My name is Mort and this is my first submission to the Beacon forum. I was first diagnosed as having MGUS with M-protein of about 1.0 g/dL in July 2008.
At age 90, I appear to be asymptomatic, and my last four M-protein determinations, at roughly 6-month intervals, were 2.11, 2.08, 1.99 and, just two weeks ago, 2.05 g/dL. An IFE assay in 2010 indicated I was IgG kappa. However, I just learned from my hematologist that my kappa / lambda ratio (FLC) this month was found to be 72, which puts me in the class of having two of three risk factors (M-protein greater than 1.5 g/dL and abnormal FLC ratio).
Given my age, and being that I apparently am in otherwise good health, am I likely to not progress to myeloma but eventually succumb to something else? From this article,
SV Rajkumar et al, "Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance," Blood, 2005 (full text of article)
I draw the impression that my risk of progression to myeloma is, in one example, 17% at 10 years, and, in another example, 37% at 20 years, even taking into account my rather high FLC ratio. Thus, with reservation, I am led to believe that at my age I may well avoid progressing to myeloma.
Forums
Re: Risk of progression from MGUS to multiple myeloma
Hi Mort,
What was your free light chain (FLC) ratio before your most recent test? You say your latest serum FLC ratio of 72 now qualifies as an additional Mayo MGUS risk-of-progression factor, but you imply that your serum FLC ratio was normal before. But if that is the case and your serum FLC ratio moved from being normal (> 0.26 and <1.65) to 72, then that is a very large jump.
If your serum FLC ratio indeed moved this much between tests, I might question whether your serum free light chain results were accurate and ask to be re-tested now (or at least within the next couple of months).
What was your free light chain (FLC) ratio before your most recent test? You say your latest serum FLC ratio of 72 now qualifies as an additional Mayo MGUS risk-of-progression factor, but you imply that your serum FLC ratio was normal before. But if that is the case and your serum FLC ratio moved from being normal (> 0.26 and <1.65) to 72, then that is a very large jump.
If your serum FLC ratio indeed moved this much between tests, I might question whether your serum free light chain results were accurate and ask to be re-tested now (or at least within the next couple of months).
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Risk of progression from MGUS to multiple myeloma
Thank you for your well-taken comments, Multibilly.
As it happens, I was first informed that I had IgG kappa back in 2010. At that time, however, a qualitative band of kappa light chains in one tube was shown in the report plus another tube that was empty of any lambda light chains. This qualitative picture suggests that the kappa/lambda ratio was "infinity." There could have been some tiny amount of lambda present, yielding a high, abnormal FLC ratio, more or less compatible with my current abnormal ratio of 72.
Clearly, my hematologist plans to redetermine the FLC ratio in 3-4 months. My concern is that since my M-spike is 2.05 g/dL (most recent values at 6-month intervals: 2.12, 2.08, and previously, 1.99), with normal calcium, creatinine and indeterminate C-reactive protein, and otherwise asymptomatic, am I still in MGUS, and hence not likely to progress to multiple myeloma in the next few years?
As it happens, I was first informed that I had IgG kappa back in 2010. At that time, however, a qualitative band of kappa light chains in one tube was shown in the report plus another tube that was empty of any lambda light chains. This qualitative picture suggests that the kappa/lambda ratio was "infinity." There could have been some tiny amount of lambda present, yielding a high, abnormal FLC ratio, more or less compatible with my current abnormal ratio of 72.
Clearly, my hematologist plans to redetermine the FLC ratio in 3-4 months. My concern is that since my M-spike is 2.05 g/dL (most recent values at 6-month intervals: 2.12, 2.08, and previously, 1.99), with normal calcium, creatinine and indeterminate C-reactive protein, and otherwise asymptomatic, am I still in MGUS, and hence not likely to progress to multiple myeloma in the next few years?
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Mort - Name: Morton Golub
- When were you/they diagnosed?: MGUS - July 2008
- Age at diagnosis: 83
Re: Risk of progression from MGUS to multiple myeloma
Mort,
Regarding "am I still MGUS?":
You are asymptomatic since I take it that you do not meet one or more CRAB criteria (hypercalcemia, renal impairment, anemia, or bone involvement) and that your doctor is on top of all the tests to screen for meeting the CRAB criteria.
Based on what you said, you would still be classified as having MGUS UNLESS a new bone marrow test showed greater than 10% bone marrow plasma cells (BMPC %) or your M-spike was > 3 g/dL. If one of these M-spike or BMPC% events did happen, you would then be classified as having smoldering multiple myeloma instead of MGUS, assuming you still did not meet one or more of the CRAB criteria. But keep in mind that smoldering multiple myeloma is still an asymptomatic diagnosis.
