I am hoping that the collective wisdom here can help me resolve some doubts. I am IgA kappa which means, of course, that my "involved" light chain is kappa. When I started treatment a year ago, my IgA was somewhat elevated and my serum kappa light chain was minimally above normal. My "uninvolved" lambda was normal.
Toward the end of induction treatment, all three immunoglobulin groups (IgA, IgG, and IgM) had dropped to BELOW normal. The kappa and lambda light chains repeatedly still resulted normal, as did the kappa/ lambda ratio. I was particularly pleased about the normal ratio because I had read that a normal K/L ratio indicated a stringent complete response (provided certain other factors, too, were present).
As of my last round of monthly tests, my results are generally normal. My hemoglobin, platelets, white blood cells, red cells, all are within normal ranges. Creatinine is fine; metabolics are fine. However, I continue with the medication-induced hypoglobulinemia and, for the very first time, my "uninvolved" light chain, lambda, has fallen below normal. (My kappa light chain is well within normal.) This has resulted in my kappa/lambda ratio rising to 3.32, the highest it has been since 2009. Big surprise.
What is the significance of the 3.32 K/L ratio for me? Am I no longer in complete remission? At this point I do not have an M-spike and my IFE continues negative. Does the high K/L ratio exclude me from sCR? I should add, in case it is meaningful, that I am on Velcade maintenance every other week and monthly Zometa.
Forums
Re: Low lambda, high kappa/lambda ratio in IgA kappa myeloma
Hi Mrozdav,
First of all, congratulations on the great response you've had to treatment. I hope the rest of your results come in confirming that you've achieved a stringent complete response.
The reason that both your immunoglobulin levels and your uninvolved free light chain levels have gone down to below-normal levels is that, in some (many?) patients, treatment noticeably lowers the level of not just myeloma plasma cells, but also normal, healthy plasma cells.
The normal, healthy plasma cells produce immunoglobulins and free light chains, so if the production of those cells is reduced, well, you get exactly what has happened in your case.
There's a useful forum discussion that occurred late this spring that deals with a situation similar to yours. It includes a very useful table and some links to discussions where some of the Beacon's physician advisors have commented on situations similar to yours:
"Kappa & lambda free light chains down, but ratio up?" (started May 12, 2015)
I think both the above discussion, and the links in it to other discussions, will probably help clear things up for you a lot.
If you still have questions after reading the discussions, post here again, and either I, or someone else, will see if we can help clarify things further.
Again, congrats on the great response you've had to your treatment!
First of all, congratulations on the great response you've had to treatment. I hope the rest of your results come in confirming that you've achieved a stringent complete response.
The reason that both your immunoglobulin levels and your uninvolved free light chain levels have gone down to below-normal levels is that, in some (many?) patients, treatment noticeably lowers the level of not just myeloma plasma cells, but also normal, healthy plasma cells.
The normal, healthy plasma cells produce immunoglobulins and free light chains, so if the production of those cells is reduced, well, you get exactly what has happened in your case.
There's a useful forum discussion that occurred late this spring that deals with a situation similar to yours. It includes a very useful table and some links to discussions where some of the Beacon's physician advisors have commented on situations similar to yours:
"Kappa & lambda free light chains down, but ratio up?" (started May 12, 2015)
I think both the above discussion, and the links in it to other discussions, will probably help clear things up for you a lot.
If you still have questions after reading the discussions, post here again, and either I, or someone else, will see if we can help clarify things further.
Again, congrats on the great response you've had to your treatment!
Re: Low lambda, high kappa/lambda ratio in IgA kappa myeloma
Cheryl G, I really do appreciate your response. I actually saw the table and the discussions you are referring to before posting my inquiry. I found them interesting and informative. What I needed clarification about was the term "monoclonal gammopathy" as applied to persons presenting with normal kappa, low lambda, and high k/l ratio. (See the table.)
I understood that I have bone marrow suppression as evidenced by my below normal immunoglobulins. But do I also have monoclonal gammopathy? I believed this term applied when one of the immunoglobulins was abnormally high and was an indication of detectable myeloma in the serum. Perhaps the term encompasses both low and high level immunoglobulins and both suppressed and elevated light chains? (In which case a high ratio of kappa to lambda would not necessarily indicate the presence of myeloma? I suppose I am just seeking reassurance.)
