[Mildred]

Kappa / lambda ratio & myeloma defining events

by Mildred on Tue Aug 11, 2015 6:31 pm

With a kappa / lambda ratio of 2.31, how is this calculated in regards to the new criteria of a ratio of over 100 ratio being a defining number? Can some one tell me what 2.31 equals in these equations?

Thanks

[Multibilly]

Re: Kappa / lambda ratio & myeloma defining events

by Multibilly on Tue Aug 11, 2015 7:43 pm

Mildred,

I am not quite sure I understand your question, but I will try to answer it.

A normal range for the serum (blood) free light chain (FLC) ratio is 0.26 - 1.65. Based on your earlier posts, your husband is smoldering. I'm assuming from this post that his latest FLC ratio is 2.31, which is just barely out of that normal range. His kappa free light chain numbers would need to increase significantly for the FLC ratio to hit 100 (which is a "myeloma defining event"), as described below.

SV Rajkumar, "New Criteria For The Diagnosis Of Multiple Myeloma And Related Disorders," The Myeloma Beacon, Oct 26, 2014

The revised IMWG criteria will allow, in addition to the classic CRAB features, the following markers as “myeloma defining events” (MDEs) ...

Serum involved / uninvolved free light chain ratio of 100 or greater, provided the absolute level of the involved free light chain is at least 100 mg/L (a patient’s “involved” free light chain – either kappa or lambda – is the one that is above the normal reference range; the uninvolved light chain is the one that typically is in, or below, the normal range)"

Most smoldering patients would love to have an FLC ratio as good as 2.31. My FLC ratio is about 17, which is also not considered to be of concern for a smoldering patient.

[Mildred]

Re: Kappa / lambda ratio & myeloma defining events

by Mildred on Tue Aug 11, 2015 11:05 pm

Dear Multibilly,

Thank you again for your help, You have been such a blessing for many of us here, and for this I thank you.

I am happy with your answer. The numbers are confusing to me and I wish I could explain my­self better, but it is confusing to me in this way. As I stated, my husband's ratio is 2.31 and, after reading that "100" was myeloma defining, I wondered is 2.31 equal to "such and such" number. As you stated, your ratio is 17, and my husband's is 2.31. What measurement or formula is used?

If I have confused you, please forgive me, and if you cannot understand my question, I com­plete­ly understand.

[Multibilly]

Re: Kappa / lambda ratio & myeloma defining events

by Multibilly on Wed Aug 12, 2015 8:28 am

Mildred,

The equation for figuring out the FLC ratio is simply to divide the involved free light chain number (in you husband's case, the kappa number) by the uninvolved free light chain number (the lambda value). That is, kappa/lambda = your free light chain ratio for kappa-type multiple myeloma. This is also the number that is reported on your lab test. It's really that simple.

Folks that have lambda-type myeloma (like me) do the opposite and just divide lambda by kappa to get their FLC ratio when trying to compare their FLC ratio to the myeloma defining event FLC ratio of 100. So, lambda-type multiple myeloma folks have to invert the ratio that is reported on their lab test results to make this comparison.

[Ron Harvot]

Re: Kappa / lambda ratio & myeloma defining events

by Ron Harvot on Wed Aug 12, 2015 1:45 pm

Mildred,

As Multibilly has indicated, the ratio has to be at least 100 but also the involved light chain (in your husband's case, kappa) also has to be at least 100 mg/L.

In a simple example: Let's assume a patient has a kappa light chain of 100 and a lambda light chain of 1. The ratio would be 100 (100/1=100).

Your husband is 2.31. You should be able to see his sFLC overall test results which will give you his kappa and lambda standalone numbers. Then you can calculate out the ratio by just dividing the kappa number by the lambda number.

It sounds like he is doing well.

Good luck

[Mildred]

Re: Kappa / lambda ratio & myeloma defining events

by Mildred on Wed Aug 12, 2015 9:34 pm

Thank you for your response. There are so many helpful people here, it is truly a blessing. I am my husband's caretaker, although he is in excellent health, other then the smoldering multiple myeloma. I am the one of the couple's "equation" who worries!

Thanks again

[vanL]

Re: Kappa / lambda ratio & myeloma defining events

by vanL on Wed Sep 02, 2015 4:02 pm

New user info and question. I come from a different background (CLL - chronic lymphocytic leukemia). My oncologist ran tests recently and added the serum free light chain and beta-2M tests to my other standard testing. These had not been run in my two years with him. I have not had a bone marrow biopsy or FISH testing, nor any treatment.

Background test info:
B-2M: 2.19.
IFE states: Monoclonal IgA lambda protein is present. Polymerization pattern is noted.

SPE test & interpretation:

M-Spike % (g/dL) = 0.33: M-Spike2 = 0.10.
Two restricted bands with monoclonal proteins present. Peaks account for 0.33 g/dL of the total 0.43 g/dL of protein in the beta-2 region and 0.10 g/dL of the total 0.31 g/dL of protein in the gamma region.

IgG = 305
IgA = 452
IgM = 6.

Free light chain results:

Kappa free light chain = 0.62 mg/dl.
Lambda free light chain = 55 mg/dl.
K/L Ratio = 0.01.

