Hello everyone,
I reside in the U.K and was was referred to The Beacon by a fellow multiple myeloma sufferer who lives in Holland.
I was diagnosed with lambda light chain myeloma exactly a year ago. I entered hospital due to a nasty bout of food poisoning from eating fish (which turned out to be the culprit!). Whilst in hospital, I was diagnosed with multiple myeloma – absolutely crazy, since apart from the obvious poisoning symptoms, I felt fine. A light chain blood test revealed my lambda light chains were above 11,000, and my kidney GFR efficiency had dropped from a previously healthy >90% to around 15%. But thank goodness, after treatment cycles of Velcade, dex and thalidomide, the kidney function has recovered to about 50%.
My last cycle of treatment was in February 2016, and on exit my lambda light chain level was in the single figures (max euro ref level of 26) with the accompanying improvement in kidney function.
A month or so ago (July 2016), a new light chain test showed the lambda light chain level on the increase again – up to just over 100. All other biomarkers were okay and creatinine computed kidney GFR (or efficiency) was >50%. And no further immediate treatment was prescribed, which suits me fine, since it extends my drug free holiday and increases the time to 'a first relapse'. However; bearing in mind the context of this article,
"Myeloma Morning: Early Relapse And Survival, And Ninlaro & Kyprolis In Europe," The Myeloma Beacon, May 27, 2016
I guess it all depends on what the definition of a first relapse actually is?
Is anyone in a similar position please? Does anyone know, or can comment on, the U.S. interpretation of a first relapse, based on increases, or absolute numbers, of the light chain level?
In other words: Is it a trend issue related to light chain increases, or once the light chain level reaches a ceiling figure? Any help, advice, or comment would be much appreciated.
Very best wishes to all,
Peter
Forums
Re: Relapse and free light chain levels
Hello Peter,
Welcome to the forum. Sorry you have to be here, but you've found a very knowledgeable, supportive, and international community.
There are actually rather standardized criteria for the definition of relapse in multiple myeloma patients. They were recently refined a bit, but the ones that have been used in most countries over the past 5 to 10 years have been those from the International Myeloma Working Group. There is a summary of those criteria in this post here in the forum from the myeloma specialist Dr. Edward Libby.
Doctors sometimes classify relapses into "clinical" ("symptomatic") relapses and "serologic" relapses. You're wondering primarily about "serologic" relapses, or those where the relapse is based on the level of a patient's M-spike (monoclonal protein) or involved free light chain level (in your case, lambda is your "involved" free light chain). There is a paper from Dr. S Vincent Rajkumar, which Dr. Libby cites, and which addresses that issue. Leaving out what it says about M-spikes, here is what it writes about free light chain levels:
"a significant paraprotein relapse is defined as ... an increase in the absolute levels of ... involved FLC level by more than or equal to 20 mg/dL (plus an abnormal FLC ratio) in 2 consecutive measurements separated by less than or equal to 2 months."
Note that 20 mg/dL is 200 mg/l, and you seem to be using the mg/l scale.
Reference:
Rajkumar, SV, et al., "Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1," Blood, 2011 (full text of article)
So, for a serologic relapse to take place, you would have to have an increase in your lambda free light chain level of 200 mg/l from its minimum, confirmed by two consecutive tests, and in the presence of an abnormal kappa-lambda ratio.
I hope this clarifies things a bit. Good luck!
Welcome to the forum. Sorry you have to be here, but you've found a very knowledgeable, supportive, and international community.
There are actually rather standardized criteria for the definition of relapse in multiple myeloma patients. They were recently refined a bit, but the ones that have been used in most countries over the past 5 to 10 years have been those from the International Myeloma Working Group. There is a summary of those criteria in this post here in the forum from the myeloma specialist Dr. Edward Libby.
Doctors sometimes classify relapses into "clinical" ("symptomatic") relapses and "serologic" relapses. You're wondering primarily about "serologic" relapses, or those where the relapse is based on the level of a patient's M-spike (monoclonal protein) or involved free light chain level (in your case, lambda is your "involved" free light chain). There is a paper from Dr. S Vincent Rajkumar, which Dr. Libby cites, and which addresses that issue. Leaving out what it says about M-spikes, here is what it writes about free light chain levels:
"a significant paraprotein relapse is defined as ... an increase in the absolute levels of ... involved FLC level by more than or equal to 20 mg/dL (plus an abnormal FLC ratio) in 2 consecutive measurements separated by less than or equal to 2 months."
