Hello,
I have posted here before in reference to my biclonal gammopathy (see, for example, this thread). I am awaiting a follow up appointment with my oncologist to discuss recent SPEP and FLC results, but thought it would be beneficial to post here as well.
When I was initially diagnosed with smoldering multiple myeloma, I was IgG kappa, with a trace of IgG lambda - in other words, biclonal gammopathy. My kappa-lambda FLC ratio was high and my kappa was trending up. Then, after a few years, lambda became dominant and my FLC ratio was low and my lambda light chain was trending up.
Interestingly enough, after about the same amount of time the "flip" occurred the first time, it occurred again. I went to DFCI in November to see about clinical trials because I suffer from immunoparesis and my kappa-lambda FLC ratio was 0.016. When they completed the blood work for the trials, it was completely different than the blood work I had completed locally just one month before.
Thinking this was a difference in the lab, or a grievous mistake on the part of one or the other, I had my local oncologist repeat the tests and the results concurred with the DFCI results! It was official, my dominant clone flipped again. I am now kappa dominant!
Since there is so much talk about various and multiple clones in multiple myeloma and that less aggressive clones can be a good thing that prevent aggressive clones from dominating, I was wondering if an obvious biclonal gammopathy is a good thing? Is it possible that these two clones will wrestle with each other and keep my myeloma from officially progressing?
Just a curious occurrence that I hope to get an opinion on. Thank you.
J
Forums
5 posts
• Page 1 of 1
-
jhorner - Name: Magpie
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: 2013
- Age at diagnosis: 49
Re: Biclonal gammopathy - is it a good thing?
Considering I never received any response to this thread, I'm free to suppose it was very confusing. In an effort to clarify, I'd like to elaborate further with some specifics on my case.
2005-2010 - SPEP showed IgG kappa clone and IgG lambda clone MGUS with IgG kappa clone dominant and a high FLC ratio. No bone marrow biopsy was ever done during this time frame.
2011 - No measurable clone - Trace IgG kappa and trace IgG lambda only.
2012-2014 - SPEP showed IgG lambda clone and trace IgG kappa clone smoldering multiple myeloma. I had a bone marrow biopsy (BMB) to confirm that lambda was dominant and the percentage of plasma cells was 10-12%. During this time, the FLC showed the lambda was ever increasing and the kappa ever decreasing to the point where I had a low / abnormal FLC ratio. This is the time I sought out a myeloma specialist at DFCI.
2015 - FLC performed in November 2014, December 2014, and February 2015 all show that the lambda has decreased significantly and the kappa has increased, implying yet another flip of the dominant clone. I recognize that the only way to confirm this is with another BMB.
Considering I am bi-clonal and the FLC is not ideal for measuring disease burden, should I request another BMB? Has anyone else ever presented like this?
Are these two different disease states and, if so, are two different clones beneficial before treatment as they have been indicated after treatment?
I hope this is clearer.
J
2005-2010 - SPEP showed IgG kappa clone and IgG lambda clone MGUS with IgG kappa clone dominant and a high FLC ratio. No bone marrow biopsy was ever done during this time frame.
2011 - No measurable clone - Trace IgG kappa and trace IgG lambda only.
2012-2014 - SPEP showed IgG lambda clone and trace IgG kappa clone smoldering multiple myeloma. I had a bone marrow biopsy (BMB) to confirm that lambda was dominant and the percentage of plasma cells was 10-12%. During this time, the FLC showed the lambda was ever increasing and the kappa ever decreasing to the point where I had a low / abnormal FLC ratio. This is the time I sought out a myeloma specialist at DFCI.
2015 - FLC performed in November 2014, December 2014, and February 2015 all show that the lambda has decreased significantly and the kappa has increased, implying yet another flip of the dominant clone. I recognize that the only way to confirm this is with another BMB.
Considering I am bi-clonal and the FLC is not ideal for measuring disease burden, should I request another BMB? Has anyone else ever presented like this?
Are these two different disease states and, if so, are two different clones beneficial before treatment as they have been indicated after treatment?
I hope this is clearer.
J
-
jhorner - Name: Magpie
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: 2013
- Age at diagnosis: 49
Re: Biclonal gammopathy - is it a good thing?
Hi jhorner,
Indeed this is rare if it is a truly clonal process, and it sounds like this has been vetted by both a local oncologist and experts at DFCI who agree that you have a biclonal gammopathy, so I suspect it is true.
