Guidelines
2008 Published Guidelines
International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders1
A Dispenzieri, R Kyle, G Merlini, JS Miguel, H Ludwig, R Hajek, A Palumbo, S Jagannath, J Blade, S Lonial, M Dimopoulos, R Comenzo, H Einsele, B Barlogie, K Anderson, M Gertz, JL Harousseau, M Attal, P Tosi, P Sonneveld, M Boccadoro, G Morgan, P Richardson, O Sezer, MV Mateos, M Cavo, D Joshua, I Turesson, W Chen, K Shimizu, R Powles, SV Rajkumar and BGM Durie on behalf of the International Myeloma Working Group.
Leukemia (2009) 23:215-224
"Recommendations for the use of the serum FLC assay in Screening. The serum FLC assay in combination with serum PEL and serum IFE is sufficient to screen for pathological monoclonal plasmaproliferative disorders other than AL, which requires all the serum tests as well as the 24-h urine IFE. If a diagnosis of a plasma cell disorder is made, a 24-h urine for PEL and IFE is essential for all patients."
"Recommendations for the use of the serum FLC assay in prognosis*. The serum FLC assay should be measured at diagnosis for all patients with MGUS*, smoldering or active multiple myeloma, solitary plasmacytoma and AL amyloidosis."
"Recommendations for the use of the serum FLC assay in response assessment. Serial FLC ascertainment should be routinely performed in patients with AL amyloidosis and multiple myeloma patients with oligosecretory disease. It should also be done in all patients who have achieved a CR to determine whether they have attained a stringent CR."
* In the USA diagnostic use of this product is restricted to those stated in the product insert
2006 Published Guidelines
International uniform response criteria for multiple myeloma2
BGM Durie et al.
Leukemia (2006) 20: 1467-1473
| Rationale for the development of uniform response criteria |
|---|
|
Abbreviations: CR, complete response; FLC, free light chain.
aOligo- and non-secretory myeloma identifies patients without sufficient M-component in serum and/or urine to monitor response
"...present criteria allow limited assessment of response in patients with oligo-secretory or non-secretory myeloma. Response in these patients can now be assessed using the sensitive serum free light-chain (FLC) assay (Freelite, Binding Site). Incorporation of the serum FLC assay into the response criteria for myeloma allows inclusion and evaluation of these patients in clinical trials."
"Thus, normalizing of serum FLC ratio is a stricter indicator of CR and may correlate well with extended response duration (Kumar S et al.). Note that in patients with renal insufficiency, the levels of both the kappa and lambda may remain elevated, but the ratio normalizes with achievement of CR."
The International uniform response criteria has indicated using the difference in values between the tumour involved light chain and the uninvolved light chain. These criteria provide standardisation for clinical outcomes in trials.
Sections relevant to serum free light chain (FLC) measurements:
| Response | Criteria |
|---|---|
| Stringent Complete Response (sCR) | Normal serum FLC ratio |
| Measurable disease* | Abnormal serum FLC ratio and involved serum FLC > 100 mg/L |
| Partial Response* | > 50% decrease in the difference between involved and uninvolved FLC levels |
| Progressive disease* | Increase > 25% from baseline in the difference between involved and uninvolved Free Light Chain levels and the absolute increase > 100mg/L |
* where immeasurable by SPE, 24h UPE or quantitative immunoglobulin analysis
British Committee for Standards in Haematology (BCSH) Guidelines
UK Myeloma Forum and the Nordic Myeloma Study Group:
Guidelines on the Diagnosis and Management of Multiple Myeloma 2005.
British Journal of Haematology 2006 132:410-451
Page 412
"Quantification of serum-free immunoglobulin light chain levels (FLC assay) and κ/λ ratio can be used as an alternative to quantifying urinary light chains. The serum tests are particularly useful for diagnosis and monitoring light chain only myeloma (Bradwell et al, 2003) and patients in whom the serum and urine is negative on immunofixation (non-secretory myeloma) (Drayson et al, 2001)."
Page 416
"Serum FLC assays are useful for monitoring FLC only and non-secretory myeloma (Drayson et al, 2001; Bradwell et al, 2003). FLC assay has also recently been shown to be helpful in monitoring response in the majority of patients with an intact immunoglobulin paraprotein; because of the short half-life of FLC this may provide an earlier indication of response to therapy than changes in intact paraprotein concentration (Mead et al, 2004)."
2005 Published Guidelines
Definition of Organ Involvement and Treatment Response in Immunoglobulin Light Chain Amyloidosis (AL): A Consensus Opinion From the 10th International Symposium on Amyloid and Amyloidosis3.
Morie A. Gertz, Ray Comenzo, Rodney H. Falk et al.
American Journal of Hematology 2005 79:319-328.
Abstract
"We undertook this study to develop uniformly accepted criteria for the definition of organ involvement and response for patients on treatment protocols for immunoglobulin light-chain amyloidosis (AL). A consensus panel was convened comprising 13 specialists actively involved in the treatment of patients with amyloidosis. Institutional criteria were submitted from each, and a consensus was developed defining each organ involved and the criteria for response. Specific criteria have been developed with agreed on definitions of organ and hematologic response as a result of discussions at the 10th International Symposium on Amyloid and Amyloidosis held in Tours, France, April 2004. These criteria now form the working definition of involvement and response for the purposes of future data collection and reporting. We report criteria that centers can now use to define organ involvement and uniform response criteria for reporting outcomes in patients with light-chain AL."
Page 320 - Section - How is the amyloidosis characterized as AL type?
"All patients should have an immunonephelometric immunoglobulin serum-free light chain assay."
Page 325 - Section - Hematologic (Immunochemical) Response Criteria
"The use of the serum free light chain assay has been important for quantification of hematologic responses and has been proposed as a useful tool to define hematologic response."
2004 Published Guidelines
British Committee for Standards in Haematology (BCSH) Guidelines
UK Myeloma Forum:
Guidelines on the Diagnosis and Management of AL Amyloidosis4.
British Journal of Haematology 2004 125:681-700
"Monoclonal immunoglobulins are often difficult to detect..............using traditional methods. The limitations of and inaccuracies using electrophoresis etc, are therefore self-evident, and the use of fully quantifiable serum FLC measurements are strongly encouraged."
The serum free light chain assay "appears to be the most effective method for monitoring clonal disease in AL patients."
"Treatment strategies in individual patients are presently best guided by their early effect on quantifiable measurements of circulating free immunoglobulin light chains"
For other BCSH guidelines, go to www.bcshguidelines.com and select Current Guidelines.
