FLC Ratio

[Andy Friday]

Hello everyone I am new to amyloid problems and have just had my first visit to the Royal Free. I have amyloid deposits and the next stage will be an appointment with a Haematologist. I have been impressed with this site and how well informed everyone appears to be.
I have a question which I hope someone can answer, on my blood results the FLC Ratio appears to be Kapppa / Lambda? The figures given for the normal range appears to be calculated differently. Can anyone explain please how this should be calculated.
Normal Kappa is 3.3 - 19.4 mg/l Lambda 5.7- 26.3 giving a ratio or 0.26-1.65
I am planning to track these readings and need to make sure my understanding is correct. Thanks in anticipation.

Andy

[Miriam Vered]

Hi Andy,
Welcome to the forum.

When AL amyloidosis is first diagnosed, the free light chain ratio is checked:

• If the abnormal plasma cells are secreting kappa chains, the kappa/ lambda ratio is checked.
• If the abnormal plasma cells are secreting lambda chains, the lambda/kappa ratio is checked.

The normal kappa/lambda ratio is 0.26-1.65 but when monthly FLC tests are used to follow the patient’s response to chemotherapy, the dFLC (difference between involved and uninvolved FLCs) method is now often used. For this test, the concentration of the normal light chain type is subtracted from the concentration of the abnormal light chain type:

• If a patient with AL amyloidosis has amyloid due to abnormal production of kappa chains, dFLC concentration is kappa chain concentration minus lambda chain concentration.
• If a patient with AL amyloidosis has amyloid due to abnormal production of lambda chains, dFLC concentration is lambda chain concentration minus kappa chain concentration.

The best method, at least the most accessible/obvious method in any given patient does depend on many things including the renal function and difference between kappa and lambda values.

Some more information on understanding FLC results is available here.

I discussed this with Professor Hawkins and he also recommends that you (and other patients seeking better understanding of their FLC results) should discuss your particular FLC results with your haematologist.

I hope this helps to clarify things

[Andy Friday]

Hello Miriam

Thanks for your reply, unfortunately I am none the wiser.  I do appreciate the absolute need to be guided by Haematologist and other professionals in this very specific field when discussing and or understanding these readings
My query stems from my first Cumulative Blood results sent to me by your good selves which gives my Kappa, Lambda and FLC Ratio which is a simple calculation of Kappa divided by Lambda to equal FLC Ratio. Above my results on this form appear to be normal readings for Kappa, Lambda and associated FLC Ratio presented in a min and max range. It is the method used to calculate this FLC Ratio that I do not understand. If you look on the form you use this information is between the two bold lines together with column headings.
I am keen to understand as much as I can as that helps me to formulate questions when discussing further treatments that may be required.

Andy

[Miriam Vered]

The upper and lower limits of the normal kappa/lambda ratio were calculated on the basis of population studies. I believe they correspond to the 95th centile limits.


Does that help?

[Andy Friday]

Hello Miriam

Not really but then I'm an Engineer not a Doctor, thanks for trying.

Andy

[Miriam Vered]

Hi Andy,
I'm sorry that my answers aren't giving you the information you want. I suggest that you try phoning one of the clinical research nurses and discussing it. It may be easier to explain exactly what you want to understand in a real-time conversation. Try calling Darren Foard at +44 (0)20 7433 2814.
The phone numbers of the other clinical research nurses are also available here.
Please let me know if that is helpful or if I can help in any other way.

[Joca]

Hi Andy,

I'm new to this game as well and FLC are confusing because the normal ranges are so large. κ can be 3.3-19.4 mg/mL and λ can be 5.7- 26.3 mg/mL with the ratio (κ/λ)  0.26 -1.65. So you could theoretically have κ  of 3.3 and λ  of 26.3 giving a ratio of 0.125. Both would be in the normal range but the ratio would be way out from the norm.  Similarly your ratio could be normal at 0.26 but your κ could be 19.4 and λ would be 74.6 - very high. It seems though that it is the change of ratio that is important. As your treatment progresses the ratio should return to the normal range if things go well, and much more quickly that other symptoms.
Say you presented with a κ of 100 mg/mL and a λ of 10mg/mL. Your ratio(κ/λ) is therefore 10. after a few months of chemotherapy your  κ may be now 10 mg/mL and the ratio is now 1. This would be an excellent response. If the ratio is still 10 then they will try something else.
I think there is a bit of a wobble with the ratio as if the λ went to 12 (randomly) but no change  in κ then you may think as the ratio is now 8.3 that things are improving but this is not the case, so the results sheet suggests only changes >20% are significant. There will also be imprecisions in the measurements, particularly in the lower range.
Some centres favour the dFLC (essentially the  κ-λ or  λ-κ), so in the example above this would be 100-10 = 90mg/mL. This should also get less during treatment.