I gather from subsequent reading that as long as my "involved" kappa level is normal, I am in good shape vis- a- vis my myeloma treatment response. I do, however, wonder whether I need to be seriously concerned about the implications of having suppressed bone marrow. Since I started maintenance, my immunoglobulins have risen somewhat, which I think is a good sign, but they are still below normal.
I very much enjoy reading your responses to other posters. You seem super well informed. You, along with several others, are such wonderful assets to this forum. Thank you again for responding to me and also for the good work you are doing for others who write in with questions.
I understood that I have bone marrow suppression as evidenced by my below normal immunoglobulins. But do I also have monoclonal gammopathy? I believed this term applied when one of the immunoglobulins was abnormally high and was an indication of detectable myeloma in the serum. Perhaps the term encompasses both low and high level immunoglobulins and both suppressed and elevated light chains? (In which case a high ratio of kappa to lambda would not necessarily indicate the presence of myeloma? I suppose I am just seeking reassurance.)
I gather from subsequent reading that as long as my "involved" kappa level is normal, I am in good shape vis- a- vis my myeloma treatment response. I do, however, wonder whether I need to be seriously concerned about the implications of having suppressed bone marrow. Since I started maintenance, my immunoglobulins have risen somewhat, which I think is a good sign, but they are still below normal.
I very much enjoy reading your responses to other posters. You seem super well informed. You, along with several others, are such wonderful assets to this forum. Thank you again for responding to me and also for the good work you are doing for others who write in with questions.
Re: Low lambda, high kappa/lambda ratio in IgA kappa myeloma
Hello mrozdav,
Your reply was very helpful. I think I now see where you are coming from with your questions. It's a bit more subtle than I first realized.
As far as the meaning of "monoclonal gammopathy," it's just shorthand for the group of all three myeloma-related diseases: MGUS, smoldering multiple myeloma, and symptomatic multiple myeloma. I believe the literal meaning of the term is "a disease that causes the presence of monoclonal gamma globulins". There are a couple of other diseases that also can cause monoclonal gammopathy, but, for our purposes, it's really these three diseases that matter.
Before I say anything else, let me emphasize two things.
First, it's always important not to read too much into a single set of test results. The free light chain test, in particular, is measuring really small amounts of protein in the blood, so the results can and do bounce around. And your K/L ratio is only slightly above normal.
Second, given that you just stopped an intensive induction therapy (as I recall, you were being treated with RVD), and have now switched to a less intensive maintenance therapy, your immune system / bone marrow is going through a bit of readjustment. I believe this also can make the results you see less reliable for a few months.
Now, back to your FLC results and what they mean.
In your case, the fact that your "uninvolved" free light chain (FLC) has dipped below normal could be a sign that you're experiencing some bone marrow suppression.
The way I understand it is that, if you were completely healthy and never had multiple myeloma or any other monoclonal gammopathy, bone marrow suppression would cause both the kappa and lambda levels to go down to a similar extent. In that case, your K/L ratio would still be in the normal range.
But because you have kappa as your "involved" free light chain, and because the production of it hasn't been suppressed as much as the production of your lambda FLC, this is a possible sign that you still have enough residual myeloma cells in your body to cause a higher than normal K/L ratio.
Again, I say "possible sign," because this is just a single set of test results, your K/L ratio is just slightly elevated, and your bone marrow is readjusting. You really will need to see what happens with your next few tests to
The bottom line is that I think it is far too early to be worried about this single test result. You want to keep an eye on things, but I would not worry too much.
I hope this makes some sense, and I'm happy to answer any follow-up questions you have. It also would be great if you could keep us posted on what happens going forward, as we all could learn a bit from it.
Finally, I really appreciate your kind words about my posts. I try to be as helpful as I can. I've learned so much from the forum, and that's because so many people have shared their experiences and insights. The least I can do is give a little back. I am also impressed, by the way, with how much you've learned since you first came to the forum, and how you've also started helping people new to the forum. It's really great -- hat tip, kudos, and all that sort of stuff!
Your reply was very helpful. I think I now see where you are coming from with your questions. It's a bit more subtle than I first realized.
As far as the meaning of "monoclonal gammopathy," it's just shorthand for the group of all three myeloma-related diseases: MGUS, smoldering multiple myeloma, and symptomatic multiple myeloma. I believe the literal meaning of the term is "a disease that causes the presence of monoclonal gamma globulins". There are a couple of other diseases that also can cause monoclonal gammopathy, but, for our purposes, it's really these three diseases that matter.
