Sorry if this question has been asked, but I can't find it if so.
My wife has light chain (kappa) multiple myeloma and underwent stem cell transplant in July. In trying to evaluate her status, we find that she satisfies criteria for complete response, but not for stringent CR. Her serum kappa light chain decreased from a high of over 11000 mg/L to the most recent value of 10.2. Her free light chain ratio decreased from over 11000 to 3.52. The normal range for the ratio tops out at 1.65. Since her kappa value is in the "normal" range, the reason that the ratio is out of normal range is that her lambda values are below normal.
Here are my questions:
1) I understand why the ratio is important since it can differentiate between disease progression and some other (e.g. inflammation) problem. What I don't understand is why a *below normal* value of lambda is still indicative of the presence of the disease even though the kappa is normal.
2) Her heavy chain proteins (IgG, IgM etc) are also slightly lower than normal. What causes this and what are the consequences?
3) The other criterion for stringent CR is no clonal cells detected in the bone marrow. The marrow biopsy didn't include any plasma cells so the jury is out here. How can biopsies find clonal plasma cells when such cells are less than 5% of the cells in the marrow?
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zephyrus - Name: Lee
- Who do you know with myeloma?: wife
- When were you/they diagnosed?: Feb, 2012
- Age at diagnosis: 64
Re: Interpreting results - light chain multiple myeloma
Hello from wet, cold and dark Seattle,
1) I do not think that the below normal lamba indicates disease. If the plasma cells and bone marrow are suppressed with chemotherapy, synthesis of both light chains will fall. Low concentrations of κ, λ, or both indicate bone marrow function impairment. This has occurred because of the chemotherapy used in the transplant. The elevated ratio is an artifact.
2) It is quite common for myeloma patients to have reduced serum immunoglobulins. In general there are no consequences but there can be. This is termed "immunoparesis". Patients with low serum immunoglobulins are at increased risk for infections (pneumonia etc). Usually we do not treat the low immunoglobulin level (with monthly infusions of immunoglobulins) unless a patient has repeated bacterial infections like pneumonia, sinusitis or bronchitis.
3) Definitions of CR vary somewhat from study to study and paper to paper. Furthermore there are several different types of CR (e.g. molecular CR, immunophenotypic CR, stringent CR etc).
For a stringent CR by the International Myeloma Working Group report in 2006 the bone marrow had to be tested for myeloma cells using a technique that is more sensitive than the < 5% criteria by immunohistochemistry (where slides are stained and examined under the microscope). This more sensitive technique is called flow cytometrey and it is many times more sensitive than simply looking for myeloma cells through a microscope.
At the end of the day, though, it sounds like your wife has had an excellent response to date. Hopefully this will be long-lasting. I suspect she is now going to be treated with maintenance therapy as maintenance can give some of the longest remissions seen post transplant in myeloma.
I wish you and your wife all the best.
Ed Libby
1) I do not think that the below normal lamba indicates disease. If the plasma cells and bone marrow are suppressed with chemotherapy, synthesis of both light chains will fall. Low concentrations of κ, λ, or both indicate bone marrow function impairment. This has occurred because of the chemotherapy used in the transplant. The elevated ratio is an artifact.
2) It is quite common for myeloma patients to have reduced serum immunoglobulins. In general there are no consequences but there can be. This is termed "immunoparesis". Patients with low serum immunoglobulins are at increased risk for infections (pneumonia etc). Usually we do not treat the low immunoglobulin level (with monthly infusions of immunoglobulins) unless a patient has repeated bacterial infections like pneumonia, sinusitis or bronchitis.
3) Definitions of CR vary somewhat from study to study and paper to paper. Furthermore there are several different types of CR (e.g. molecular CR, immunophenotypic CR, stringent CR etc).
For a stringent CR by the International Myeloma Working Group report in 2006 the bone marrow had to be tested for myeloma cells using a technique that is more sensitive than the < 5% criteria by immunohistochemistry (where slides are stained and examined under the microscope). This more sensitive technique is called flow cytometrey and it is many times more sensitive than simply looking for myeloma cells through a microscope.
