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Clinical Trial
. 2018 Jul 13;19(1):178.
doi: 10.1186/s12882-018-0962-x.

Serum Free Light Chain Levels and Renal Function at Diagnosis in Patients With Multiple Myeloma

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Free PMC article
Clinical Trial

Serum Free Light Chain Levels and Renal Function at Diagnosis in Patients With Multiple Myeloma

Punit Yadav et al. BMC Nephrol. .
Free PMC article

Abstract

Background: Renal impairment (RI) is common in multiple myeloma (MM) and is associated with poor survival. This study reports the associations between renal function and disease characteristics including serum free light chain (FLC) level at diagnosis in patients with MM.

Methods: Using data from the Medical Research Council Myeloma IX trial, a multicentre, randomized, open-label, phase III and factorial-design trial, we assessed the relationships between renal function, demographic, and disease characteristics, including serum FLC levels, in 1595 newly diagnosed MM patients. Multivariable linear regression was utilised to identify factors that were associated with renal function at diagnosis. A receiver operating characteristic curve (ROC) was used to identify the optimal threshold for serum FLC level at diagnosis to predict severe RI.

Results: 52.8% of patients had an estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 (no RI), 37.3% an eGFR 30-59 ml/min/1.73 m2 (mild to moderate RI), and 9.8% an eGFR < 30 ml/min/1.73 m2 (severe RI). In a multivariable analysis, factors independently and negatively associated with eGFR at diagnosis were: higher serum FLC level, female gender, and older age. Elevated serum FLC level at diagnosis, irrespective of the paraprotein type, was strongly associated with severe RI. Receiver operating characteristic curve analysis showed a serum FLC level of > 800 mg/L as the optimal cut-off associated with severe RI (area under curve 0.86, 95% confidence interval 0.77-0.84).

Conclusion: There was a strong relationship between higher serum FLC levels at diagnosis and the severity of RI that was irrespective of the paraprotein type. We report an increased risk of severe RI in patients presenting with serum FLC levels above 800 mg/L at diagnosis.

Keywords: Myeloma; Renal impairment; Serum free light chain level.

Conflict of interest statement

Ethics approval and consent to participate

MRC Myeloma IX trial had a multicentre research ethics committee and local ethics committee’s approval and all patients gave written informed consent in accordance to the Declaration of Helsinki (International Standard Randomised Controlled Trial Number 68454111).

Consent for publication

Not applicable.

Competing interests

University of Birmingham and MTD own shares in Abingdon Health that manufactures immunodiagnostic tests to quantify FLC levels. PC is a medical advisor to The Binding Site that produces the Freelite assay. The remaining authors have no competing financial interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
CONSORT diagram showing patient distribution by renal function. (MRC, Medical Research Council)
Fig. 2
Fig. 2
Serum FLC level distribution by eGFR. (showing a progressive rise in serum FLC level with worsening of eGFR category irrespective of the FLC isotype. Data presented as box plot with whiskers and solid line represents median)
Fig. 3
Fig. 3
Involved serum FLC level by paraprotein type. (data presented as box plot with whiskers where solid line represents median)
Fig. 4
Fig. 4
eGFR distribution across serum FLC level categories. (depicting increase in proportion of patients presenting with severe RI as serum FLC level at diagnosis rises above 800 mg/L)
Fig. 5
Fig. 5
Receiver operating characteristic (ROC) curve testing association between FLC level and eGFR < 30 ml/min/1.73m2. (AUC, area under curve; CI, confidence interval)

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