Before I say anything else, let me emphasize two things.
First, it's always important not to read too much into a single set of test results. The free light chain test, in particular, is measuring really small amounts of protein in the blood, so the results can and do bounce around. And your K/L ratio is only slightly above normal.
Second, given that you just stopped an intensive induction therapy (as I recall, you were being treated with RVD), and have now switched to a less intensive maintenance therapy, your immune system / bone marrow is going through a bit of readjustment. I believe this also can make the results you see less reliable for a few months.
Now, back to your FLC results and what they mean.
In your case, the fact that your "uninvolved" free light chain (FLC) has dipped below normal could be a sign that you're experiencing some bone marrow suppression.
The way I understand it is that, if you were completely healthy and never had multiple myeloma or any other monoclonal gammopathy, bone marrow suppression would cause both the kappa and lambda levels to go down to a similar extent. In that case, your K/L ratio would still be in the normal range.
But because you have kappa as your "involved" free light chain, and because the production of it hasn't been suppressed as much as the production of your lambda FLC, this is a possible sign that you still have enough residual myeloma cells in your body to cause a higher than normal K/L ratio.
Again, I say "possible sign," because this is just a single set of test results, your K/L ratio is just slightly elevated, and your bone marrow is readjusting. You really will need to see what happens with your next few tests to
The bottom line is that I think it is far too early to be worried about this single test result. You want to keep an eye on things, but I would not worry too much.
I hope this makes some sense, and I'm happy to answer any follow-up questions you have. It also would be great if you could keep us posted on what happens going forward, as we all could learn a bit from it.
Finally, I really appreciate your kind words about my posts. I try to be as helpful as I can. I've learned so much from the forum, and that's because so many people have shared their experiences and insights. The least I can do is give a little back. I am also impressed, by the way, with how much you've learned since you first came to the forum, and how you've also started helping people new to the forum. It's really great -- hat tip, kudos, and all that sort of stuff!
Re: Low lambda, high kappa/lambda ratio in IgA kappa myeloma
Hi mrozdav and Cheryl G,
Great question, mrozdav, and very good answers, Cheryl G.
I have pretty much the same situation that you describe, mrozdav. And it's been going on for awhile now. I have IgA kappa myeloma, and I achieved sCR and MRD negative status last summer. Up until this week, I've been on Revlimid maintenance since September 2013. (Stopping the Revlimid maintenance is a whole other topic that I will write about in the next few days.)
During most of my my maintenance therapy, my kappa FLC has been normal and the lambda has been normal or somewhat below normal. Sometimes the k/l ratio has been normal, but sometimes it has been slightly high. For the last 3 months, it has been slightly high - 1.90, 2.51, and 1.93.
A couple weeks ago I asked my doctor if the 3 straight months of slightly high ratios indicate that there is some myeloma activity going on. He said it's possible, but also maybe not. He said he would expect the ratio to consistently increase month-to-month if myeloma activity were really going on, but mine is just bouncing around slightly.
Also, since the lambda value is low normal or below normal, any slight change in that can make a significant change in the ratio.
So my doctor is not sure what to make of my wacky k/l ratio at this point. I'll be getting a bone marrow biopsy (BMB) on August 26, so maybe we'll get a little more data to help understand things then. Obviously, I'm hoping for continued MRD negative!
Finally, I'd like to second what mrozdav said about your contributions to the Forum, Cheryl G. Thanks for all the insights you've provided us!
Mike
Great question, mrozdav, and very good answers, Cheryl G.
I have pretty much the same situation that you describe, mrozdav. And it's been going on for awhile now. I have IgA kappa myeloma, and I achieved sCR and MRD negative status last summer. Up until this week, I've been on Revlimid maintenance since September 2013. (Stopping the Revlimid maintenance is a whole other topic that I will write about in the next few days.)
During most of my my maintenance therapy, my kappa FLC has been normal and the lambda has been normal or somewhat below normal. Sometimes the k/l ratio has been normal, but sometimes it has been slightly high. For the last 3 months, it has been slightly high - 1.90, 2.51, and 1.93.
A couple weeks ago I asked my doctor if the 3 straight months of slightly high ratios indicate that there is some myeloma activity going on. He said it's possible, but also maybe not. He said he would expect the ratio to consistently increase month-to-month if myeloma activity were really going on, but mine is just bouncing around slightly.
