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Can you have an M-spike but a normal FLC ratio?

by DanaH on Mon Jan 27, 2014 6:18 pm

If someone is willing to explain how the multiple myeloma plasma cells secrete these proteins during active disease, I would greatly appreciate it.

I realize one can have light chain only multiple myeloma where one has excess free light chains only expressed by their plasma cells resulting in an abnormal FLC ratio only, and they do not have a measurable m-spike.

But can one have a heavy chain only M-protein myeloma (m-spike with a normal FLC ratio)? Or do M-spikes always go hand in hand with abnormal levels of excess Free light chains ?

Thanks much !

All the best,
Dana H

DanaH
Who do you know with myeloma?: Myself, SMM as of 1/2012
When were you/they diagnosed?: 1/2012
Age at diagnosis: 54

Re: Can you have an M-spike but a normal FLC ratio?

by Multibilly on Mon Jan 27, 2014 6:43 pm

How are the FLCs being measured Dana? If it isn't being done with a Freelite Chain Assay, I believe that the other measurement techniques are not that accurate when you have lower FLC levels.

What are the FLC values, FLC ratio and accompanying M-Spike levels?

Also remember that FLCs are expressed in ranges. So, a given FLC could be elevated, but still fall within the "acceptable" range, esp if the M-Spike isn't that large. The elevated FLC's counterpart could also be slightly depressed, thereby bringing the ratio back into the normal range, even if one of the FLCs is elevated. On the other hand with M-Spikes, you are talking about a specific number (anything above zero) as being abnormal, not a range of values.

Multibilly
Name: Multibilly
Who do you know with myeloma?: Me
When were you/they diagnosed?: Smoldering, Nov, 2012

Re: Can you have an M-spike but a normal FLC ratio?

by Dan D on Tue Jan 28, 2014 12:44 am

While an M spike typically presents with an abnormal free light chain ratio (or high levels of one of the light chains) - I think more than 95% of the time, it can also occur with normal FLCs. A normal FLC profile is regarded as a good indicator, because it suggests a less complicated set of genetic mutations underlying the disease. But do confirm the profile with the sensitive freelight assay.

Dan D

Re: Can you have an M-spike but a normal FLC ratio?

by Multibilly on Tue Jan 28, 2014 7:55 am

Hi Dan,

Why would a normal FLC profile suggest a less complicated set of genetic mutations? I have clean cytogenetics, but my FLC ratio via Freelite assay is 0.04 (Lambda = 21, Kappa = 0.78 mg/dL) with an M-Spike of 2.16 g/dL.

Also, when you say "less complicated set of mutations", are you saying that there are possibly less different subclonal populations of cells as opposed to less deleterious mutations like the ones that would show up in one's FISH (e.g. t(4;14), del(17p13), etc) ?

Multibilly
Name: Multibilly
Who do you know with myeloma?: Me
When were you/they diagnosed?: Smoldering, Nov, 2012

Re: Can you have an M-spike but a normal FLC ratio?

by Nancy Shamanna on Tue Jan 28, 2014 9:58 am

I have had the same sort of lab tests. Once, I had an slightly elevated FLC ratio, with no 'M' spike, and more recently a low level of 2 'M' spikes but with no abnormal FLC results. Perhaps because the tests are showing very low levels of myeloma, which are not high enough to warrant treatment yet, there is some variation in the results. These are very sensitive types of lab tests. What this tells me is that I have to be very vigilant with my health, since obviously the myeloma is still in my system, but at a much much lower level than it was at the time of my diagnosis. Thoughts on this anyone?

Nancy Shamanna
Name: Nancy Shamanna
Who do you know with myeloma?: Self and others too
When were you/they diagnosed?: July 2009

Re: Can you have an M-spike but a normal FLC ratio?

by Ron Harvot on Tue Jan 28, 2014 1:21 pm

I have IgG Kappa Light Chain multiple myeloma and at the time of diagnosis did not have a measurable M spike. My Kappa level at that time was about 95 and my Lambda was below normal with a ratio of over 42. That was 5 years ago.

