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Circulating free light chain measurement in the diagnosis, prognostic assessment and evaluation of response of AL amyloidosis: comparison of Freelite and N latex FLC assays

  • Giovanni Palladini , Arnaud Jaccard , Paolo Milani , David Lavergne , Andrea Foli , Sebastien Bender , Francesca Lavatelli , Tiziana Bosoni , Veronica Valentini , Laura Pirolini , Giovanni Ferraro , Marco Basset , Francesca Russo , Mario Nuvolone , Riccardo Albertini , Michel Cogne and Giampaolo Merlini EMAIL logo
Published/Copyright: March 27, 2017
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 55 Issue 11

Abstract

Background:

The measurement of circulating free light chain (FLC) is essential in the diagnosis, prognostic stratification and evaluation of response to therapy in light chain (AL) amyloidosis. For more than 10 years, this has been done with an immunonephelometric assay based on polyclonal antibodies (Freelite), and cutoffs for staging and response assessment have been validated with this method. Recently, a new assay based on monoclonal antibodies (N latex FLC) has been marketed in Europe.

Methods:

We evaluated and compared the clinical performance of the two assays in 426 patients with newly diagnosed AL amyloidosis.

Results:

We found suboptimal agreement between the two methods, with differences between values obtained with the Freelite and N latex FLC assays increasing with the concentration of clonal FLC. The diagnostic sensitivity of the Freelite (82%) and N latex FLC (84%) assays was similar, and both improved to 98% in combination with serum and urine immunofixation. The concentration of FLC measured with both methods had prognostic significance. Less pronounced decreases in FLC best predicted improved survival with the N latex FLC assay (33% vs. 50%), and there was poor concordance (84%) in discrimination of responders.

Conclusions:

The two assays have similar diagnostic and prognostic performance. However, they are not interchangeable, and follow-up should be done with either one. New response criteria are needed for the N latex FLC assay.

Keywords: amyloidosis; diagnosis; free light chain; prognosis; response
Corresponding author: Prof. Giampaolo Merlini, MD, Amyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo, Viale Golgi, 19, 27100 Pavia, Italy; and Department of Molecular Medicine, University of Pavia, Pavia, Italy

Acknowledgments

The authors are grateful to The Binding Site and Siemens for providing reagents. This study was supported in part by grant from “Associazione Italiana per la Ricerca sul Cancro – Special Program Molecular Clinical Oncology 5 per mille n. 9965”, from CARIPLO “Structure-function relation of amyloid: understanding the molecular bases of protein misfolding diseases to design new treatments n. 2013-0964”, and from CARIPLO “Molecular mechanisms of Ig toxicity in age-related plasma cell dyscrasias n. 2015-0591.”

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: GM, honoraria from The Binding Site and Siemens.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2016-11-7
Accepted: 2017-2-23
Published Online: 2017-3-27
Published in Print: 2017-10-26

©2017 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2016-1024
Keywords for this article
amyloidosis; diagnosis; free light chain; prognosis; response

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. High-sensitivity assays for cardiac troponins – continued
  4. Reviews
  5. The 99th percentile of reference population for cTnI and cTnT assay: methodology, pathophysiology and clinical implications
  6. Vitamin B1 in critically ill patients: needs and challenges
  7. Opinion Papers
  8. Point
  9. High-sensitivity cardiac troponin: do think twice, it’s not all right
  10. Counterpoint
  11. Terminology of cardiac troponin assays and data censoring
  12. Establishing consensus-based, assay-specific 99th percentile upper reference limits to facilitate proper utilization of cardiac troponin measurements
  13. Fast track protocols using highly sensitive troponin assays for ruling out and ruling in non-ST elevation acute coronary syndrome
  14. Genetics and Molecular Diagnostics
  15. Relationship between polymorphisms in the CRP, LEP and LEPR genes and high sensitivity C-reactive protein levels in Spanish children
  16. General Clinical Chemistry and Laboratory Medicine
  17. An approach for estimating measurement uncertainty in medical laboratories using data from long-term quality control and external quality assessment schemes
  18. Selecting multi-rule quality control procedures based on patient risk
  19. Moving sum of number of positive patient result as a quality control tool
  20. Multidisciplinary training activities for decreasing preanalytical mistakes in samples from primary care
  21. Harmonization protocols for TSH immunoassays: a multicenter study in Italy
  22. Circulating free light chain measurement in the diagnosis, prognostic assessment and evaluation of response of AL amyloidosis: comparison of Freelite and N latex FLC assays
  23. Serum prolactin revisited: parametric reference intervals and cross platform evaluation of polyethylene glycol precipitation-based methods for discrimination between hyperprolactinemia and macroprolactinemia
  24. Temporal and regional variability in the request of vitamin D from general practitioners in Spain
  25. Fibrinogen determination according to Clauss: commutability assessment of International and commercial standards and quality control samples
  26. Reference Values and Biological Variations
  27. S100B maternal blood levels are gestational age- and gender-dependent in healthy pregnancies
  28. Gestational age-specific reference intervals for serum thyroid hormone levels in a multi-ethnic population
  29. Cancer Diagnostics
  30. Serum complexed and free prostate-specific antigen (PSA) for the diagnosis of the polycystic ovarian syndrome (PCOS)
  31. Cardiovascular Diseases
  32. A new immunochemistry platform for a guideline-compliant cardiac troponin T assay at the point of care: proof of principle
  33. Diabetes
  34. Adiponectin and leptin as first trimester markers for gestational diabetes mellitus: a cohort study
  35. Letters to the Editor
  36. Can we still trust hemoglobin A1c in all situations?
  37. Automated detection of unstable hemoglobin variants by Sysmex XE-Series analyzers
  38. Mean hemoglobin concentrations in fasting venous and non-fasting capillary blood of Cambodian women using a hemoglobinometer and an automated hematology analyzer
  39. Evaluation of a POCT device for C-reactive protein, hematocrit and leukocyte differential
  40. New perspectives on existing data in comparative measurements: a simple extension of the regression analysis
  41. Evaluation of a human anti-mouse antibody rapid test for patients requiring radio-immunodiagnostic
  42. The cortisol-CBG ratio affects cortisol immunoassay bias at elevated CBG concentrations
  43. Prognostic value of total antioxidant capacity to predict functional outcome in traumatic brain injury patients
  44. Use of IFCC guidelines to verify acetylcholinesterase reference interval in adults determined with ChE check mobile testing system
  45. Congress Abstracts
  46. 49th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC – Laboratory Medicine)
  47. Congress of Clinical Chemistry and Laboratory Medicine
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