The only other wild cards are the the new "myeloma defining event" (MDE) criteria (see below). If your future FLC test shows an FLC ratio > 100 AND a kappa FLC > 100 mg/L, then you would technically have an MDE. But having an MDE still does not mean you are symptomatic, only that a doc "may" consider starting treatment (noting that not all specialists agree with considering starting treatment based on a patient developing an MDE). Also, at age 90, I'm not sure that a specialist would consider starting treatment even if you did develop an MDE. But that's something for you to discuss with your doc.
SV Rajkumar, "New Criteria For The Diagnosis Of Multiple Myeloma And Related Disorders," The Myeloma Beacon, Oct 26, 2014
Regarding "am I still MGUS?":
You are asymptomatic since I take it that you do not meet one or more CRAB criteria (hypercalcemia, renal impairment, anemia, or bone involvement) and that your doctor is on top of all the tests to screen for meeting the CRAB criteria.
Based on what you said, you would still be classified as having MGUS UNLESS a new bone marrow test showed greater than 10% bone marrow plasma cells (BMPC %) or your M-spike was > 3 g/dL. If one of these M-spike or BMPC% events did happen, you would then be classified as having smoldering multiple myeloma instead of MGUS, assuming you still did not meet one or more of the CRAB criteria. But keep in mind that smoldering multiple myeloma is still an asymptomatic diagnosis.
The only other wild cards are the the new "myeloma defining event" (MDE) criteria (see below). If your future FLC test shows an FLC ratio > 100 AND a kappa FLC > 100 mg/L, then you would technically have an MDE. But having an MDE still does not mean you are symptomatic, only that a doc "may" consider starting treatment (noting that not all specialists agree with considering starting treatment based on a patient developing an MDE). Also, at age 90, I'm not sure that a specialist would consider starting treatment even if you did develop an MDE. But that's something for you to discuss with your doc.
SV Rajkumar, "New Criteria For The Diagnosis Of Multiple Myeloma And Related Disorders," The Myeloma Beacon, Oct 26, 2014
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Risk of progression from MGUS to multiple myeloma
Thanks again, Multibilly for your informative remarks regarding free light chain ratios.
As Dr. Rajkumar noted in the article you cited, a "myeloma-defining event" is one where the serum involved / uninvolved free light chain ratio is 100 or more, provided the absolute value of the involved free light chain is at least 100 mg/L. My question, now: How serious should I regard my free light chain ratio of 72, when my absolute value for kappa was 704.81 mg/L (well above the threshold of 100 mg/L) and for lambda was 9.75 mg/L?
I still consider myself in MGUS given that my M-protein remains around 2 g/dL (20 g/L). (The last four measurements at 6-month intervals were 2.12, 2.08, 1.99 and, most recently, 2.05 g/dL.) I appear to be otherwise asymptomatic and seemingly without CRAB criteria. I was first diagnosed as having MGUS in July 2008.
No doubt, my hematologist will recommend additional tests at the next visit, when I will be having my first UPEP.
As Dr. Rajkumar noted in the article you cited, a "myeloma-defining event" is one where the serum involved / uninvolved free light chain ratio is 100 or more, provided the absolute value of the involved free light chain is at least 100 mg/L. My question, now: How serious should I regard my free light chain ratio of 72, when my absolute value for kappa was 704.81 mg/L (well above the threshold of 100 mg/L) and for lambda was 9.75 mg/L?
I still consider myself in MGUS given that my M-protein remains around 2 g/dL (20 g/L). (The last four measurements at 6-month intervals were 2.12, 2.08, 1.99 and, most recently, 2.05 g/dL.) I appear to be otherwise asymptomatic and seemingly without CRAB criteria. I was first diagnosed as having MGUS in July 2008.
No doubt, my hematologist will recommend additional tests at the next visit, when I will be having my first UPEP.
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Mort - Name: Morton Golub
- When were you/they diagnosed?: MGUS - July 2008
- Age at diagnosis: 83
Re: Risk of progression from MGUS to multiple myeloma
Mort,
I don't think there's an easy answer for what your current free light chain numbers portend. But I would be keeping a sharp eye on my kidney function.
If it were me, I would first be going back and graphing my kappa and lambda free light chain levels and kappa-lambda ratio to see what sort of a trajectory they were on.