(Converting these to mg/L: K FLC = 6.2, L FLC = 550, K/L Ratio = 0.10)

Question: The IMWG criteria states that for smoldering multiple myeloma or multiple myeloma to be diagnosed, the involved light chain must be over 100 and the ratio must be over 100. My lambda is well over 100 @ 550. My ratio, using L/K vs. K/L because I am IgA lambda = 88.71. Is this considered high in the myeloma world or might it be considered normal for a CLL person with MGUS?

Thanks in advance ... I post because I have exhausted my abilities to search the internet of information on IgA & light chains associated with MGUS /multiple myeloma/ CLL, . Can't seem to find information. Any and all comments appreciated!

Best to you all.

[TerryH]

Re: Kappa / lambda ratio & myeloma defining events

by TerryH on Thu Sep 03, 2015 9:47 am

Hi vanL,

Given that you've been diagnosed with CLL, I imagine that you're seeing a hematologist-oncologist, perhaps one who specializes in CLL. What was their interpretation and explanation for the results?

I did a quick Internet search and found many discussions of free light chain testings and CLL. I just Googled "serum free light chain chronic lymphocytic leukemia". Apparently, it's not at all abnormal for free light chain results to be outside of the normal range in CLL. Kappa and lambda levels can be individually, or both, out of range, as can the ratio.

Here are a few references that should get you started in understanding the situation better:

"Monoclonal and polyclonal serum free light chains and clinical outcome in chronic lymphocytic leukemia"
http://www.ncbi.nlm.nih.gov/pubmed/21765023

"Prognostic significance of serum free light chains in chronic lymphocytic leukemia"
http://www.ncbi.nlm.nih.gov/pubmed/24288537

"Extended use of serum free light chain as a biomarker in lymphoproliferative disorders: a comprehensive review"
http://www.ncbi.nlm.nih.gov/pubmed/22586047

Personally, I think a bone marrow biopsy, probably combined with some skeletal imaging, would be a good idea at this point to understand better what precisely your diagnosis is -- i.e., if it's just CLL, or perhaps CLL combined with myeloma.

There have been cases of combined CLL and myeloma reported in the literature. Here is one study on the subject:

"Diagnostic and clinical considerations in concomitant bone marrow involvement by plasma cell myeloma and chronic lymphocytic leukemia/monoclonal B-cell lymphocytosis: a series of 15 cases and review of literature"
http://www.ncbi.nlm.nih.gov/pubmed/23544940

Note that the full text is available for all the articles I've linked to above.

Good luck!

[vanL]

Re: Kappa / lambda ratio & myeloma defining events

by vanL on Thu Sep 03, 2015 3:46 pm

TerryH,

Thanks so much for posting and for the links. I have seen two of them, but dismissed them as they more or less said the sky was blue as if it was not normally. The other two are interesting (top two) and if I understand the way they use P values, their confidence levels were very low (as was their sample sizes).

This gives me more info and I am thankful to have it, but at the same time it seems the information suggests that CLL plays a role in myeloma activity and vise versa, but the "by how much" is not explained. Perhaps not fully investigated.

Mostly what I gathered from one of the links is that sFLC elevation + abnormal sFLC ratio 'seem' to be independent predictors for worse outcomes, regardless of testing by FISH, sometimes, B-2M, etc.

If possible, could someone please explain the serum FLC ratio as I presented it and tell me which is correct? By the standard K/L ratio I am low and high lambda FLC. Inverting because I am IgA, means dividing L by K and therefore I am high ratio + high lambda FLC. Which is the correct way to view it and is 0.01 or 88 as a ratio exceptionally high or no big deal?

As a note, I have applied to the NIH for a study and hope to be in this fall for evaluation of CLL. Perhaps my MGUS and FLC information will be interesting to them.

Thanks so much for helping. Folks who I've spoken with who have CLL almost never discuss FLC, FLC ratios, MGUS, or monoclonal protein levels. My doc is not a specialist, says not to worry - but he decided to test for these new assays for some reason.

[TerryH]

Re: Kappa / lambda ratio & myeloma defining events

by TerryH on Fri Sep 04, 2015 3:53 pm

Hi van,

If it had been established that overproduction of monoclonal plasma cells was the source of your free light chain levels and imbalance, then the ratio you would focus on is the one calculated by dividing the free light chain level that is above normal by the free light chain level that is normal or low.

That calculation yields the ratio of the "involved" free light chain to the "uninvolved" free light chain.

The thing that has to be kept in mind when reviewing the diagnostic criteria for a myeloma diagnosis, however, is that they only apply when doctors are sure that a plasma cell disorder is what is causing the symptoms.

That is why a bone marrow biopsy is an important part of the diagnostic workup. It allows doctors to tell if there are really monoclonal plasma cells in the marrow that are the source of the signs and symptoms.

The biopsies aren't perfect, because myeloma can be a "patchy" disease, with spots in the bones where it is heavily concentrated, and others where it hardly can be found. So a biopsy doesn't always settle the issue.

But going back to your question, if you were someone who has had MGUS or smoldering myeloma, and no other disease that might cause out-of-range free light chain results, then, yes, the ratio you would be focusing on in your case is the lambda-to-kappa ratio (88.7), since it would be the "involved" / "uninvolved" free light chain ratio.

I think everyone here would recommend that you see a hematologist-oncologist at a major research center to help you figure out what exactly is the correct diagnosis in your case. A specialist would have the necessary experience, and easy access to knowledgeable colleagues, to help figure out what the correct diagnosis is and what steps to take next.

Hope this helps a bit more. Good luck!