Note that 20 mg/dL is 200 mg/l, and you seem to be using the mg/l scale.
Reference:
Rajkumar, SV, et al., "Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1," Blood, 2011 (full text of article)
So, for a serologic relapse to take place, you would have to have an increase in your lambda free light chain level of 200 mg/l from its minimum, confirmed by two consecutive tests, and in the presence of an abnormal kappa-lambda ratio.
I hope this clarifies things a bit. Good luck!
Re: Relapse and free light chain levels
Dear TerryH,
I read with interest your response to Peter's post about the criteria for relapse, and wondered if I might ask a follow up question.
In my case, I do not show any of the clinical signs for relapse mentioned in Dr. Libby's post. I have kappa light chain multiple myeloma and, in my case, my free light chain tests, done every 1-2 months, have shown small increases in my kappa free light chains for the past few months. Here they are:
June, 2016 - 0.7820 mg/dL
July, 2016 - 0.8610 mg/dL, increase of 0.079 mg/dL
Sept, 2016 - 2.08 mg/dL, increase of 1.219 mg/dL
These are much smaller increases than what Dr. Libby mentions, and yet, with my last free light chain test result, my kappa number is no longer within the reference range, and so it appears to me that I am no longer in remission. So is this not evidence of relapse?
Thanks.
I read with interest your response to Peter's post about the criteria for relapse, and wondered if I might ask a follow up question.
In my case, I do not show any of the clinical signs for relapse mentioned in Dr. Libby's post. I have kappa light chain multiple myeloma and, in my case, my free light chain tests, done every 1-2 months, have shown small increases in my kappa free light chains for the past few months. Here they are:
June, 2016 - 0.7820 mg/dL
July, 2016 - 0.8610 mg/dL, increase of 0.079 mg/dL
Sept, 2016 - 2.08 mg/dL, increase of 1.219 mg/dL
These are much smaller increases than what Dr. Libby mentions, and yet, with my last free light chain test result, my kappa number is no longer within the reference range, and so it appears to me that I am no longer in remission. So is this not evidence of relapse?
Thanks.
-
MrPotatohead - Name: MrPotatohead
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: March, 2015
- Age at diagnosis: 65
Re: Relapse and free light chain levels
Good Morning MrPotatoehead (and Terry),
Firstly, I should say that in Europe, the serum free light chain assay units are mg/L, so I'm sorry if I left this out in my first post, and hope no confusion arose. I'm using the U.S. standard in what follows.
With increases in kappa free light chain levels of the order of 0.079 mg/dL, I would disregard this in the sense that it's probably much less than the measurement error of the test method (or the plus/minus error attached to the nominal value actually measured). At a +/- 20% error (of a nominal 0.86 mg/dL) the error alone would be plus or minus 0.172 mg/dL. So, the real range of the true measurement 0.86 + 0.172 mg/dL to 0.86 - 0.172 mg/dL. So in this sense, one has to be careful if you're dealing with very small differences in two consecutive assays. Since they're probably of little diagnostic value.
Also, the mere fact that the assay process contains equipment that can read many places of mg/dL after the decimal point - makes very little contribution to the overall accuracy of the measured answer IF the actual process (systematic / human / environmental ...) produces errors which are much greater than the number of decimal placed seen on the kit's read-out.
Assuming the kappa reference levels are 0.33 to 1.94 mg/dL, then your Sep 2016 reading of 2.08 mg/dL is outside this range. And you quote the difference as 1.219 mg/dL. However, in the paper that Terry quoted (Dr Libby), the time to next treatment (TNT), as a predictor for relapse, requires an increase in the involved free light chain of more than, or equal to, 20 mg/dL over two consecutive measurements. So it would appear that since your increase in almost one twentieth of the permitted value, then you're not in a relapse situation. It says you would also need to have an abnormal free light chain ratio.
If you look at the amended table in the paper, under the 'progressive disease' column. I found this a little ambiguous, since it appears to require an increase in 25% of some of the disease markers. In the notes at the foot of the table, it says that a 25% increase (assumed from the lowest response value) in free light chain levels would mean that the disease is in progression. The confusion arises because it also quotes a requirement for the difference between involved and uninvolved free light chain levels to be > 10 mg/dL?