Also, since the lambda value is low normal or below normal, any slight change in that can make a significant change in the ratio.
So my doctor is not sure what to make of my wacky k/l ratio at this point. I'll be getting a bone marrow biopsy (BMB) on August 26, so maybe we'll get a little more data to help understand things then. Obviously, I'm hoping for continued MRD negative!
Finally, I'd like to second what mrozdav said about your contributions to the Forum, Cheryl G. Thanks for all the insights you've provided us!
Mike
-
mikeb - Name: mikeb
- Who do you know with myeloma?: self
- When were you/they diagnosed?: 2009 (MGUS at that time)
- Age at diagnosis: 55
Re: Low lambda, high kappa/lambda ratio in IgA kappa myeloma
Cheryl G and mikeb, This has been incredibly helpful. I hesitated about writing initially, but now am glad that I did. Mike, please let me know whatever more you learn about this k/l situation in the coming weeks. Best of luck on your upcoming BMB.
Re: Low lambda, high kappa/lambda ratio in IgA kappa myeloma
Thanks, mikeb, for that extra information. It was very helpful. Based on what your myeloma specialist said, it seems like we were on the right path with what we had been discussing earlier in the thread. But it's really helpful to learn what you've been told about a very similar situation.
Thanks also for your kind words. I am happy to return the favor by saying that I always look forward to reading your postings. They always provide a lot of relevant experience and insight.
Thanks also for your kind words. I am happy to return the favor by saying that I always look forward to reading your postings. They always provide a lot of relevant experience and insight.
Re: Low lambda, high kappa/lambda ratio in IgA kappa myeloma
This has been an interesting thread, and I'll add my thanks to Cheryl, Multibilly, and others who have posted valuable explanations here and in the preceding threads
"Kappa & lambda free light chains down, but ratio up?" (started May 12, 2015)
"Kappa FLC fluctuations in lambda light chain myeloma" (started May 5, 2015)
There are a couple of important points that I have not seen mentioned in these threads. Understanding these might help to make sense of the test results and to appreciate their limitations. So I'll make an attempt to cover them here..
A person who doesn't have myeloma has many kinds of immunoglobulin molecules (a.k.a. antibodies) circulating in the blood. Each has a heavy-chain part and a light chain part. There are 10 isotypes covering all combinations of the 5 types of heavy chain and two types of light chain. The (normal) plasma cells make more of the light chain parts than the heavy chain parts, so there are also some "free" light chains (the extra ones) in the plasma. But each person has *millions* of different kinds of immunoglobulins, not just 10 kinds! There is one for each kind of infection to which the person has acquired some immunity. The isotypes specify only the top-level gross structure of the molecules, but there are differences in the small details, and these determine which antigen a particular immunoglobulin binds to. So, although a set of molecules might all be of the same isotype (say, IgG-lambda), they are not all the same.
Each plasma cell produces only one of these millions of versions, so there are millions of different plasma cells in all of us. But the myeloma cells (cancerous plasma cells) are pretty much all the same, so they produce immunoglobulins that are *exactly* the same – not just the same isotype, but also identical in their small details. We say that the myeloma cells are "monoclonal" – all clones of one original cancerous cell. (Actually, in myeloma there can be several different clones, but that's a detail for another time.) The normal plasma cells are said to be "polyclonal". The immunoglobulin produced by the myeloma cells are said to be a "monoclonal protein" or "M protein". Most of the time, the myeloma cells produce extras of the light chain parts of their M protein (just like normal plasma cells), and those circulate in the blood as free light chains, Those light chains also monoclonal – not just all kappa or all lambda, but all exactly the same. It is this distinction between monoclonal and polyclonal proteins that was missing from the preceding discussions.
This brings us finally to the original subject: interpreting the free light chain measurements. The serum free light chain assay tells us the total concentration and kappa and lambda FLCs in the serum, but it does not distinguish polyclonal from monoclonal. The same is true of the quantitative immunoglobulin tests (which measure the concentrations of the complete immunoglobulin molecules separately for each heavy-chain part – IgG, IgA, and IgM are usually measured for myeloma patients). These tests give the total concentration of each type, but they don't distinguish monoclonal from polyclonal. So a lot of what's measured is normal, and only part of it is due to the cancer. What we really want to know is how much is monoclonal, since that's a measure of the activity of the cancer.
