There has been quite a bit of discussion recently about secondary MGUS. There was an article on the subject posted on the Beacon recently which discussed secondary MGUS post-transplant.
"Different M-Spike After Stem Cell Transplantation Linked To Improved Survival (ASH 2012)," The Myeloma Beacon, January 16, 2013.
There also have been articles that recognize that secondary MGUS can appear pre-transplant, especially in persons who are treated with novel agents.
C Fernández de Larrea et al., "Emergence Of Oligoclonal Bands In Patients With Multiple Myeloma In Complete Remission After Induction Chemotherapy: Association With The Use Of Novel Agents," Haematologica, January 2011,96:171-173.
In my case, as detailed in the results set forth below, at original diagnosis my M-spike was identified as IgG lambda. But after several rounds of VRD, an IgG kappa M-spike appeared. and the lambda disappeared.
So the question is: What does this all mean?
Have I had a good immune response, such that the involved light chain has disappeared and the M-spike remaining is benign?
Or did I have have biclonal disease from the start and the kappa is progressing post-transplant?
Diagnosis July 3, 2013:
Hemoglobin 6.3 and several active lytic lesions; creatinine 1.43 mg/dl; calcium 9.0 mg/dL
Treatment:
Commenced 6 cycles of VRD [Velcade, Revlimid, dexamethasone] July 13, 2013;
Hemoglobin, creatinine, and calcium all normalized
Autologous stem cell transplant on January 28, 2014
Began Revlimid 10 mg maintenance March 27, 2014
Hemoglobin in the 10.5-12.6 range; creatinine and calcium mormal.
Bone Marrow Biopsies & FISH:
BMB in July 2013 showed 66% plasma cells. Follow-up biopsies September 2013 and post-transplant February 2014 showed no plasma cells.
No FISH results since initial BMB was a dry tap and subsequent BMB's yielded no plasma cells.
M-Spike Results:
2014-08-13 400 mg/dL IgG kappa
2014-07-16 300 mg/dL IgG kappa
2014-06-18 100 mg/dL IgG kappa
2014-05-21 100 mg/dL IgG kappa
2014-04-23 100 mg/dL IgG kappa
2014-03-27 100 mg/dL IgG kappa
2014-02-25 100 mg/dL IgG kappa
2014-01-28 100 mg/dL IgG kappa
2013-12-20 100 mg/dL *
2013-10-16 200 mg/dL IgG kappa 100 mg/dL IgG lambda
2013-09-09 500 mg/dL IgG lambda **
2013-07-03 5900 mg/dL IgG lambda
* No report, but report from 2014-01-28 indicates unchanged from 2103-12-20
** Notation on report: Mild irregularity in the anodal aspect of gamma, that types as IgG kappa ... too small to quantitate ... may represent restricted immune response.
Serum Lambda Free Light Chains:
2013-09-09 to present: Between 2.40 mg/dL and 0.82 mg/dL
2013-07-03 16.60 mg/dL
2013-06-30 25.45 mg/dL
Serum Kappa Free Light Chains:
2014-08-13 2.25 mg/dL
2014-07-16 2.73 mg/dL
2014-06-18 2.70 mg/dL
2014-05-21 2.87 mg/dL
2014-04-23 2.67 mg/dL
2013-09-09 to 2014-03-27 Between 0.53 mg/dL and 1.45 mg/dL
2013-06-30 0.50 mg/dL
2013-07-03 0.07 mg/dL
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Re: Secondary MGUS pre- and post-transplant?
I thought that I would add this additional reference that discusses oligoclonal banding in patients treated with a form of novel therapy but who did not receive a transplant.
T Mark et al, "Atypical serum immunofixation patterns frequently emerge in immunomodulatory therapy and are associated with a high degree of response in multiple myeloma," British Journal of Haematology, Volume 143, Issue 5, pages 654–660, December 2008.
T Mark et al, "Atypical serum immunofixation patterns frequently emerge in immunomodulatory therapy and are associated with a high degree of response in multiple myeloma," British Journal of Haematology, Volume 143, Issue 5, pages 654–660, December 2008.