So, although, you seem to meet the 25% criteria for progressive disease, I'm assuming you don't meet the 10 mg/dL figure? And it's not clear to me if both conditions need to be met, or one takes precedence over the other, for you to be declared in PD?
Best regards in your reading and research,
Peter (The English Guy)
Firstly, I should say that in Europe, the serum free light chain assay units are mg/L, so I'm sorry if I left this out in my first post, and hope no confusion arose. I'm using the U.S. standard in what follows.
With increases in kappa free light chain levels of the order of 0.079 mg/dL, I would disregard this in the sense that it's probably much less than the measurement error of the test method (or the plus/minus error attached to the nominal value actually measured). At a +/- 20% error (of a nominal 0.86 mg/dL) the error alone would be plus or minus 0.172 mg/dL. So, the real range of the true measurement 0.86 + 0.172 mg/dL to 0.86 - 0.172 mg/dL. So in this sense, one has to be careful if you're dealing with very small differences in two consecutive assays. Since they're probably of little diagnostic value.
Also, the mere fact that the assay process contains equipment that can read many places of mg/dL after the decimal point - makes very little contribution to the overall accuracy of the measured answer IF the actual process (systematic / human / environmental ...) produces errors which are much greater than the number of decimal placed seen on the kit's read-out.
Assuming the kappa reference levels are 0.33 to 1.94 mg/dL, then your Sep 2016 reading of 2.08 mg/dL is outside this range. And you quote the difference as 1.219 mg/dL. However, in the paper that Terry quoted (Dr Libby), the time to next treatment (TNT), as a predictor for relapse, requires an increase in the involved free light chain of more than, or equal to, 20 mg/dL over two consecutive measurements. So it would appear that since your increase in almost one twentieth of the permitted value, then you're not in a relapse situation. It says you would also need to have an abnormal free light chain ratio.
If you look at the amended table in the paper, under the 'progressive disease' column. I found this a little ambiguous, since it appears to require an increase in 25% of some of the disease markers. In the notes at the foot of the table, it says that a 25% increase (assumed from the lowest response value) in free light chain levels would mean that the disease is in progression. The confusion arises because it also quotes a requirement for the difference between involved and uninvolved free light chain levels to be > 10 mg/dL?
So, although, you seem to meet the 25% criteria for progressive disease, I'm assuming you don't meet the 10 mg/dL figure? And it's not clear to me if both conditions need to be met, or one takes precedence over the other, for you to be declared in PD?
Best regards in your reading and research,
Peter (The English Guy)
Re: Relapse and free light chain levels
Dear Peter,
Let me begin by thanking you for responding to my post and the question it raises. You make some very good points.
On the possibility that these small increases are due to measirement error: I decided to go back a few more months. The increases actually began in April. So here is the full list of kappa free light chain readings, starting from when the increases began. All are in mg/dL.
April 0.6700
May 0.6880
June 0.7820
July 0.8610
Sept 2.08
So I think I led you astray by not going back far enough. Given that, I would not expect random measurement errors to consistently be on the increasing side. (Before April, the numbers showed small but steady decreases, or stayed the same from month to month).
With respect to the kappa/lambda ratio, the numbers are:
April 21.5
May 4.33
June 6.57
July 28.5
Sept 14.0
The reference range for this ratio is 0.2600-1.65, so all of these ratios are outside a "normal" reading. This has been true throughout my Kyprolis treatment regimen, and my oncologist told me that my lambda number is very low due to a side effect of my treatment, and that therefore the ratio is meaningless in my case. Note however that, unlike the kappa free light chain numbers, the ratio does go up and down.
Also, the difference between the involved (kappa) and uninvolved (lambda) free light chains in my case is less than 10 mg/dL, but is often an order of magnitude. So in the case, for example, of my April readings, my kappa number is 0.6700 mg/dL and my lambda number is 0.0312 mg/dL.
All of this leaves intact the definition of relapse in terms of much higher magnitudes of increase than I have experienced, and one can indeed say that, based on those criteria, I have not relapsed. Perhaps the right way to characterize my readings is that I have moved from a complete response to a partial response.
I wonder then if my oncologist will change my treatment once I see him next and we discuss these numbers. I will post an update once that happens.
Thank you again, Peter.
Let me begin by thanking you for responding to my post and the question it raises. You make some very good points.
On the possibility that these small increases are due to measirement error: I decided to go back a few more months. The increases actually began in April. So here is the full list of kappa free light chain readings, starting from when the increases began. All are in mg/dL.