After initial RVD treatment the numbers came back into the normal range in the sFLC Assay. I am on a maintenance dosage of VD once every 2 weeks. My Kappa numbers recently have gone below normal with the Lambda levels in the low normal area but climbing slightly. The ratio which always was above 1.0 is still normal but, due to the fall in the Kappa light chains, is now below 0.4. For the first time I have shown an M spike, but it is low at 0.2, and is a IgG Kappa.

This is odd as I never had one before, and is even more odd since the sFLC show a drop below normal in the Kappa. My total IgG in the immunuglobulin test has been about the same, maybe just a slight drop over the last 2 tests.

My oncologist is more focused on the sFLC test than the sPEP test.

I don't have explanation for this.

Ron

Ron Harvot
Name: Ron Harvot
Who do you know with myeloma?: Myself
When were you/they diagnosed?: Feb 2009
Age at diagnosis: 56

Re: Can you have an M-spike but a normal FLC ratio?

by DanaH on Tue Jan 28, 2014 1:50 pm

Thanks everyone for the responses, following them all.

DanaH
Who do you know with myeloma?: Myself, SMM as of 1/2012
When were you/they diagnosed?: 1/2012
Age at diagnosis: 54

Re: Can you have an M-spike but a normal FLC ratio?

by DanaH on Tue Jan 28, 2014 2:05 pm

Re the comments re clonal/genetic mutations. Don't all multiple myeloma cells have some kind of chromosomal abnormality? Isn't that why the cells are deemed abnormal? Can one have "normal" FISH and have multiple myeloma ?

My 3 year old FISH did not show any abnormalities (at least for the abnormalities they specifically tested for in the multiple myeloma panel this particular lab performed), but my cells are expressing CCND1/Cyclin D-1. So in theory, the t(11;14) creates that dysregulation expression....but the t(11;14) did not show up on my FISH - could it be something as simple as not having a "good" sample to test ??

I have been reading that GEP may be more sensitive (not sure if that is the correct term) than FISH and may detect abnormalities that FISH might miss since FISH is specific probe based testing. If the specific probe is not "ordered," the abnormality would not be detected. Am I off base with this info?

(I know I should link to a valid source when I write these things, but working from my tablet again).

My learning curve seems to take a nosedive many times over.

DanaH
Who do you know with myeloma?: Myself, SMM as of 1/2012
When were you/they diagnosed?: 1/2012
Age at diagnosis: 54

Re: Can you have an M-spike but a normal FLC ratio?

by Dianem on Tue Jan 28, 2014 3:05 pm

Hi Dana and others - I've been wanting to ask the same question you presented; 'Don't all multiple myeloma cells have some kind of chromosomal abnormality?' I know of another woman with the same Ig MGUS as myself, but her FISH results were normal whereas I have a mutant clone of trisomic 7. We also have similar M spikes, but the Ig level varies - I assumed the Ig level would correlate with the M spike, but apparently it does not.

I realize an M spike is abnormal, but question if having a mutant clone identified by FISH places one in a higher risk for progression than someone with an M spike with normal FISH results.

Thanks, Diane

Dianem

Re: Can you have an M-spike but a normal FLC ratio?

by Multibilly on Tue Jan 28, 2014 4:39 pm

The thing you need to remember with various measurements like flow cytometry and FISH is that they utilize a limited number of "probes" to find specific mutations that are deemed to be of interest for a specific disease. It's not like these measurement techniques catch all the mutations that exist in your chromosomes. They are just set up to look for a very specific number of mutations that the medical industry has deemed the most important mutations to look for in a given disease.

The labs where your tests are run buy specific probe kits for specific diseases for the various testing machines that they do the genetic analysis on. There is one "kit" that they buy for myeloma and another kit for lymphoma, etc.

Multibilly
Name: Multibilly
Who do you know with myeloma?: Me
When were you/they diagnosed?: Smoldering, Nov, 2012

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