Hello everyone,
After my autologous stem cell failed following 14 months of complete response, my oncologist put me on two different drug combos. The last one, which I had been on for over a year, dramatically lowered my kappa free light chains, as revealed by month blood tests. (I was diagnosed with kappa light chain myeloma in 2015.)
However, over the past four months, the free light chains began creeping up slowly, and he ordered a bone marrow biopsy to prepare for a change in treatment.
The biopsy showed that 98% of my marrow had been replaced by myeloma!
I asked him how a free light chain reading from the blood test of 38 mg/dL could be consistent with such a reading of 98% in the marrow.
He said my myeloma had become nonsecretory.
I then referred to a biopsy done after I relapsed 14 months following the transplant. It showed a new clone with many additions and deletions in addition to my original strain of myeloma.
So I asked my doctor if this new clone was nonsecretory and had become dominant, unaffected by my current treatment.
He said that would be a research question. To be sure, he is right about that. But my most recent biopsy only shows the original myeloma strain and this same new one.
Here's what I don't understand. Because all myeloma cells belonging to a given clone are identical (by definition), how can it be that most of them have switched from secreting light chains to not secreting anyting at all–– that is, from being light chain myeloma cells to being nonsecretory myeloma cells?
I would appreciate anyone’s thoughts.
Many thanks!
Forums
4 posts
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MrPotatohead - Name: MrPotatohead
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: March, 2015
- Age at diagnosis: 65
Re: Kappa light chain myeloma clone now nonsecretory?
Hi MrPotatohead,
You've certainly got an interesting situation!
I think that, before we can really answer the question you've asked, we need to know more about why you feel that there was no change in the two strains of myeloma you have from when you had light chain myeloma to when you had nonsecretory myeloma.
How was it determined that you have two clones, and what were the identifying characteristics of each of the two clones?
You've certainly got an interesting situation!
I think that, before we can really answer the question you've asked, we need to know more about why you feel that there was no change in the two strains of myeloma you have from when you had light chain myeloma to when you had nonsecretory myeloma.
How was it determined that you have two clones, and what were the identifying characteristics of each of the two clones?
Re: Kappa light chain myeloma clone now nonsecretory?
Hello, Cheryl G,
Thank you so much for your response!
Here’s the summary from my first bone marrow biopsy, done in March, 2015, when I was first diagnosed with kappa light chain multiple myeloma:
“The bone marrow biopsy showed hypercellular marrow at 90% with increase in plasmacytosis at 90% of total cellularity, focal mild reticulin fibrosis at MF-1 with absence of iron stain. Flow cytometry found kappa restricted plasma cells. Cytogenetics at that time found a normal male karyotype but his FISH analysis showed t(11;14) with monosomy 13”
Another bone marrow biopsy before my autologous transplant in 2017 was virtually identical to the above in results. One done after the transplant was as well, except that my percentage of myeloma cells was very low, and showed a complete response.
Then, after the serum free light chain assay, through which my myeloma was being tracked, showed a marked increase in my kappa free light chains, another bone marrow biopsy was done, in May, 2019:
“The bone marrow biopsy showed normocellular marrow with involvement by a kappa-restricted plasma cell neoplasm accounting for approximately 20 to 30% of the marrow elements. 4% myeloma cells were shown by flow cytometry. A corresponding FISH panel showed 13q deletion, and gains of chromosome 5, 9, and 15. Cytogenetic analysis showed an abnormal male karyotype, five cells showed a near tetraploid karyotype with multiple chromosome abnormalities including gains of chromosome 3 and two markers, a deletion of 3p, additional material attached to the long arm of chromosome 13 and losses of chromosome 8, 10, 13, 14 and 16.’
This result was markedly different from previous ones, and my questions to my oncologist, as well as my own Internet research, led me to the concept of “clonal evolution”, that in this case may have been triggered by the transplant itself, and that what we were seeing could be the result of that.
My treatment regimen was changed, and, still being tracked by the serum free light chain assay, my free kappa chains began to improve and stabilized at a low level, remaining that way until summer, 2019, with minor fluctuations upward and downward.
However, as an upward trend seemed to take hold in late summer of last year, another bone marrow biopsy was done in early September, 2020, and this biopsy’s cytogenetic findings were summarized as follows:
“The clonal abnormalities, observed in a previous specimen, are not observed in the cells analyzed from the current specimen. And normal karyotypes were observed in other previous specimens.”
The only deletion/translocation found was 13q, which appeared under both cytogenetics and FISH analysis.
And my marrow was found to be 98% myeloma cells under this last biopsy!