I hope this helps. It has helped me writing it to better understand it. I also found a Youtube video by the manufacturers of the assay which I found helpful, primarily the first 16 minutes and especially 12-16 minutes.

https://www.youtube.com/watch?v=Ye9s6BRgx_Y

[Miriam Vered]

Thanks Joca for a very clear explanation.

[Mike]

My wife light chains always remain within the allowed perimeter as does the ratio,however she is now on her. Third relapse looking to start fourth chemo as her para protein is at 11 and liver and kidney functions not good could someone explain why her light chains do not help with monitoring her condition ?

[Andy Friday]

Hello Joca

Thanks for your explanation regarding FLC ratio and the suggested YouTube video. I do need to go over the information a bit more but feel more confident to discuss my issues with the haematologist.

Once again many thanks for your help.
Andy

[Miriam Vered]

My wife light chains always remain within the allowed perimeter as does the ratio,however she is now on her. Third relapse looking to start fourth chemo as her para protein is at 11 and liver and kidney functions not good could someone explain why her light chains do not help with monitoring her condition ?

Hi Mike,
About 10-15% of patients with AL amyloidosis have only minimally abnormal FLC (defined as dFLC <50mg/l; dFLC is the difference between the amyloidogenic light chain concentration and the non-amyloidogenic light chain concentration)
For these patients FLC cannot be used for accurate monitoring. A measurable M-protein (also known as paraprotein), defined as >5g/l, is useful for monitoring the haematological response to chemotherapy in this  10-15% of patients with minimally abnormal FLC. It sounds like your wife is in this group.
1-2% of patients with AL amyloidosis lack a measurable serum or urine marker to monitor response at present. Ongoing studies are evaluating a new method called high sensitivity flow cytometry that may have a role in these patients.

[Mike]

Thanks for that Miriam .

[Mike]

My wife light chains always remain within the allowed perimeter as does the ratio,however she is now on her. Third relapse looking to start fourth chemo as her para protein is at 11 and liver and kidney functions not good could someone explain why her light chains do not help with monitoring her condition ?

Hi Mike,
About 10-15% of patients with AL amyloidosis have only minimally abnormal FLC (defined as dFLC <50mg/l; dFLC is the difference between the amyloidogenic light chain concentration and the non-amyloidogenic light chain concentration)
For these patients FLC cannot be used for accurate monitoring. A measurable M-protein (also known as paraprotein), defined as >5g/l, is useful for monitoring the haematological response to chemotherapy in this  10-15% of patients with minimally abnormal FLC. It sounds like your wife is in this group.
1-2% of patients with AL amyloidosis lack a measurable serum or urine marker to monitor response at present. Ongoing studies are evaluating a new method called high sensitivity flow cytometry that may have a role in these patients.

Miriam I was wondering if any progress had been made with the new method of sensitivity flow cytometry as my wife now on her 5th different chemo having problems with liver and kidneys and consultant looking to see if any progress is being made via panbinostat/Velcade as stated beforehand Flc are in normal range M protein has dropped some .

[Miriam Vered]

Hi Mike,

This is Dr Wechalekar's answer to your question:

As long as there is a measurable paraprotein in the blood, the multiparameter flow will not add anything to the assessment of response. The main utility in development of multiparameter flow is for detecting disease in the bone marrow when all the blood markers including paraprotein are normal - so called minimal residual disease. A paraprotein is as useful as light chains when it is measurable in the blood for tracking response to treatment. At this time, flow will not impact treatment decisions.

[Mike]

That's very useful thank you