However, upon my initial read of your posting, my first concern was that your two clones were representative of an "oligoclonal" process (i. e., multiple monoclonal bands), which can occur in the setting of infection or other precipitants of an activated immune system. Do you have any other medical history in this regard?
Perhaps most informative is the bone marrow – when it was done to confirm lambda was dominant, did it show almost ALL plasma cells were lambda, or a fair mix? Did the flow cytometry show abnormal plasma cells? Was it a good specimen?
Assuming you do have true biclonal gammopathy with shifting clonal dominance, I am not aware of any good data that estimates risk. As you suggest, having multiple clones after treatment is associated with a good prognosis and is thought to represent a robust recovery of the immune system after immune suppression. In your case, if it were true biclonal disease, it would not be driven by the same process, presumably.
I am sorry if I stirred up more questions rather than providing answers. The good news is that, in the year 2015, patients with asymptomatic multiple myeloma who are being followed should not get into trouble from their disease since the likelihood that we will detect clinically significant progression prior to any symptoms / organ compromise is high.
Best!
Indeed this is rare if it is a truly clonal process, and it sounds like this has been vetted by both a local oncologist and experts at DFCI who agree that you have a biclonal gammopathy, so I suspect it is true.
However, upon my initial read of your posting, my first concern was that your two clones were representative of an "oligoclonal" process (i. e., multiple monoclonal bands), which can occur in the setting of infection or other precipitants of an activated immune system. Do you have any other medical history in this regard?
Perhaps most informative is the bone marrow – when it was done to confirm lambda was dominant, did it show almost ALL plasma cells were lambda, or a fair mix? Did the flow cytometry show abnormal plasma cells? Was it a good specimen?
Assuming you do have true biclonal gammopathy with shifting clonal dominance, I am not aware of any good data that estimates risk. As you suggest, having multiple clones after treatment is associated with a good prognosis and is thought to represent a robust recovery of the immune system after immune suppression. In your case, if it were true biclonal disease, it would not be driven by the same process, presumably.
I am sorry if I stirred up more questions rather than providing answers. The good news is that, in the year 2015, patients with asymptomatic multiple myeloma who are being followed should not get into trouble from their disease since the likelihood that we will detect clinically significant progression prior to any symptoms / organ compromise is high.
Best!
-
Dr. Heather Landau - Name: Heather Landau, M.D.
Beacon Medical Advisor
Re: Biclonal gammopathy - is it a good thing?
Jhorner,
While this is an older study, I think it's still interesting to note the following in this study:
RA Kyle et al, "The clinical aspects of biclonal gammopathies. Review of 57 cases," American Journal of Medicine, Dec 1981 (abstract)
Put another way, only 2.7% (1/37) of the biclonal MGUS cohort became symptomatic after 2 years.
While this is an older study, I think it's still interesting to note the following in this study:
RA Kyle et al, "The clinical aspects of biclonal gammopathies. Review of 57 cases," American Journal of Medicine, Dec 1981 (abstract)
Between 1966 and 1979, biclonal gammopathy was recognized in 57 patients. Clinical and laboratory features differentiated three groups: biclonal gammopathy of undetermined significance, 37 cases (65 percent); multiple myeloma, nine cases (16 percent); and lymphoproliferative disease – including lymphoma, macroglobulinemia, chronic lymphocytic leukemia and unclassified lymphoproliferative disorders – 11 cases (19 percent). With biclonal gammopathy of undetermined significance, symptomatic multiple myeloma developed after two years in one patient; the others remained stable"
Put another way, only 2.7% (1/37) of the biclonal MGUS cohort became symptomatic after 2 years.
-
Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Biclonal gammopathy - is it a good thing?
Thank you, Dr. Landau and Multibilly, as I very much appreciate your responses.
In an attempt to answer some of Dr. Landau's questions, I am including the two readings from the BMB from both institutions using the same slides that indicate specimen size " 0.7 cm X 0.1 cm." I do not see any reference to the quality of the specimen, nor do I see anything on the reports that references "flow cytometry", just cytogenetic results that I did not include here. The second read at DFCI recognized both clones.
First Read
Bone Marrow Biopsy
Mildy hypercellular marrow (40%) fat. Erythroid and myeloid elements are present and in normal proportion. Megakaryocytes are present in normal number. Stainable iron is trace positive. No amyloid identified.
An immunohistochemical study revealed positive staining of plasma cells for CD138 at approximately 10-12% of cellularity with predominance of staining for lambda light chain immunoglobulins consistent with plasma cell dyscrasia.
