be too high while the constituents of the ratio were both within normal ranges. I guess I am curious about the "nits" of the ratio computation, as Multibilly put it, but everything I have seen so far skirts that.
But my numbers are moving in the right direction, irrespective of that, with both the Kappa flc's and the flc ratio coming down with each cycle.
Thanks for your help.
Last edited by MrPotatohead on Thu Jan 21, 2016 11:45 pm, edited 2 times in total.
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MrPotatohead - Name: MrPotatohead
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: March, 2015
- Age at diagnosis: 65
Re: Normal kappa & lambda FLC levels, but high ratio
Hi MrPotatohead,
I've been following this discussion, and I just noticed your statement saying
"I guess I am curious about the "nits" of the ratio computation".
You probably realize this, but it might be worth repeating for others that the free light chain ratio, or kappa/lambda ratio, is literally just the kappa free light chain level divided by the lambda free light chain level.
That is, the ratio is calculated using this simple formula:
kappa / lambda FLC ratio = (kappa FLC level) / (lambda FLC level)
As I said, you probably know this, but it might be worth making clear for others reading the thread.
I've been following this discussion, and I just noticed your statement saying
"I guess I am curious about the "nits" of the ratio computation".
You probably realize this, but it might be worth repeating for others that the free light chain ratio, or kappa/lambda ratio, is literally just the kappa free light chain level divided by the lambda free light chain level.
That is, the ratio is calculated using this simple formula:
kappa / lambda FLC ratio = (kappa FLC level) / (lambda FLC level)
As I said, you probably know this, but it might be worth making clear for others reading the thread.
Re: Normal kappa & lambda FLC levels, but high ratio
Hi Mr. PH, As another comment here, my doctor has told me that he would not change a course of treatment based solely on a change in the SFLC (serum free light chain, a.k.a. kappa and lambda results, plus ratio), but would also check on the SPEP results, for the monoclonal results. Also, the other blood tests are important to check on. (This wouldn't work for 'non-secretory patients' I think though). The K/L ratio can change a bit from one month to the next, but it is a concern if it starts to change out of normal ranges, though, from what I understand.
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
Re: Normal kappa & lambda FLC levels, but high ratio
Mr. PotatoHead: I am not sure that I will be adding anything new for you or any other reader here, but here goes. As I understand it, the kappa/ lambda ratio is an indicator of "balanced" production of free light chains (which is the goal). As in both of our cases, the kappa and lambda light chains fall within normal ranges, but that does not mean that they are in balance and that is why our ratios are a little high.
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