April 0.6700
May 0.6880
June 0.7820
July 0.8610
Sept 2.08
So I think I led you astray by not going back far enough. Given that, I would not expect random measurement errors to consistently be on the increasing side. (Before April, the numbers showed small but steady decreases, or stayed the same from month to month).
With respect to the kappa/lambda ratio, the numbers are:
April 21.5
May 4.33
June 6.57
July 28.5
Sept 14.0
The reference range for this ratio is 0.2600-1.65, so all of these ratios are outside a "normal" reading. This has been true throughout my Kyprolis treatment regimen, and my oncologist told me that my lambda number is very low due to a side effect of my treatment, and that therefore the ratio is meaningless in my case. Note however that, unlike the kappa free light chain numbers, the ratio does go up and down.
Also, the difference between the involved (kappa) and uninvolved (lambda) free light chains in my case is less than 10 mg/dL, but is often an order of magnitude. So in the case, for example, of my April readings, my kappa number is 0.6700 mg/dL and my lambda number is 0.0312 mg/dL.
All of this leaves intact the definition of relapse in terms of much higher magnitudes of increase than I have experienced, and one can indeed say that, based on those criteria, I have not relapsed. Perhaps the right way to characterize my readings is that I have moved from a complete response to a partial response.
I wonder then if my oncologist will change my treatment once I see him next and we discuss these numbers. I will post an update once that happens.
Thank you again, Peter.
-
MrPotatohead - Name: MrPotatohead
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: March, 2015
- Age at diagnosis: 65
Re: Relapse and free light chain levels
Hi Mr. P and Peter,
"Relapse" and "disease progression" (or "progressive disease") are different concepts. They've been discussed and clarified a bit in the past here in the forum. See this discussion, particularly the concepts by Dr. Kaufman:
https://myelomabeacon.org/forum/definition-relapse-multiple-myeloma-t4568.html
Relapse can only be used in connection with patients who have had a response to treatment. And, of the two terms, it is the one used the most with patients who have been treated and responded to treatment.
Disease progression, on the other hand, is used primarily in connection with patients who have not responded to a treatment. It's used to mark the point in time where doctors can say "This patient not only has not responded to treatment, but their disease is clearly progressing."
You may recall from reading studies about drugs being tested in patients who have received 4, 5, or 6 previous therapies that there is always a share of patients that has "progressive disease" as the best "response". Well, the criteria for disease progression are what are used to determine that group of patients. (Other patients will be considered to have "stable disease", and others will be considered to have "responded".)
It is possible, Mr. P., that you are in the early stages of relapsing. Personally, I think it's a bit too early to say whether that is true. But there is a difference between "beginning to relapse" and actual "relapse".
As explained in the Blood article I linked to, "Relapsed myeloma is defined as previously treated myeloma that progresses and requires the initiation of salvage therapy ..." That is, the definition of relapse is intended to mark the point where a patient's disease has become active enough again that many myeloma specialists would say it is time to re-start treatment or, if the patient is currently being treated, try a new treatment regimen.
As a side note, I don't think there are "U.S." and "non-U.S." units for free light chain results. It may be the case that free light chain levels are typically quoted in mg/l outside the U.S. I can't say I've really noticed. But, as best I've been able to tell, the results in the U.S. are sometimes in mg/dl, and sometimes in mg/l. That's why, particularly with free light chain results, it really is helpful when people give either units and/or reference ranges.
Finally, you may find these threads helpful, Mr. P., to get a sense of the sort of free light chain variations that are "big" and "not big".
First, see the graphs of Multibilly's lab results, keeping in mind that Multibilly is still smoldering:
https://myelomabeacon.org/forum/fenofibrate-tricor-and-multiple-myeloma-t2690-50.html#p41916
Second, see the discussion about Christina's free light chain levels that eventually led to her being considered to have relapsed:
https://myelomabeacon.org/forum/high-kappa-light-chains-t4950.html
Hope this helps a bit. Good luck!
"Relapse" and "disease progression" (or "progressive disease") are different concepts. They've been discussed and clarified a bit in the past here in the forum. See this discussion, particularly the concepts by Dr. Kaufman:
https://myelomabeacon.org/forum/definition-relapse-multiple-myeloma-t4568.html
Relapse can only be used in connection with patients who have had a response to treatment. And, of the two terms, it is the one used the most with patients who have been treated and responded to treatment.