But even if I knew all of the details of my free light chain history and associated trends, the fundamental question still remains: "So what if my free light chain ratio hits 100 (or more) and I still have no CRAB issues?"
You need to ask yourself (and your specialist) if you would start treatment based on only test results with no indication of end organ damage, especially considering your age. Statistically, the reason the IMWG selected an free light chain ratio of 100 to be a "myeloma defining event" is because some studies showed that something like 80% (I'm recalling this number of the top of my head) of folks with a free light chain ratio of 100 (and involved free light chain level > 100 mg/L) progressed to symptomatic multiple myeloma within two years.
But that also means that the remainder of the patients did not progress in that same time, and that some doctors are now treating smoldering patients without the benefit of any long-term clinical trial results that compares the overall survival and progression-free survival stats of treating and not treating patients with "myeloma defining events".
In any case, it's a very personal decision as to whether you would want to consider treatment based on developing a myeloma defining event in the absence of organ damage. What I do know is that, at least for me, there is no perfect or correct answer in this situation. This is also the sort of situation where you need to know that you both respect and implicitly trust the specialist you are working with to help guide you through this kind of choice ... should you be faced with it.
I don't think there's an easy answer for what your current free light chain numbers portend. But I would be keeping a sharp eye on my kidney function.
If it were me, I would first be going back and graphing my kappa and lambda free light chain levels and kappa-lambda ratio to see what sort of a trajectory they were on.
But even if I knew all of the details of my free light chain history and associated trends, the fundamental question still remains: "So what if my free light chain ratio hits 100 (or more) and I still have no CRAB issues?"
You need to ask yourself (and your specialist) if you would start treatment based on only test results with no indication of end organ damage, especially considering your age. Statistically, the reason the IMWG selected an free light chain ratio of 100 to be a "myeloma defining event" is because some studies showed that something like 80% (I'm recalling this number of the top of my head) of folks with a free light chain ratio of 100 (and involved free light chain level > 100 mg/L) progressed to symptomatic multiple myeloma within two years.
But that also means that the remainder of the patients did not progress in that same time, and that some doctors are now treating smoldering patients without the benefit of any long-term clinical trial results that compares the overall survival and progression-free survival stats of treating and not treating patients with "myeloma defining events".
In any case, it's a very personal decision as to whether you would want to consider treatment based on developing a myeloma defining event in the absence of organ damage. What I do know is that, at least for me, there is no perfect or correct answer in this situation. This is also the sort of situation where you need to know that you both respect and implicitly trust the specialist you are working with to help guide you through this kind of choice ... should you be faced with it.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Risk of progression from MGUS to multiple myeloma
Mort,
Have you had a PET/CT scan? Based on all your other tests, if the PET/CT scan doesn't show any activity, I certainly would NOT start any treatments.
Good Luck,
Coach Hoke
Have you had a PET/CT scan? Based on all your other tests, if the PET/CT scan doesn't show any activity, I certainly would NOT start any treatments.
Good Luck,
Coach Hoke
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coachhoke - Name: coachhoke
- When were you/they diagnosed?: Apri 2012
- Age at diagnosis: 71
Re: Risk of progression from MGUS to multiple myeloma
This is Mort again reporting on blood results of August 13, 2016 as a follow-up to prior results of March 16, 2016 reported in my first posting in this thread. Before launching into my new results, I would like to again express my appreciation to Multibilly for his astute comments to my several postings on the above subject.
In some ways, I am pleased with the latest results. Thus, for example, for the first time in eight years since first diagnosed with MGUS, four of the five critical components of blood (RBC, WBC, HGB and HCT) were all in the normal range; platelets, in contrast, were well below the normal range, but essentially the same as previously (113.0 vs. 115.0 10-cubed/uL).
With hemoglobin now normal, I believe that disposes of the 'A' in the CRAB criteria.
Likewise, both creatinine and BUN being normal suggests that the 'R' in CRAB may be dismissed. Similarly, with calcium level being normal, I believe we can disregard the 'C' in CRAB.
Since I am asymptomatic, I am currently of the view that the 'B' for 'bone' in CRAB is not a factor. On that point, my hematologist/oncologist has requested I submit to a whole-body PET/CT scan, which should answer the question re 'B', and also to a bone-marrow biopsy to indicate if the MGUS is slowly advancing to a malignant condition.
Another favorable result is my C-reactive protein which has remained constant at the rather low value of less than 0.1 mg/dL.
