Analytical validation and clinical concordance of Diazyme free light chain assays on the Cobas® platform compared...

Serum free light chains (FLC) are key biomarkers for the diagnosis and monitoring of plasma cell dyscrasias. Current International Myeloma Working Group (IMWG) recommendations are based on Freelite™ assays. This study aimed to evaluate the analytical performance and clinical concordance of Diazyme κ and λ FLC assays on the Roche Cobas® platform in comparison with Freelite™. A total of 660 serum samples from patients with multiple myeloma, MGUS/smoldering myeloma, Waldenström macroglobulinemia, AL amyloidosis, and other gammopathies were analyzed. Precision, reference intervals, and method comparison were assessed according to CLSI EP05-A3 and EP09-A3 guidelines. Statistical analyses included Passing-Bablok regression, Bland-Altman analysis, Pearson correlation, and evaluation of clinical concordance. Within-run and total imprecision showed coefficients of variation ≤ 6%. Reference intervals for the κ/λ ratio were 0.22-2.25 in healthy individuals and 0.30-2.75 in patients with renal insufficiency. Method comparison demonstrated strong agreement with Freelite™ for κ (y = 0.95x + 0.34, R² = 0.96), λ (y = 0.90x + 4.1, R² = 0.91), and κ/λ ratio (r = 0.92). Overall clinical concordance was 96%, with discrepancies mainly observed near decision thresholds. Diazyme κ and λ FLC assays on the Cobas® platform show excellent analytical performance and high clinical concordance with Freelite™, supporting their use in routine laboratory practice, with applicability to IMWG-based interpretation.