High serum sodium predicts immunotherapy response in metastatic renal cell and urothelial carcinoma

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Niklas Klümper1, Alexander Cox2, Markus Eckstein3

  • 1Department of Urology, University Hospital Bonn (UKB), Bonn, Germany; Center for Integrated Oncology Aachen/Bonn/Cologne/Düsseldorf (CIO-ABCD), Germany; Institute of Experimental Oncology, University Hospital Bonn (UKB), Bonn, Germany.

European Journal of Cancer (Oxford, England : 1990)
|May 4, 2024
PubMed
Abstract

Insights

Elevated serum sodium levels predict a better response to immune checkpoint inhibition (ICI) in metastatic renal cell carcinoma and urothelial carcinoma. This simple blood test may serve as a cost-effective biomarker for immunotherapy efficacy.

Area of Science:

  • Oncology
  • Immunotherapy
  • Biomarker Discovery

Background:

  • Predicting response to immune checkpoint inhibition (ICI) in metastatic renal cell carcinoma (mRCC) and urothelial carcinoma (mUC) is challenging.
  • Current biomarkers like PD-L1 focus on tumor factors, neglecting other potential predictors.
  • Serum electrolyte levels have been largely unexplored as predictive biomarkers for ICI response.

Purpose of the Study:

  • To evaluate the prognostic and predictive value of baseline serum electrolyte levels (sodium, potassium, chloride, magnesium, calcium) in patients with mRCC and mUC treated with ICI.
  • To compare the efficacy of serum electrolytes as biomarkers against conventional markers like PD-L1 expression.

Main Methods:

  • Post-hoc analysis of serum electrolyte levels from two independent phase 3 clinical trials (IMvigor211 and IMmotion151).
  • Analysis included 1787 patients with mRCC and mUC.
  • Prognostic and predictive values were assessed using multivariate analysis.

Main Results:

  • Baseline serum sodium and chloride levels showed a linear correlation with prognosis in both trials.
  • Elevated serum sodium (>140 mmol/L) was associated with a significantly higher objective response rate to ICI.
  • Serum sodium outperformed PD-L1 expression in predicting immunotherapy efficacy.

Conclusions:

  • Elevated baseline serum sodium levels are associated with superior outcomes in patients receiving immunotherapy.
  • Serum sodium concentration represents a promising, cost-effective predictive biomarker for immunotherapy response across different cancer types.
Keywords:
BiomarkersImmunotherapyRenal cell carcinomaSodiumUrothelial carcinoma

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