At the end of the day, though, it sounds like your wife has had an excellent response to date. Hopefully this will be long-lasting. I suspect she is now going to be treated with maintenance therapy as maintenance can give some of the longest remissions seen post transplant in myeloma.
I wish you and your wife all the best.
Ed Libby
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Dr. Edward Libby - Name: Edward Libby, M.D.
Beacon Medical Advisor
Re: Interpreting results - light chain multiple myeloma
Thanks for your very informative reply.
Flow cytometrey was done. Here is the main statement:
CYTOPLASMIC MYELOMA PANEL BM
_____________________________________________
SPECIMEN TYPE (BM) BM
INTERPRETATION
Specimen is: BONE MARROW LEFT
No aberrant plasma and no normal plasma cells are present.
B-Cells are polytypic.
Does this imply that the sample was deficient, since no normal plasma cells were found?
BTW, we spent 6 years in beautiful Seattle and learned to love the rain, but now live where the annual precipittion is less than 10 inches.
Flow cytometrey was done. Here is the main statement:
CYTOPLASMIC MYELOMA PANEL BM
_____________________________________________
SPECIMEN TYPE (BM) BM
INTERPRETATION
Specimen is: BONE MARROW LEFT
No aberrant plasma and no normal plasma cells are present.
B-Cells are polytypic.
Does this imply that the sample was deficient, since no normal plasma cells were found?
BTW, we spent 6 years in beautiful Seattle and learned to love the rain, but now live where the annual precipittion is less than 10 inches.
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zephyrus - Name: Lee
- Who do you know with myeloma?: wife
- When were you/they diagnosed?: Feb, 2012
- Age at diagnosis: 64
Re: Interpreting results--light chain multiple myeloma
I have light chain myeloma and am tracked by the light chain assay. All my light chains including the ratio have been normal. I also have consistently had well below normal immunoglobulin serum readings. I have been in this remissive state for over 3 years.
However, this past year I developed recurring sinus infections and one instance of severe bronchitis. Then, in early July, I came down with C-diff and viral meningitis and was hospitalized for 4 days in isolation. Since then I was put on IVIG and taken off Revlimid. My current protocol is a Velcade shot once every 2 weeks accompanied with 20 mg of dex. I get the IVIG once a month. My oncologist is going to keep me off Revlimid and see if my light chains continue to be normal. If they begin to elevate, he will start me back on 10 mg Revlimid on 21 days, 7 days off.
I recovered from the meningitis quickly and in fact participated on a three man biking team at the end of September. We rode on a 26.5 mile course for 24 hours. Started at 6 pm on Friday ending on Saturday. We did alternating laps and each doing 106 miles or 318 miles as a team. We finished that distance in a little over 20 hours and 30 minutes. It rained almost the entire time with temps in the 50s.
I was the old man on the team having just tuned 60. My teammates are both in their 30s. The old man had the fastest average time on the team with a 15.7 mph average for the 106 miles on a hilly course. Our team took first place in this team event.
I noticed that my endurance is better now that I am off the Revlimid. I hope I can continue this way.
Ron
However, this past year I developed recurring sinus infections and one instance of severe bronchitis. Then, in early July, I came down with C-diff and viral meningitis and was hospitalized for 4 days in isolation. Since then I was put on IVIG and taken off Revlimid. My current protocol is a Velcade shot once every 2 weeks accompanied with 20 mg of dex. I get the IVIG once a month. My oncologist is going to keep me off Revlimid and see if my light chains continue to be normal. If they begin to elevate, he will start me back on 10 mg Revlimid on 21 days, 7 days off.
I recovered from the meningitis quickly and in fact participated on a three man biking team at the end of September. We rode on a 26.5 mile course for 24 hours. Started at 6 pm on Friday ending on Saturday. We did alternating laps and each doing 106 miles or 318 miles as a team. We finished that distance in a little over 20 hours and 30 minutes. It rained almost the entire time with temps in the 50s.