Second Read
Bone Marrow Biopsy (S13-14431; Aug 12, 2013):
Mildly hypercellular marrow (30% fat). Approximately 20-30% of the cellularity (10-20% of intertrabecular space) is comprised of a infiltrate of plasma cells. Immunoperoxidase and in situ hybridization studies performed on paraffin sections at the referring institution and reviewed at BWH reveal cytoplasmic reactivity of the CD138 positive plasma cells for immunoglobulin lambda light chain. Scattered plasma cells exhibit cytoplasmic reactivity for immunoglobulin kappa light chain.
Of the remaining cellularity:
Erythroid elements are present in normal proportion and exhibit maturation.
Myeloid elements are present in normal proportion and exhibit maturation.
Blasts appear to comprise less than 5% of the marrow cellularity.
Megakaryocytes are present in normal numbers. Iron stain performed at the referring institution and received for review at BWH reveals that trace iron is present. Ringed sideroblasts are not seen. Congo red stain performed at the referring institution and received for review at BWH is negative for amyloid. PAS stain examined for final diagnosis of bone marrow biopsy.
Note: The findings are of a plasma cell neoplasm.
I guess I am fortunate that the trend in my FLC ratio abruptly changed, as surprising as this was. My lambda was increasing regularly and my ratio was abnormal and it is now normal range. However, at the same time, this is what concerns me, because it seems to be uncertain if my myeloma can be measured reliably this way.
Worth mentioning is that I do have immunoparesis affecting both uninvolved immunoglobulins, and it was determined or deduced that the chronic and recurring infections was likely due to the fact that I was not making any "normal" IgG due to biclonal gammopathy. The IVIG treatments work amazingly well for me, minimizing nearly all my symptoms.
In an attempt to answer some of Dr. Landau's questions, I am including the two readings from the BMB from both institutions using the same slides that indicate specimen size " 0.7 cm X 0.1 cm." I do not see any reference to the quality of the specimen, nor do I see anything on the reports that references "flow cytometry", just cytogenetic results that I did not include here. The second read at DFCI recognized both clones.
First Read
Bone Marrow Biopsy
Mildy hypercellular marrow (40%) fat. Erythroid and myeloid elements are present and in normal proportion. Megakaryocytes are present in normal number. Stainable iron is trace positive. No amyloid identified.
An immunohistochemical study revealed positive staining of plasma cells for CD138 at approximately 10-12% of cellularity with predominance of staining for lambda light chain immunoglobulins consistent with plasma cell dyscrasia.
Second Read
Bone Marrow Biopsy (S13-14431; Aug 12, 2013):
Mildly hypercellular marrow (30% fat). Approximately 20-30% of the cellularity (10-20% of intertrabecular space) is comprised of a infiltrate of plasma cells. Immunoperoxidase and in situ hybridization studies performed on paraffin sections at the referring institution and reviewed at BWH reveal cytoplasmic reactivity of the CD138 positive plasma cells for immunoglobulin lambda light chain. Scattered plasma cells exhibit cytoplasmic reactivity for immunoglobulin kappa light chain.
Of the remaining cellularity:
Erythroid elements are present in normal proportion and exhibit maturation.
Myeloid elements are present in normal proportion and exhibit maturation.
Blasts appear to comprise less than 5% of the marrow cellularity.
Megakaryocytes are present in normal numbers. Iron stain performed at the referring institution and received for review at BWH reveals that trace iron is present. Ringed sideroblasts are not seen. Congo red stain performed at the referring institution and received for review at BWH is negative for amyloid. PAS stain examined for final diagnosis of bone marrow biopsy.
Note: The findings are of a plasma cell neoplasm.
I guess I am fortunate that the trend in my FLC ratio abruptly changed, as surprising as this was. My lambda was increasing regularly and my ratio was abnormal and it is now normal range. However, at the same time, this is what concerns me, because it seems to be uncertain if my myeloma can be measured reliably this way.
Worth mentioning is that I do have immunoparesis affecting both uninvolved immunoglobulins, and it was determined or deduced that the chronic and recurring infections was likely due to the fact that I was not making any "normal" IgG due to biclonal gammopathy. The IVIG treatments work amazingly well for me, minimizing nearly all my symptoms.
-
jhorner - Name: Magpie
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: 2013
- Age at diagnosis: 49
5 posts
• Page 1 of 1