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goldmine848 - Name: Andrew
- When were you/they diagnosed?: June 2013
- Age at diagnosis: 60
Re: Secondary MGUS pre- and post-transplant?
Hi Andrew,
As the IgG kappa M-protein emerged during the course of initial therapy with RVD, and as your pre-transplant bone marrow biopsy was devoid of clonal plasma cells, I suspect the presence of the low-concentration IgG kappa M-protein is related to an as-yet poorly understood immune response to effective therapy as described by Drs Mark, Niezvizky, and colleagues in the article you mention in your most recent posting in this thread.
Another explanation, as you allude to, involves the presence of two plasma cell clones at the time of your original diagnosis (a dominant IgG lambda cone, and a minor IgG kappa clone). Following this line of thought, the IgG lambda clone responded robustly to the therapy administered, while the minor IgG kappa clone did not and remains present at a level low enough that it wasn't detected on your pre-transplant bone marrow biopsy.
It may be that in the future more routine use of highly sensitive molecular techniques like PCR will allow us to understand these matters more fully, and provide more than speculative answers to important questions like you raise.
At present, it appears you are in an outstanding response overall, which is very encouraging.
Jacob Laubach
As the IgG kappa M-protein emerged during the course of initial therapy with RVD, and as your pre-transplant bone marrow biopsy was devoid of clonal plasma cells, I suspect the presence of the low-concentration IgG kappa M-protein is related to an as-yet poorly understood immune response to effective therapy as described by Drs Mark, Niezvizky, and colleagues in the article you mention in your most recent posting in this thread.
Another explanation, as you allude to, involves the presence of two plasma cell clones at the time of your original diagnosis (a dominant IgG lambda cone, and a minor IgG kappa clone). Following this line of thought, the IgG lambda clone responded robustly to the therapy administered, while the minor IgG kappa clone did not and remains present at a level low enough that it wasn't detected on your pre-transplant bone marrow biopsy.
It may be that in the future more routine use of highly sensitive molecular techniques like PCR will allow us to understand these matters more fully, and provide more than speculative answers to important questions like you raise.
At present, it appears you are in an outstanding response overall, which is very encouraging.
Jacob Laubach
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Dr. Jacob Laubach - Name: Jacob Laubach, M.D., M.P.P.
Beacon Medical Advisor
Re: Secondary MGUS pre- and post-transplant?
Thank you Dr. Laubach.
As to the second possibility: Is there any cause for concern given that the kappa M-spike is rising post-transplant?
As to the second possibility: Is there any cause for concern given that the kappa M-spike is rising post-transplant?
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goldmine848 - Name: Andrew
- When were you/they diagnosed?: June 2013
- Age at diagnosis: 60
Re: Secondary MGUS pre- and post-transplant?
Goldmine,
Just came across the recent study below which offers a differing opinion from the "Different M-Spike After Stem Cell Transplantation Linked To Improved Survival" article at the Beacon with regard to oligoclonal banding and its implications.
M Fujisawa et al, "Oligoclonal bands in patients with multiple myeloma: its emergence per se could not be translated to improved survival," Cancer Sci. 2014 Sep 2 (Epub before print)
Abstract:
The emergence of oligoclonal bands (OB) has been reported in patients with multiple myeloma (multiple myeloma) after stem cell transplantation (SCT) or successful chemotherapy. However, their clinical relevance remains unclear.
We reviewed the clinical records of multiple myeloma patients from January 2006 to May 2014. Treatment response was evaluated by International Working Group (IMWG) criteria. Serum immunofixation tests were performed at least every three months if the patient achieved more than very good partial response (VGPR). Free light chain (FLC) and minimal residual disease measurement by multicolor flow cytometry (MFC) were performed to evaluate the response to treatment.
