For hypothetical patient A, serologic relapse will occur on the third month after consecutive 15 mg/dl increases per month. At that point, the patient will be more than 20 mg/dl (200 mg/l) above what I assume was their lowest lambda free light chain level, and the increase of more than 20 mg/dl above the minimum will be confirmed by two consecutive readings a month apart.
The same reasoning would apply to hypothetical patient B. If the lambda free light chain level associated with serologic relapse was such that it could cause kidney damage, the doctor of course has the option of initiating treatment before that point. Of course, creatinine levels can be monitored more closely in the case of patients whose kidneys have been damaged.
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Re: Relapse and free light chain levels
Hello TerryH,
And thank you for your reply. I think the difficulty I found in interpreting Dr Libby's source concerned "what the baseline level, that increases in FLC levels are related to?" Reading the text, it appeared that any increase of 20 mg/dL in free light chain levels, between two tests, separated by two months would define a relapse. So, if on 1st January an absolute free light chain level of X mg/dL existed, and on 1st March this level was measured as X+20 mg/dL, then a relapse would be established.
In your post you say that actually the baseline figure is the lowest free light chain level measured, and any increases of 20 mg/dL above this minimum figure warrants a relapse. So I assume that if after a number of cycles of treatment – fluctuating FLC levels result – then your baseline figure is the lowest value in this sequence, and not necessarily the exit value of the free light chain level at the end of the first session of treatments, unless of course this exit value happened to be the lowest figure.
In terms of hypothetical patient B, your argument above make the diagnosis of relapse much easier than trying to lock together a relapse formula for free light chain levels / creatinine / eGFR. And obviously, as you say, concerns about vital organs like kidneys, could easily override the niceties of the 20 mg/dL step in free light chain levels. I suppose it was too ambitious of me to try and link renal impairment with free light chain levels, since unfortunately for Patient B, other renal effects, like hypertension and diabetes clouds the issue, when trying to determine what the sole contribution that free light chain levels makes to worsening kidney function.
Thanks again for your post.
Peter
And thank you for your reply. I think the difficulty I found in interpreting Dr Libby's source concerned "what the baseline level, that increases in FLC levels are related to?" Reading the text, it appeared that any increase of 20 mg/dL in free light chain levels, between two tests, separated by two months would define a relapse. So, if on 1st January an absolute free light chain level of X mg/dL existed, and on 1st March this level was measured as X+20 mg/dL, then a relapse would be established.
In your post you say that actually the baseline figure is the lowest free light chain level measured, and any increases of 20 mg/dL above this minimum figure warrants a relapse. So I assume that if after a number of cycles of treatment – fluctuating FLC levels result – then your baseline figure is the lowest value in this sequence, and not necessarily the exit value of the free light chain level at the end of the first session of treatments, unless of course this exit value happened to be the lowest figure.
In terms of hypothetical patient B, your argument above make the diagnosis of relapse much easier than trying to lock together a relapse formula for free light chain levels / creatinine / eGFR. And obviously, as you say, concerns about vital organs like kidneys, could easily override the niceties of the 20 mg/dL step in free light chain levels. I suppose it was too ambitious of me to try and link renal impairment with free light chain levels, since unfortunately for Patient B, other renal effects, like hypertension and diabetes clouds the issue, when trying to determine what the sole contribution that free light chain levels makes to worsening kidney function.
Thanks again for your post.
Peter
Re: Relapse and free light chain levels
Hello EP,
I think the wording of what constitutes a serological, or "biochemical", relapse in the case of free light chain myeloma is vague when it comes to a case like your patient A, where the patient's free light chain level is climbing consistently but not rapidly.
Precisely of the possibility of such a case, I would say that the definition has to involve a sustained absolute increase of at least 20 mg/dL versus the lowest FLC level the patient reached. A definition of serological relapse that hinges solely on the magnitude of the month-to-month change does not work for a case like your patient A.
But the wording is not 100 percent clear on the issue, even when you consult the fine print.
Note that this issue came up in a very similar thread last year, and JimNY also noted it was difficult to interpret the IMWG criteria with certainty:
"Free light chain criteria for relapse?" (started March 5, 2015)
Dr. Libby posted in that thread, as well. He did not address head-on the issue you bring up with your patient A. He did note, however, that he also looks at what is happening with the involved / uninvolved free light chain ratio – something we haven't really discussed.
That's a fair point, and it just goes to show that there is just as much art as there is science when it comes to this issue.
I think the wording of what constitutes a serological, or "biochemical", relapse in the case of free light chain myeloma is vague when it comes to a case like your patient A, where the patient's free light chain level is climbing consistently but not rapidly.
Precisely of the possibility of such a case, I would say that the definition has to involve a sustained absolute increase of at least 20 mg/dL versus the lowest FLC level the patient reached. A definition of serological relapse that hinges solely on the magnitude of the month-to-month change does not work for a case like your patient A.
But the wording is not 100 percent clear on the issue, even when you consult the fine print.
Note that this issue came up in a very similar thread last year, and JimNY also noted it was difficult to interpret the IMWG criteria with certainty:
"Free light chain criteria for relapse?" (started March 5, 2015)
Dr. Libby posted in that thread, as well. He did not address head-on the issue you bring up with your patient A. He did note, however, that he also looks at what is happening with the involved / uninvolved free light chain ratio – something we haven't really discussed.
That's a fair point, and it just goes to show that there is just as much art as there is science when it comes to this issue.
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