Abstract

BackgroundRenal 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.MethodsUsing 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.Results52.8% 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).ConclusionThere 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.

Highlights

  • Renal impairment (RI) is common in multiple myeloma (MM) and is associated with poor survival

  • Patient demographics and renal function 1966 patients with newly diagnosed symptomatic MM were recruited in the Medical Research Council (MRC) Myeloma IX trial; 1112 (56.6%) were assigned to the intensive arm and 854 (43.4%) to the non-intensive arm of the trial (Fig. 1)

  • There was a significant association between age at diagnosis and the severity of RI (P < 0.001); patients with RI were older compared to patients with no RI

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Summary

Introduction

Renal impairment (RI) is common in multiple myeloma (MM) and is associated with poor survival. Renal impairment (RI), as defined by an estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73m2, is present in up to 50% of patients with multiple myeloma (MM) and is associated with a poor prognosis [1, 2]. The commonest cause of severe RI at diagnosis (estimated glomerular filtration rate (eGFR) < 30 ml/ min/1.73m2) is through nephrotoxicity of the secreted immunoglobulin free light chain (FLC); this can be potentially reversed by the rapid lowering of the involved FLC with effective anti-myeloma therapy [5,6,7].

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