Among the 163 patients included in the study, 40 developed OB. Detection rates of OB in patients with complete response (CR), VGPR, and partial response (PR) or less were 51.8%, 36.3%, and 0%, respectively. Patients with OB showed better progression-free survival (PFS) and overall survival (OS) rates than those without OB (P=0.028, P<0.001, respectively).
However, if the patients were limited to ≥VGPR or CR, development of OB did not affect PFS (P=0.621, P=0.646, respectively) or OS (P=0.189, P=0.766, respectively). OB was observed in 60% of patients after SCT, and in 36.6% of patients with more than VGPR without SCT (P<0.001). Patients with OB tended to have less minimal residual disease than those without OB (P=0.054) and its presence may affect the stringent CR criteria.
In conclusion, the emergence of OB was seen exclusively in patients with favorable responses, but its emergence per se could not be translated to improved survival
Just came across the recent study below which offers a differing opinion from the "Different M-Spike After Stem Cell Transplantation Linked To Improved Survival" article at the Beacon with regard to oligoclonal banding and its implications.
M Fujisawa et al, "Oligoclonal bands in patients with multiple myeloma: its emergence per se could not be translated to improved survival," Cancer Sci. 2014 Sep 2 (Epub before print)
Abstract:
The emergence of oligoclonal bands (OB) has been reported in patients with multiple myeloma (multiple myeloma) after stem cell transplantation (SCT) or successful chemotherapy. However, their clinical relevance remains unclear.
We reviewed the clinical records of multiple myeloma patients from January 2006 to May 2014. Treatment response was evaluated by International Working Group (IMWG) criteria. Serum immunofixation tests were performed at least every three months if the patient achieved more than very good partial response (VGPR). Free light chain (FLC) and minimal residual disease measurement by multicolor flow cytometry (MFC) were performed to evaluate the response to treatment.
Among the 163 patients included in the study, 40 developed OB. Detection rates of OB in patients with complete response (CR), VGPR, and partial response (PR) or less were 51.8%, 36.3%, and 0%, respectively. Patients with OB showed better progression-free survival (PFS) and overall survival (OS) rates than those without OB (P=0.028, P<0.001, respectively).
However, if the patients were limited to ≥VGPR or CR, development of OB did not affect PFS (P=0.621, P=0.646, respectively) or OS (P=0.189, P=0.766, respectively). OB was observed in 60% of patients after SCT, and in 36.6% of patients with more than VGPR without SCT (P<0.001). Patients with OB tended to have less minimal residual disease than those without OB (P=0.054) and its presence may affect the stringent CR criteria.
In conclusion, the emergence of OB was seen exclusively in patients with favorable responses, but its emergence per se could not be translated to improved survival
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Secondary MGUS pre- and post-transplant?
Thanks for the information MB.
It seems as if in large measure OB is confirmatory of the importance of achieving a deep response.
What is still unclear to me is how to view and assess the M-Spike which is the result of OB. It is said to be benign if it is a different clone from the one present at diagnosis. But does that mean you completely ignore it and can be in complete remission if that is only source of the M-Spike and you fulfill all of the other criteria of CR?
And how do you really know that it is benign rather than the emergence of another active myeloma clone which was not detected at diagnosis, especially given the weaknesses of assessing the presence of myeloma cells using bone marrow biopsy and similar testing techniques, which can miss plasma cells given the patchy distribution of the cells in the marrow?
It seems as if in large measure OB is confirmatory of the importance of achieving a deep response.
What is still unclear to me is how to view and assess the M-Spike which is the result of OB. It is said to be benign if it is a different clone from the one present at diagnosis. But does that mean you completely ignore it and can be in complete remission if that is only source of the M-Spike and you fulfill all of the other criteria of CR?
And how do you really know that it is benign rather than the emergence of another active myeloma clone which was not detected at diagnosis, especially given the weaknesses of assessing the presence of myeloma cells using bone marrow biopsy and similar testing techniques, which can miss plasma cells given the patchy distribution of the cells in the marrow?
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goldmine848 - Name: Andrew
- When were you/they diagnosed?: June 2013
- Age at diagnosis: 60
6 posts
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