(PA-183) Bridging the Gap: Conversion of Siemens N-Latex to Binding Site Freelite for Accurate Multiple Myeloma Diagnosis and Risk Stratification

The International Myeloma Working Group (IMWG) defines myeloma-defining events (MDEs) using thresholds based on the Binding Site Freelite assay, including a free light chain (FLC) ratio >100. However, many institutions employ alternative assays, such as Siemens N Latex, which yield systematically lower values. Applying IMWG criteria directly to Siemens results may lead to underdiagnosis of active multiple myeloma. It also leads misclassification of risk of smoldering myeloma (SMM) which also uses a ratio of >20 as one of the risk factors, delaying necessary treatment.


Methods:   

We prospectively collected 2,094 paired FLC measurements from 1,772 patients between December 2023 and February 2024 using Siemens N Latex (BNII) and Binding Site Freelite (Optilite) platforms. After outlier exclusion, regression models were generated. Nonparametric comparisons and correlation matrices were used to validate concordance.


Results:   

Linear conversion equations were established for kappa (r=0.93), lambda (r=0.77), and kappa/lambda ratio (r=0.86). Regression analysis yielded the following:

Kappa: Siemens = 0.65 × Freelite + 0.44

Lambda: Siemens = 0.79 × Freelite + 1.07

Ratio: Siemens = 0.49 × Freelite + 0.34

A Freelite FLC ratio of 100 corresponds to approximately 50 using Siemens. Involved FLC thresholds of 10 mg/dL align with 7 mg/dL (kappa) and 9 mg/dL (lambda) on Siemens. Without assay-specific thresholds, nearly 50% of patients meeting IMWG diagnostic criteria using Freelite were misclassified with Siemens. Similarly, high-risk SMM patients with Freelite ratios >20 were under-identified on Siemens, potentially delaying early therapeutic intervention.


Conclusions:   

Using Freelite-based IMWG criteria with Siemens N Latex assay results introduces a substantial risk of missed multiple myeloma diagnoses and under-recognition of high-risk smoldering myeloma. A Siemens FLC ratio >50 should prompt confirmatory testing with the Binding Site Freelite assay before ruling out active disease. For SMM risk stratification, a Siemens FLC ratio >10 should be considered equivalent to a Freelite ratio >20 to ensure appropriate identification of patients who may benefit from early intervention. These findings highlight the urgent need for IMWG endorsed, assay-specific thresholds or mandatory reporting of assay platform to ensure consistent and accurate clinical decision-making.