Disease progression, on the other hand, is used primarily in connection with patients who have not responded to a treatment. It's used to mark the point in time where doctors can say "This patient not only has not responded to treatment, but their disease is clearly progressing."
You may recall from reading studies about drugs being tested in patients who have received 4, 5, or 6 previous therapies that there is always a share of patients that has "progressive disease" as the best "response". Well, the criteria for disease progression are what are used to determine that group of patients. (Other patients will be considered to have "stable disease", and others will be considered to have "responded".)
It is possible, Mr. P., that you are in the early stages of relapsing. Personally, I think it's a bit too early to say whether that is true. But there is a difference between "beginning to relapse" and actual "relapse".
As explained in the Blood article I linked to, "Relapsed myeloma is defined as previously treated myeloma that progresses and requires the initiation of salvage therapy ..." That is, the definition of relapse is intended to mark the point where a patient's disease has become active enough again that many myeloma specialists would say it is time to re-start treatment or, if the patient is currently being treated, try a new treatment regimen.
As a side note, I don't think there are "U.S." and "non-U.S." units for free light chain results. It may be the case that free light chain levels are typically quoted in mg/l outside the U.S. I can't say I've really noticed. But, as best I've been able to tell, the results in the U.S. are sometimes in mg/dl, and sometimes in mg/l. That's why, particularly with free light chain results, it really is helpful when people give either units and/or reference ranges.
Finally, you may find these threads helpful, Mr. P., to get a sense of the sort of free light chain variations that are "big" and "not big".
First, see the graphs of Multibilly's lab results, keeping in mind that Multibilly is still smoldering:
https://myelomabeacon.org/forum/fenofibrate-tricor-and-multiple-myeloma-t2690-50.html#p41916
Second, see the discussion about Christina's free light chain levels that eventually led to her being considered to have relapsed:
https://myelomabeacon.org/forum/high-kappa-light-chains-t4950.html
Hope this helps a bit. Good luck!
Re: Relapse and free light chain levels
Hi TerryH
Your latest post helps a great deal. Thanks very much.
I don't meet either the clinical or serological criteria for relapse, but my light chains are definitely rising, albeit by small increments
I guess time will tell if this is the beginning of a relapse. I am, in any case, based on my latest kappa free light chain level, no longer in complete response. Whatever the technical definitions involved, going from a complete response to a partial response to my mind is an obvious worsening of my situation.
It will be interesting to see what my oncologist says and recommends.
Your latest post helps a great deal. Thanks very much.
I don't meet either the clinical or serological criteria for relapse, but my light chains are definitely rising, albeit by small increments
I guess time will tell if this is the beginning of a relapse. I am, in any case, based on my latest kappa free light chain level, no longer in complete response. Whatever the technical definitions involved, going from a complete response to a partial response to my mind is an obvious worsening of my situation.
It will be interesting to see what my oncologist says and recommends.
-
MrPotatohead - Name: MrPotatohead
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: March, 2015
- Age at diagnosis: 65
Re: Relapse and free light chain levels
Hi again Mr P and Terry,
Mr P: Yes, thank you for sending the full account of your kappa free light chain results. And yes, the continuing rise (albeit small) would rule out random errors related to the total measurement error, so Terry's view of a 'beginning to relapse' scenario would seem about right in the circumstances.
One of the problems of dealing with multiple myeloma is that 'to treat' or 'not to treat', for example, is obviously based (amongst other things) on the results of free light chain measurements, plus the interpretation of standardized rules concerning definitions and trigger limits. To try and clarify my perspective: the question of measurement errors and repeatably of the test (with the same operator, using the same process and assay machine) is not important and not questioned if the free light chain measurements are well below, or well above, the trigger value that would change or introduce a new treatment pathway. It's when the results are nudging up to the trigger limit, or marginally beyond it, that errors could be considered. Of course, if there's an established upward trend in results, then I think this would outweigh any niceties related to errors.
I also have a mild (hopefully) prostate problem, and for various reasons I changed clinics from the one I previously attended to the same one that treats my myeloma. I had a 'current' PSA blood test result from my previous clinic which I took to my new one. And to my surprise this result was completely rejected by my new clinic - basically because of trust in the other's assay method. So confidence by everyone in test results seems pretty essential.
I hope I didn't confuse you when I introduced the PD (progression of disease) topic related to your case, but I was trying to align your results with that in the table in the article Terry mentioned, and now you've detailed all your results, I reckon you're correct regarding the change of your response category.