The reason that the light chain test is useful is that normally the concentration of both kappa and lambda is pretty small. So if one or the other is several times normal then it's a pretty good bet that a lot of it is due to the cancer. Nevertheless, we don't directly know. There are other things that can affect those concentrations, as detailed in this chart from The Binding Site replicated here in the forum.
If you look at each one to see whether it's high or low, as well as looking at the ratio, you have pretty good shot at figuring out what's going on.
Nevertheless, there are ways to find the concentration of just the monoclonal immunoglobulins. The best-known is serum protein electrophoresis (SPEP), which separates all the proteins in the serum by size and charge, enabling the lab to see if there are a lot that are all the same. This is the "M spike" on the SPEP tracing, and it allows the concentration of M protein to be measured. The trouble is that this test is not very sensitive, so a patient who has responded well to treatment may still have some myeloma cells that are producing M protein, but it is not enough to be detectable on the SPEP test. We say that such a patient is in CR, but the myeloma is not necessarily gone.
For a patient in CR, the SFLC test can help to track the disease because it is more sensitive. But it is not foolproof, as the earlier postings in this thread have shown. That's because it is not directly measuring the monoclonal (or abnormal or cancer-produced) FLCs, just the total of normal and abnormal for each type.
There is another test that can distinguish monoclonal from polyclonal proteins. It is very similar to SPEP, but more sensitive. It's called immunofixation electrophoresis. It's similar to SPEP, but after separating the proteins by size and charge, an antigen that binds to a particular heavy-chain type or light-chain type is added, causing a detectable precipitate. If a lot of precipitate occurs over a narrow range of size/charge, it is likely due to monoclonal protein. This is done separately for IgG, IgA, IgM, lambda, and kappa, so the isotype of the monoclonal protein is also determined. The disadvantage of this test is that, unlike SPEP, it does not give the quantity of M protein, just whether it is present. The advantage is that it can find some M protein when there is not enough to be detected by SPEP.
Well, maybe that's enough. I hope this will be helpful to some people.
Best wishes,
Larry
"Kappa & lambda free light chains down, but ratio up?" (started May 12, 2015)
"Kappa FLC fluctuations in lambda light chain myeloma" (started May 5, 2015)
There are a couple of important points that I have not seen mentioned in these threads. Understanding these might help to make sense of the test results and to appreciate their limitations. So I'll make an attempt to cover them here..
A person who doesn't have myeloma has many kinds of immunoglobulin molecules (a.k.a. antibodies) circulating in the blood. Each has a heavy-chain part and a light chain part. There are 10 isotypes covering all combinations of the 5 types of heavy chain and two types of light chain. The (normal) plasma cells make more of the light chain parts than the heavy chain parts, so there are also some "free" light chains (the extra ones) in the plasma. But each person has *millions* of different kinds of immunoglobulins, not just 10 kinds! There is one for each kind of infection to which the person has acquired some immunity. The isotypes specify only the top-level gross structure of the molecules, but there are differences in the small details, and these determine which antigen a particular immunoglobulin binds to. So, although a set of molecules might all be of the same isotype (say, IgG-lambda), they are not all the same.
Each plasma cell produces only one of these millions of versions, so there are millions of different plasma cells in all of us. But the myeloma cells (cancerous plasma cells) are pretty much all the same, so they produce immunoglobulins that are *exactly* the same – not just the same isotype, but also identical in their small details. We say that the myeloma cells are "monoclonal" – all clones of one original cancerous cell. (Actually, in myeloma there can be several different clones, but that's a detail for another time.) The normal plasma cells are said to be "polyclonal". The immunoglobulin produced by the myeloma cells are said to be a "monoclonal protein" or "M protein". Most of the time, the myeloma cells produce extras of the light chain parts of their M protein (just like normal plasma cells), and those circulate in the blood as free light chains, Those light chains also monoclonal – not just all kappa or all lambda, but all exactly the same. It is this distinction between monoclonal and polyclonal proteins that was missing from the preceding discussions.
This brings us finally to the original subject: interpreting the free light chain measurements. The serum free light chain assay tells us the total concentration and kappa and lambda FLCs in the serum, but it does not distinguish polyclonal from monoclonal. The same is true of the quantitative immunoglobulin tests (which measure the concentrations of the complete immunoglobulin molecules separately for each heavy-chain part – IgG, IgA, and IgM are usually measured for myeloma patients). These tests give the total concentration of each type, but they don't distinguish monoclonal from polyclonal. So a lot of what's measured is normal, and only part of it is due to the cancer. What we really want to know is how much is monoclonal, since that's a measure of the activity of the cancer.
