P-092: High Serum Free Light Chains levels in African Ancestry population screened for Monoclonal Gammopathy: implication for definition of FLC Reference Range Accounting for Renal Function and Race

Introduction: Serum free light chains (sFLC) are important for diagnosis and prognosis of plasma cell dyscrasias and are known to be affected by kidney function and inflammation. In a biobanked population, African Americans (AA) were reported to have significantly higher Kappa (κ) and Lambda (λ) sFLC after adjusting for kidney function. We hypothesize that adjusted sFLC reference ranges are needed for individuals of African and European descent.

Methods: We analyzed serum from 738 healthy Black South African (SA) and 3402 US individuals (AA+EA) as part of a study screening individuals at high risk of multiple myeloma (MM) and precursors (self-identify as Black or with family history of blood cancer). sFLC levels were measured using the Optilite® Freelite assay (The Biding Site). Participants were screened for Monoclonal Gammopathy of Undetermined Significance (MGUS; M protein ≥ 0.2 g/L) by MALDI-TOF mass spectrometry. Serum Cystatin C (Optilite®) was used to calculate estimated Glomerular Filtration Rate (eGFR) with CKD-EPI Cystatin C Equation (2012) formula for 752 individuals. Group medians were compared with Wilcoxon tests. Abnormal sFLCr was defined as a value outside the reference range with involved sFLC above the manufacturer’s reference range. We used the 95% central interval (CI) for new sFLCr reference ranges.

Results: After excluding individuals with Heavy Chain-MGUS, we included 654 SA, 326 AA, and 2,551 EA. Median age was 52, 56 and 58 respectively. Females were more common in the AA (74%) and EA (73%) vs SA (52%). Calculated median eGFR was 118 ml/min for SA and 112 for AA. HIV positivity was higher in SA (23%) than other groups ( < 1%), 99% of whom were under treatment (Tenofovir 92%).
The median free κ was higher in SA (32 mg/l,) than AA (18.1 mg/l,, +80%, p< 0.01) and EA (13.7 mg/l, +133%, p< 0.01). Similarly, median free λ was higher in SA (24.6 mg/l,) than AA (15 mg/l, , +64%, p< 0.01) and EA (11.9, mg/l, +106%, p< 0.01). 92% of SA, 43% of AA, and 16% of EA had κ values above the normal range. Similarly, 43% of SA, 10% of AA, and 3% of EA had λ values outside the normal range. Median sFLCr was higher in SA (1.34, IQR 1.13-1.65) than AA (1.25,p < 0.01), and EA (1.18, p< 0.01) (Fig 1). Using the standard manufacturer ranges, 25% of SA, 11% of AA and 3% of EA had abnormal sFLCr and involved FLC. In multivariate logistic regression higher age, HIV positivity, and lower eGFR were independent predictors of abnormal sFLCr for SA or AA compared to EA. In SA with normal renal function (eGFR >60 ml/min), excluding those with free κ and λ outside the 95% CI, we identified a new FLCr reference range of 0.80-2.38.

Conclusions: We observed a significantly higher sFLC for Black (SA and AA) than White individuals (EA), independent of renal function. This could be due to genetic background and social and environmental factors, like HIV infection. While further validation is needed, we propose a new sFLC range for African ancestry populations with normal renal function.