I was the old man on the team having just tuned 60. My teammates are both in their 30s. The old man had the fastest average time on the team with a 15.7 mph average for the 106 miles on a hilly course. Our team took first place in this team event.
I noticed that my endurance is better now that I am off the Revlimid. I hope I can continue this way.
Ron
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Ron Harvot - Name: Ron Harvot
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: Feb 2009
- Age at diagnosis: 56
Re: Interpreting results--light chain multiple myeloma
I need to point out that much of what we are doing in this discussion is "splitting hairs" and really is relevant in terms of a clinical study only and not so much in the standard treatment of myeloma. The bottom line is that your wife is in a very good place in terms of her myeloma and I am hopeful will be so for a long long time.
The IMWG (International Myeloma Working Group) response criteria from 2011 state:
Patients with κ/λ FLC ratio <0.26 are defined as having monoclonal λ FLC and those with ratios >1.65 are defined as having a monoclonal κ FLC. The monoclonal light chain isotype is referred to as the ‘involved’ FLC isotype, and the opposite light chain type is the ‘uninvolved’ FLC type. The baseline level of the involved FLC should be at least ≥10 mg/l.
That is why I am saying that the abnormal ratio does not reflect the presence of cancerous plasma cells. Your wife's baseline lambda was always normal and now is below normal (probably because of bone marrow suppression from chemotherapy). Her "involved free light chain" is kappa.
There are regular updates to the IMWG criteria. In 2009 an update to the IMWG criteria states "FLC levels vary considerably with changes in renal function and do not solely represent monoclonal elevations. Thus, both the level of the involved and the uninvolved FLC isotypes (that is, the involved-uninvolved difference) are considered in assessing response."
The negative bone marrow result by immunohistochemistry and by flow cytometry + the normalization of the involved serum free light chain (kappa) points to a complete remission.
If she was in a clinical trial her free light chains would have to be interpreted by the study investigators ( and then the low lambda would be taken into consideration) and they would decide whether or not this constitutes a true "stringent CR". Also, to have a stringent CR the patient must have 2 consecutive assessments so her next free light chain levels are important as well. All of this matters only if her SPEP at diagnosis was less that 1.0 gm/dL. If the SPEP is 1.0 or greater at diagnosis then the SPEP is the test that should be used to determine response.
The IMWG (International Myeloma Working Group) response criteria from 2011 state:
Patients with κ/λ FLC ratio <0.26 are defined as having monoclonal λ FLC and those with ratios >1.65 are defined as having a monoclonal κ FLC. The monoclonal light chain isotype is referred to as the ‘involved’ FLC isotype, and the opposite light chain type is the ‘uninvolved’ FLC type. The baseline level of the involved FLC should be at least ≥10 mg/l.
That is why I am saying that the abnormal ratio does not reflect the presence of cancerous plasma cells. Your wife's baseline lambda was always normal and now is below normal (probably because of bone marrow suppression from chemotherapy). Her "involved free light chain" is kappa.
There are regular updates to the IMWG criteria. In 2009 an update to the IMWG criteria states "FLC levels vary considerably with changes in renal function and do not solely represent monoclonal elevations. Thus, both the level of the involved and the uninvolved FLC isotypes (that is, the involved-uninvolved difference) are considered in assessing response."
The negative bone marrow result by immunohistochemistry and by flow cytometry + the normalization of the involved serum free light chain (kappa) points to a complete remission.
If she was in a clinical trial her free light chains would have to be interpreted by the study investigators ( and then the low lambda would be taken into consideration) and they would decide whether or not this constitutes a true "stringent CR". Also, to have a stringent CR the patient must have 2 consecutive assessments so her next free light chain levels are important as well. All of this matters only if her SPEP at diagnosis was less that 1.0 gm/dL. If the SPEP is 1.0 or greater at diagnosis then the SPEP is the test that should be used to determine response.
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Dr. Edward Libby - Name: Edward Libby, M.D.
Beacon Medical Advisor
5 posts
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