The reason that the light chain test is useful is that normally the concentration of both kappa and lambda is pretty small. So if one or the other is several times normal then it's a pretty good bet that a lot of it is due to the cancer. Nevertheless, we don't directly know. There are other things that can affect those concentrations, as detailed in this chart from The Binding Site replicated here in the forum.
If you look at each one to see whether it's high or low, as well as looking at the ratio, you have pretty good shot at figuring out what's going on.
Nevertheless, there are ways to find the concentration of just the monoclonal immunoglobulins. The best-known is serum protein electrophoresis (SPEP), which separates all the proteins in the serum by size and charge, enabling the lab to see if there are a lot that are all the same. This is the "M spike" on the SPEP tracing, and it allows the concentration of M protein to be measured. The trouble is that this test is not very sensitive, so a patient who has responded well to treatment may still have some myeloma cells that are producing M protein, but it is not enough to be detectable on the SPEP test. We say that such a patient is in CR, but the myeloma is not necessarily gone.
For a patient in CR, the SFLC test can help to track the disease because it is more sensitive. But it is not foolproof, as the earlier postings in this thread have shown. That's because it is not directly measuring the monoclonal (or abnormal or cancer-produced) FLCs, just the total of normal and abnormal for each type.
There is another test that can distinguish monoclonal from polyclonal proteins. It is very similar to SPEP, but more sensitive. It's called immunofixation electrophoresis. It's similar to SPEP, but after separating the proteins by size and charge, an antigen that binds to a particular heavy-chain type or light-chain type is added, causing a detectable precipitate. If a lot of precipitate occurs over a narrow range of size/charge, it is likely due to monoclonal protein. This is done separately for IgG, IgA, IgM, lambda, and kappa, so the isotype of the monoclonal protein is also determined. The disadvantage of this test is that, unlike SPEP, it does not give the quantity of M protein, just whether it is present. The advantage is that it can find some M protein when there is not enough to be detected by SPEP.
Well, maybe that's enough. I hope this will be helpful to some people.
Best wishes,
Larry
-
LarryD - Name: Larry D'Addario
- Who do you know with myeloma?: wife
- When were you/they diagnosed?: September 2012
- Age at diagnosis: 65
Re: Low lambda, high kappa/lambda ratio in IgA kappa myeloma
Hi Larry,
Thanks for pointing out that the potential value of the serum immunofixation test in situations similar to this one.
In the case of Mrozdav and Mikeb, however, both have achieved a stringent complete response. To achieve either a complete response or a stringent complete response, the patient has to have no sign of a monoclonal protein on the serum immunofixation test. So the concern in this situation is whether, despite a negative immunofixation result and normal kappa and lambda levels, the abnormal kappa-lambda ratio may be signalling signs of low-level myeloma activity.
So the immunofixation test isn't really going to clarify things in this situation.
One possibility that I considered after reading this discussion, and which hasn't been mentioned so far, is to have is to have a Hevylite test performed. As Cheryl G excellently described in this forum posting, the Hevylite assay measures a patient's levels of each of the 10 different heavy-chain / light-chain immunoglobulin isotypes (IgG kappa, IgG lambda, IgA kappa, IgA lambda, etc.). So, in Mrozdav's case, it would be able to say whether her IgA kappa – her "involved" isotype – is elevated.
However, in reading up about the test, it's not clear to me that it has been proven to be more sensitive than the immunofixation test in picking up on any monoclonal immunoglobulins that may be present. It appears to be at least as sensitive as the immunofixation test, but I'm not sure there is conclusive evidence that it is more sensitive.
Note, though, that the Freelite serum free light chain assay is believed to be more sensitive than the immunofixation test in detecting monoclonal free light chains (even though it measures total free light chains -- monoclonal and polyclonal -- in the blood). See Figure 2 in this document [PDF file; may download instead of loading into browser].
So I think that Mrozdav and Mikeb have been doing the right thing by asking whether their free light chain tests are signalling something to be concerned about.
Thanks for pointing out that the potential value of the serum immunofixation test in situations similar to this one.
In the case of Mrozdav and Mikeb, however, both have achieved a stringent complete response. To achieve either a complete response or a stringent complete response, the patient has to have no sign of a monoclonal protein on the serum immunofixation test. So the concern in this situation is whether, despite a negative immunofixation result and normal kappa and lambda levels, the abnormal kappa-lambda ratio may be signalling signs of low-level myeloma activity.