For the last several years my M-protein has been at around 2.0 g/dL (20 g/l), and the latest result shows a small decrease from the previous value of 2.05 to 1.97 g/dL which makes me believe that I am still in MGUS, though as pointed out previously, I face the prospect of a potential 'myeloma defining event' (MDE) because of a high value for my free light chain (FLC) ratio.
Some of the latest results are disappointing. Thus, beta-2-microglobulin rose from a normal value of 2.03 mg/L previously to an above-normal value of 2.38 mg/L. Here, it may be noted that the lab report stated "Results (for this compound) cannot be interpreted as absolute evidence of the presence or absence of malignant disease."
What appears more serious is the FLC kappa-lambda ratio, which increased from 72.29 to 78.69, suggesting that it may be on the course to reach in time the threshold of 100 which is associated with a "myeloma-defining event" (MDE). I am heartened to have read a comment by Aramis in this forum thread to the effect that he has an M-spike of 1.2 g/dL, and FLC ratios of 360 and higher, with FLC levels well over 100 for nearly 7 years, with no ill effects and no Bence-Jones protein in urine.
So, I am still in a quandary: Am I still in MGUS, and what is the likelihood for this 91-year old retired male to ever experience multiple myeloma?
In some ways, I am pleased with the latest results. Thus, for example, for the first time in eight years since first diagnosed with MGUS, four of the five critical components of blood (RBC, WBC, HGB and HCT) were all in the normal range; platelets, in contrast, were well below the normal range, but essentially the same as previously (113.0 vs. 115.0 10-cubed/uL).
With hemoglobin now normal, I believe that disposes of the 'A' in the CRAB criteria.
Likewise, both creatinine and BUN being normal suggests that the 'R' in CRAB may be dismissed. Similarly, with calcium level being normal, I believe we can disregard the 'C' in CRAB.
Since I am asymptomatic, I am currently of the view that the 'B' for 'bone' in CRAB is not a factor. On that point, my hematologist/oncologist has requested I submit to a whole-body PET/CT scan, which should answer the question re 'B', and also to a bone-marrow biopsy to indicate if the MGUS is slowly advancing to a malignant condition.
Another favorable result is my C-reactive protein which has remained constant at the rather low value of less than 0.1 mg/dL.
For the last several years my M-protein has been at around 2.0 g/dL (20 g/l), and the latest result shows a small decrease from the previous value of 2.05 to 1.97 g/dL which makes me believe that I am still in MGUS, though as pointed out previously, I face the prospect of a potential 'myeloma defining event' (MDE) because of a high value for my free light chain (FLC) ratio.
Some of the latest results are disappointing. Thus, beta-2-microglobulin rose from a normal value of 2.03 mg/L previously to an above-normal value of 2.38 mg/L. Here, it may be noted that the lab report stated "Results (for this compound) cannot be interpreted as absolute evidence of the presence or absence of malignant disease."
What appears more serious is the FLC kappa-lambda ratio, which increased from 72.29 to 78.69, suggesting that it may be on the course to reach in time the threshold of 100 which is associated with a "myeloma-defining event" (MDE). I am heartened to have read a comment by Aramis in this forum thread to the effect that he has an M-spike of 1.2 g/dL, and FLC ratios of 360 and higher, with FLC levels well over 100 for nearly 7 years, with no ill effects and no Bence-Jones protein in urine.
So, I am still in a quandary: Am I still in MGUS, and what is the likelihood for this 91-year old retired male to ever experience multiple myeloma?
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Mort - Name: Morton Golub
- When were you/they diagnosed?: MGUS - July 2008
- Age at diagnosis: 83
Re: Risk of progression from MGUS to multiple myeloma
Hi Mort,
A couple of points.
My local onc is one of those physicians mentioned in the link below that doesn't put a lot of stock in using beta2 microglobulin (B2M) to track progression of multiple myeloma. He states that too many things can affect one's B2M to really make it useful at my stage (smoldering).
https://myelomabeacon.org/forum/rising-beta-2-microglobulin-t6191.html#p37301
I'm not a doc, but the relatively small difference in your FLC ratio readings could easily be attributable to normal fluctuations in your FLC values and/or differences in lab equipment. My FLC ratio readings have bounced all the over place.
https://myelomabeacon.org/forum/fenofibrate-tricor-and-multiple-myeloma-t2690-50.html#p41916
So, I think my earlier comments still apply regarding the question as to whether you are still at the MGUS stage.
https://myelomabeacon.org/forum/risk-of-progression-mgus-multiple-myeloma-t6976.html#p41990
The PET/CT results will answer the 'B" in CRAB question from a lytic lesion standpoint. But you would need a DEXA scan to rule out osteopenia/osteoporosis (either of which can also fulfill the "B" in CRAB criteria).