Still, my free kappa light chains, measured by the serum test, were still relatively low at just over 50 mg/dL. My oncologist’s explanation was that my myeloma had become nonsecretory.
So my thought was that perhaps the wildly abnormal features shown in the May, 2019 biopsy report, characterized a separate “strain” of the myeloma which is nonsecretory, rather than the strain that continues to secrete free light chains, and it was/is this new strain (if it is new) that is responsible for the rapid increase in myeloma cells, because myeloma cells, being monoclonal, cannot differ in their secretory behavior.
Is that a reasonable conclusion?
Since I posted on this, another explanation occurred to me: Perhaps, my myeloma has now begun to secrete kappa light chains much more slowly than earlier, and the blood levels of free light chains no longer correlate well with the number of myeloma cells actually detected in biopsy.
Thank you again, Cheryl.
Thank you so much for your response!
Here’s the summary from my first bone marrow biopsy, done in March, 2015, when I was first diagnosed with kappa light chain multiple myeloma:
“The bone marrow biopsy showed hypercellular marrow at 90% with increase in plasmacytosis at 90% of total cellularity, focal mild reticulin fibrosis at MF-1 with absence of iron stain. Flow cytometry found kappa restricted plasma cells. Cytogenetics at that time found a normal male karyotype but his FISH analysis showed t(11;14) with monosomy 13”
Another bone marrow biopsy before my autologous transplant in 2017 was virtually identical to the above in results. One done after the transplant was as well, except that my percentage of myeloma cells was very low, and showed a complete response.
Then, after the serum free light chain assay, through which my myeloma was being tracked, showed a marked increase in my kappa free light chains, another bone marrow biopsy was done, in May, 2019:
“The bone marrow biopsy showed normocellular marrow with involvement by a kappa-restricted plasma cell neoplasm accounting for approximately 20 to 30% of the marrow elements. 4% myeloma cells were shown by flow cytometry. A corresponding FISH panel showed 13q deletion, and gains of chromosome 5, 9, and 15. Cytogenetic analysis showed an abnormal male karyotype, five cells showed a near tetraploid karyotype with multiple chromosome abnormalities including gains of chromosome 3 and two markers, a deletion of 3p, additional material attached to the long arm of chromosome 13 and losses of chromosome 8, 10, 13, 14 and 16.’
This result was markedly different from previous ones, and my questions to my oncologist, as well as my own Internet research, led me to the concept of “clonal evolution”, that in this case may have been triggered by the transplant itself, and that what we were seeing could be the result of that.
My treatment regimen was changed, and, still being tracked by the serum free light chain assay, my free kappa chains began to improve and stabilized at a low level, remaining that way until summer, 2019, with minor fluctuations upward and downward.
However, as an upward trend seemed to take hold in late summer of last year, another bone marrow biopsy was done in early September, 2020, and this biopsy’s cytogenetic findings were summarized as follows:
“The clonal abnormalities, observed in a previous specimen, are not observed in the cells analyzed from the current specimen. And normal karyotypes were observed in other previous specimens.”
The only deletion/translocation found was 13q, which appeared under both cytogenetics and FISH analysis.
And my marrow was found to be 98% myeloma cells under this last biopsy!
Still, my free kappa light chains, measured by the serum test, were still relatively low at just over 50 mg/dL. My oncologist’s explanation was that my myeloma had become nonsecretory.
So my thought was that perhaps the wildly abnormal features shown in the May, 2019 biopsy report, characterized a separate “strain” of the myeloma which is nonsecretory, rather than the strain that continues to secrete free light chains, and it was/is this new strain (if it is new) that is responsible for the rapid increase in myeloma cells, because myeloma cells, being monoclonal, cannot differ in their secretory behavior.
Is that a reasonable conclusion?
Since I posted on this, another explanation occurred to me: Perhaps, my myeloma has now begun to secrete kappa light chains much more slowly than earlier, and the blood levels of free light chains no longer correlate well with the number of myeloma cells actually detected in biopsy.
Thank you again, Cheryl.
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MrPotatohead - Name: MrPotatohead
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: March, 2015
- Age at diagnosis: 65
Re: Kappa light chain myeloma clone now nonsecretory?
Hello Mr. Potatohead,
Thanks for sharing about your biopsy results. I hope that you can get this turned around soon.
Best regards,
Nancy
Thanks for sharing about your biopsy results. I hope that you can get this turned around soon.
Best regards,
Nancy
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Nancy Shamanna - Name: Nancy Shamanna
- Who do you know with myeloma?: Self and others too
- When were you/they diagnosed?: July 2009
4 posts
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