So the immunofixation test isn't really going to clarify things in this situation.
One possibility that I considered after reading this discussion, and which hasn't been mentioned so far, is to have is to have a Hevylite test performed. As Cheryl G excellently described in this forum posting, the Hevylite assay measures a patient's levels of each of the 10 different heavy-chain / light-chain immunoglobulin isotypes (IgG kappa, IgG lambda, IgA kappa, IgA lambda, etc.). So, in Mrozdav's case, it would be able to say whether her IgA kappa – her "involved" isotype – is elevated.
However, in reading up about the test, it's not clear to me that it has been proven to be more sensitive than the immunofixation test in picking up on any monoclonal immunoglobulins that may be present. It appears to be at least as sensitive as the immunofixation test, but I'm not sure there is conclusive evidence that it is more sensitive.
Note, though, that the Freelite serum free light chain assay is believed to be more sensitive than the immunofixation test in detecting monoclonal free light chains (even though it measures total free light chains -- monoclonal and polyclonal -- in the blood). See Figure 2 in this document [PDF file; may download instead of loading into browser].
So I think that Mrozdav and Mikeb have been doing the right thing by asking whether their free light chain tests are signalling something to be concerned about.
Re: Low lambda, high kappa/lambda ratio in IgA kappa myeloma
mrozdav,
Like you and other responders to your post, I am also seeing a lot of bone marrow suppression while I am being treated for relapsed myeloma with Velcade. I also saw bone marrow suppression while I was on Revlimid maintenance therapy. As the others have said already, the drugs used to treat myeloma are not so selective that they only target or affect cancerous plasma cells, so I am not surprised by the results I see in my blood work and feel they can be expected.
I believe while undergoing treatment with these drugs you really cannot make a meaningful comparison to what is considered to be normal ranges and implied prognosis when taking these drugs. These is where the experience of the oncologist is need to put context and meaning for what lab results indicated for the individual patient given their situation and treatment at that moment in time.
I have IgG kappa myeloma and earlier this year I was getting a bit concerned and excited about my light chain ratio rising up in the teens and my kappa protein values getting into the low 20s to 40s. Then, when relapse really kicked in, my kappa light chain soared up to 3040 pretty quickly, while my lambda light chain value dropped to 1 from bone marrow suppression with my first cycle of Velcade. So my kappa / lambda ratio was 3040. Suddenly, a kappa / lambda light chain ratio in the teens did not look so bad, I have learned that I have to keeps things in context.
The one concern I do have is with any bone marrow suppression for whatever reason, the immune system can be suppressed. So being aware of this and take precautions to try and avoid getting sick, especially to the point where treatment needs to be stopped to recover. This has happened to me several times over the last few years.
Best wishes,
Eric
Like you and other responders to your post, I am also seeing a lot of bone marrow suppression while I am being treated for relapsed myeloma with Velcade. I also saw bone marrow suppression while I was on Revlimid maintenance therapy. As the others have said already, the drugs used to treat myeloma are not so selective that they only target or affect cancerous plasma cells, so I am not surprised by the results I see in my blood work and feel they can be expected.
I believe while undergoing treatment with these drugs you really cannot make a meaningful comparison to what is considered to be normal ranges and implied prognosis when taking these drugs. These is where the experience of the oncologist is need to put context and meaning for what lab results indicated for the individual patient given their situation and treatment at that moment in time.
I have IgG kappa myeloma and earlier this year I was getting a bit concerned and excited about my light chain ratio rising up in the teens and my kappa protein values getting into the low 20s to 40s. Then, when relapse really kicked in, my kappa light chain soared up to 3040 pretty quickly, while my lambda light chain value dropped to 1 from bone marrow suppression with my first cycle of Velcade. So my kappa / lambda ratio was 3040. Suddenly, a kappa / lambda light chain ratio in the teens did not look so bad, I have learned that I have to keeps things in context.
The one concern I do have is with any bone marrow suppression for whatever reason, the immune system can be suppressed. So being aware of this and take precautions to try and avoid getting sick, especially to the point where treatment needs to be stopped to recover. This has happened to me several times over the last few years.
Best wishes,
Eric
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Eric Hofacket - Name: Eric H
- When were you/they diagnosed?: 01 April 2011
- Age at diagnosis: 44
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