Incidentally, my young multiple myeloma consultant is very particular about definitions, and when I was first diagnosed a year ago, my lambda free light chain test showed a 'whopping level' of 11,500 mg/L. Yes, eleven thousand. After the first few cycles of Velcade, thalidomide, and dexamethasone, the value drastically collapsed to single figures and within the reference levels. It stayed there until February this year, which was my last treatment cycle. Unfortunately, it's now started to creep up again (117 mg/L) and at my last consultant's meeting, she told me that my multiple myeloma was starting to progress. And this was after an excellent response over the many months and 8 cycles of treatment.
So I'm not sure how this relates to the view that progressive disease is only defined if no previous response occurred? And thanks to Terry, I've attached the note from Dr Kaufman (edited) who tries to clarify the terminology:
Dr. Jonathan Kaufman wrote on Wed Dec 17, 2014 10:07 am
So again, best wishes to all,
Peter (that English guy)
Mr P: Yes, thank you for sending the full account of your kappa free light chain results. And yes, the continuing rise (albeit small) would rule out random errors related to the total measurement error, so Terry's view of a 'beginning to relapse' scenario would seem about right in the circumstances.
One of the problems of dealing with multiple myeloma is that 'to treat' or 'not to treat', for example, is obviously based (amongst other things) on the results of free light chain measurements, plus the interpretation of standardized rules concerning definitions and trigger limits. To try and clarify my perspective: the question of measurement errors and repeatably of the test (with the same operator, using the same process and assay machine) is not important and not questioned if the free light chain measurements are well below, or well above, the trigger value that would change or introduce a new treatment pathway. It's when the results are nudging up to the trigger limit, or marginally beyond it, that errors could be considered. Of course, if there's an established upward trend in results, then I think this would outweigh any niceties related to errors.
I also have a mild (hopefully) prostate problem, and for various reasons I changed clinics from the one I previously attended to the same one that treats my myeloma. I had a 'current' PSA blood test result from my previous clinic which I took to my new one. And to my surprise this result was completely rejected by my new clinic - basically because of trust in the other's assay method. So confidence by everyone in test results seems pretty essential.
I hope I didn't confuse you when I introduced the PD (progression of disease) topic related to your case, but I was trying to align your results with that in the table in the article Terry mentioned, and now you've detailed all your results, I reckon you're correct regarding the change of your response category.
Incidentally, my young multiple myeloma consultant is very particular about definitions, and when I was first diagnosed a year ago, my lambda free light chain test showed a 'whopping level' of 11,500 mg/L. Yes, eleven thousand. After the first few cycles of Velcade, thalidomide, and dexamethasone, the value drastically collapsed to single figures and within the reference levels. It stayed there until February this year, which was my last treatment cycle. Unfortunately, it's now started to creep up again (117 mg/L) and at my last consultant's meeting, she told me that my multiple myeloma was starting to progress. And this was after an excellent response over the many months and 8 cycles of treatment.
So I'm not sure how this relates to the view that progressive disease is only defined if no previous response occurred? And thanks to Terry, I've attached the note from Dr Kaufman (edited) who tries to clarify the terminology:
Dr. Jonathan Kaufman wrote on Wed Dec 17, 2014 10:07 am
I agree that these definitions can be confusing. There are differences between progression and relapse and they are somewhat subtle.
In contrast, relapse is more narrowly defined. In order for a patient to have relapsed disease, the patient has to have an initial response and then relapse from that response.
A patient with progression of disease may have either had a prior response or not.
So again, best wishes to all,
Peter (that English guy)
Re: Relapse and free light chain levels
Just to clarify something, I did not mean to imply in my earlier posts that progressive disease -- or disease progression -- is not defined when it comes to patients who have had a response to treatment. What I wrote and want to make clear is that the concept "is used primarily in connection with patients who have not responded to a treatment."
"Progressive disease" or "disease progression" is defined for patients who have responded to treatment, It's just not used as frequently in connection with such patients. This is because, for patients who have responded to treatment, it's really relapse that is the focus, as the definition of relapse seems to play the biggest role in determining when relapsing patients are started on treatment again, or have their current therapy changed.
"Progressive disease" or "disease progression" is defined for patients who have responded to treatment, It's just not used as frequently in connection with such patients. This is because, for patients who have responded to treatment, it's really relapse that is the focus, as the definition of relapse seems to play the biggest role in determining when relapsing patients are started on treatment again, or have their current therapy changed.