A couple of points.
My local onc is one of those physicians mentioned in the link below that doesn't put a lot of stock in using beta2 microglobulin (B2M) to track progression of multiple myeloma. He states that too many things can affect one's B2M to really make it useful at my stage (smoldering).
https://myelomabeacon.org/forum/rising-beta-2-microglobulin-t6191.html#p37301
I'm not a doc, but the relatively small difference in your FLC ratio readings could easily be attributable to normal fluctuations in your FLC values and/or differences in lab equipment. My FLC ratio readings have bounced all the over place.
https://myelomabeacon.org/forum/fenofibrate-tricor-and-multiple-myeloma-t2690-50.html#p41916
So, I think my earlier comments still apply regarding the question as to whether you are still at the MGUS stage.
https://myelomabeacon.org/forum/risk-of-progression-mgus-multiple-myeloma-t6976.html#p41990
The PET/CT results will answer the 'B" in CRAB question from a lytic lesion standpoint. But you would need a DEXA scan to rule out osteopenia/osteoporosis (either of which can also fulfill the "B" in CRAB criteria).
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Risk of progression from MGUS to multiple myeloma
This is Mort again reporting belatedly on results of 24-hour urine analyses of August 3, 2016 and on PET/CT scans performed on September 21, 2016.
Protein in urine: 320 mg/24 hr, which translated to 32 mg/dL (since total volume of urine: 1000 mL).
This number contrasts with 80.1 mg/dL kappa free light chain level in the blood, reported previously.
"Urine Immunofixation Pattern Interpretation: Two free kappa paraprotein peaks detected."
In reporting this result on the phone, my onc gave me the impression that this was not surprising given the appearance of a fair amount of kappa free light chains in the blood.
The PET/CT scans strengthen my view that the "B" in the "CRAB" criteria can be disregarded, in accord with my earlier view based on my being asymptomatic. I quote the specific findings in the radiology report:
"There is no evidence of hypermetabolic osseous lesions within the visualized axial and appendicular skeleton. The Coregistered CT scan did not reveal any osteolytic destructive lesions."
"There was no focal pulmonary parenchymal hypermetabolic abnormality. The liver ... without focal intrinsic abnormality. ... no enlarged or hypermetabolic lymph nodes ... no hypermetabolic abdominal or pelvic visceral mass."
"There was physiological FDG tracer uptake noted within the myocardium, liver and spleen, bowel, kidneys, and urinary bladder."
"IMPRESSION: NO EVIDENCE OF FDG AVID DISEASE."
I take this to mean that there is an absence of tumor or cancer related to my MGUS, and incidentally, of any other type.
There remains, of course, for me to submit to a bone marrow biopsy to assess the extent of abnormal plasma cells responsible for the presence of my M-proteins – a painful procedure I wish to avoid as long as possible.
Protein in urine: 320 mg/24 hr, which translated to 32 mg/dL (since total volume of urine: 1000 mL).
This number contrasts with 80.1 mg/dL kappa free light chain level in the blood, reported previously.
"Urine Immunofixation Pattern Interpretation: Two free kappa paraprotein peaks detected."
In reporting this result on the phone, my onc gave me the impression that this was not surprising given the appearance of a fair amount of kappa free light chains in the blood.
The PET/CT scans strengthen my view that the "B" in the "CRAB" criteria can be disregarded, in accord with my earlier view based on my being asymptomatic. I quote the specific findings in the radiology report:
"There is no evidence of hypermetabolic osseous lesions within the visualized axial and appendicular skeleton. The Coregistered CT scan did not reveal any osteolytic destructive lesions."
"There was no focal pulmonary parenchymal hypermetabolic abnormality. The liver ... without focal intrinsic abnormality. ... no enlarged or hypermetabolic lymph nodes ... no hypermetabolic abdominal or pelvic visceral mass."
"There was physiological FDG tracer uptake noted within the myocardium, liver and spleen, bowel, kidneys, and urinary bladder."
"IMPRESSION: NO EVIDENCE OF FDG AVID DISEASE."
I take this to mean that there is an absence of tumor or cancer related to my MGUS, and incidentally, of any other type.
There remains, of course, for me to submit to a bone marrow biopsy to assess the extent of abnormal plasma cells responsible for the presence of my M-proteins – a painful procedure I wish to avoid as long as possible.
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Mort - Name: Morton Golub
- When were you/they diagnosed?: MGUS - July 2008
- Age at diagnosis: 83
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