Re: Relapse and free light chain levels
In an earlier post in this thread, TerryH provided some useful information regarding the formal definition of a serological free light chain myeloma relapse. Quoting below, this is what Terry said (and I understand it was taken from a source referenced by Dr Libby):
"a significant paraprotein relapse is defined as ... an increase in the absolute levels of ... involved FLC level by more than or equal to 20 mg/dL (plus an abnormal FLC ratio) in 2 consecutive measurements separated by less than or equal to 2 months."
I'm assuming this definition is
i) Generally used by practitioners, in the everyday sense and not restricted to solely clinical trial assessments, and
ii) Applies whether or not a patient has undergone an stem cell transplant.
The reference range for lambda free light chains (lFLCs) is 0.571 to 2.63 mg/dL.
So take the case of Patient A, who after diagnosis has had a successful initial treatment which has produced an exit lFLC level of 1 mg/dL. His treatment then stops and he subsequently has Freelite tests every two months, and each time an increase of around 15 mg/dL is discovered.
So after the first test, his LFLC level is outside the reference range, but less than the formal increase that denotes a relapse. At the end of the first year, and after six tests, his total LFLC level will be 154 mg/dL.
My obvious question concerns how two monthly increases are viewed in conjunction with the absolute LC resulting level, for the purposes of a serological relapse definition?
Hypothetical Patient B has exactly the same lFLC level profile as Patient A, but additionally, related renal impairment, as measured by increasing creatinine levels and reducing eGFR figures. I understand that in a healthy person, the average life-cycle of an unbound FLC is between 2 and 6 hours before it (kappa or lambda version) is metabolised by the kidneys and rendered 'harmless'. Unfortunately, in Patient B's case, the increasing numbers of lFLCs are posing a threat to his kidneys, since they appear more sensitive to increasing LC levels than other myeloma patients.
My simple question concerns the relationship between lFLC and creatinine levels. Is there a combination of values that would predict a relapse? Or are the lFLC and creatinine levels inspected separately and judgements made in this way. I'm not talking about horrendous levels of FLCs (many thousands), or creatinine levels that would warrant immediate emergency dialysis. It's the lower, but still very troublesome values that I'm interested in. If anyone has any ideas, I'd be very grateful to hear from you.
Peter
"a significant paraprotein relapse is defined as ... an increase in the absolute levels of ... involved FLC level by more than or equal to 20 mg/dL (plus an abnormal FLC ratio) in 2 consecutive measurements separated by less than or equal to 2 months."
I'm assuming this definition is
i) Generally used by practitioners, in the everyday sense and not restricted to solely clinical trial assessments, and
ii) Applies whether or not a patient has undergone an stem cell transplant.
The reference range for lambda free light chains (lFLCs) is 0.571 to 2.63 mg/dL.
So take the case of Patient A, who after diagnosis has had a successful initial treatment which has produced an exit lFLC level of 1 mg/dL. His treatment then stops and he subsequently has Freelite tests every two months, and each time an increase of around 15 mg/dL is discovered.
So after the first test, his LFLC level is outside the reference range, but less than the formal increase that denotes a relapse. At the end of the first year, and after six tests, his total LFLC level will be 154 mg/dL.
My obvious question concerns how two monthly increases are viewed in conjunction with the absolute LC resulting level, for the purposes of a serological relapse definition?
Hypothetical Patient B has exactly the same lFLC level profile as Patient A, but additionally, related renal impairment, as measured by increasing creatinine levels and reducing eGFR figures. I understand that in a healthy person, the average life-cycle of an unbound FLC is between 2 and 6 hours before it (kappa or lambda version) is metabolised by the kidneys and rendered 'harmless'. Unfortunately, in Patient B's case, the increasing numbers of lFLCs are posing a threat to his kidneys, since they appear more sensitive to increasing LC levels than other myeloma patients.
My simple question concerns the relationship between lFLC and creatinine levels. Is there a combination of values that would predict a relapse? Or are the lFLC and creatinine levels inspected separately and judgements made in this way. I'm not talking about horrendous levels of FLCs (many thousands), or creatinine levels that would warrant immediate emergency dialysis. It's the lower, but still very troublesome values that I'm interested in. If anyone has any ideas, I'd be very grateful to hear from you.
Peter
13 posts
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