Early dynamics of eosinophils and the neutrophil-to-lymphocyte ratio are associated with severe immune-related adverse events during nivolumab therapy for metastatic renal cell carcinoma

@article{fiala2026early,
  title = {{Early dynamics of eosinophils and the neutrophil-to-lymphocyte ratio are associated with severe immune-related adverse events during nivolumab therapy for metastatic renal cell carcinoma}},
  author = {Ondřej Fiala and Jan Králíček and Jindřich Kopecký and Michal Vočka and Tomas Buchler and Hana Študentová and Jana Obertová and Beáta Rondzíková and Martin Matějů and Dominik Šafčák and Matej Hrnčár and Peter Priester and Martina Spisarová and Anežka Zemánková and Radka Lohynská and Michaela Tkadlecová and Lucie Grmelová and Petr Stránský and Bohuslav Melichar and Patrik Palacka and Alexandr Poprach},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1944728},
  url = {https://doi.org/10.3389/fimmu.2026.1944728},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - Early dynamics of eosinophils and the neutrophil-to-lymphocyte ratio are associated with severe immune-related adverse events during nivolumab therapy for metastatic renal cell carcinoma
AU  - Ondřej Fiala
AU  - Jan Králíček
AU  - Jindřich Kopecký
AU  - Michal Vočka
AU  - Tomas Buchler
AU  - Hana Študentová
AU  - Jana Obertová
AU  - Beáta Rondzíková
AU  - Martin Matějů
AU  - Dominik Šafčák
AU  - Matej Hrnčár
AU  - Peter Priester
AU  - Martina Spisarová
AU  - Anežka Zemánková
AU  - Radka Lohynská
AU  - Michaela Tkadlecová
AU  - Lucie Grmelová
AU  - Petr Stránský
AU  - Bohuslav Melichar
AU  - Patrik Palacka
AU  - Alexandr Poprach
PY  - 2026
DA  - 2026/10/12
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1944728
UR  - https://doi.org/10.3389/fimmu.2026.1944728
AB  - Background: Reliable biomarkers for characterization of the risk of severe immune-related adverse events (irAEs) during immune checkpoint inhibition remain lacking. We hypothesized that early dynamics of complementary complete blood count (CBC)-based immune biomarkers may be associated with severe immune toxicity. We therefore evaluated longitudinal changes in absolute eosinophil count (AEC) and neutrophil-to-lymphocyte ratio (NLR) in patients with metastatic renal cell carcinoma (mRCC) treated with nivolumab.  Methods: This multicenter retrospective study included 503 patients with mRCC receiving nivolumab monotherapy in the second or later treatment line. Biomarker analyses were performed using a prespecified 28-day landmark design. AEC and NLR were evaluated at baseline, month 1, and as dynamic Low→High phenotypes, defined as transition from below the baseline upper-quartile threshold to the highest month-1 quartile. Multivariable logistic regression adjusted for age, sex, ECOG performance status, IMDC risk group, and treatment line.  Results: Among 501 toxicity-evaluable patients, 57 (11.4%) developed grade 3–4 irAEs. Baseline AEC and NLR were not associated with severe irAEs. In contrast, the AEC Low→High phenotype was associated with severe irAEs after multivariable adjustment (adjusted odds ratio [aOR] 2.25, 95% confidence interval [CI] 1.02–4.97; P = 0.045), as was the NLR Low→High phenotype (aOR 2.77, 95% CI 1.25–6.17; P = 0.012). In a prespecified combined multivariable model, NLR remained independently associated with severe irAEs (aOR 2.81, 95% CI 1.25–6.30; P = 0.012), whereas the AEC association was attenuated (aOR 2.08, 95% CI 0.90–4.80; P = 0.085).  Conclusions: Early dynamics of eosinophils and NLR, rather than baseline biomarker values, were associated with severe irAEs during nivolumab therapy. These findings suggest that eosinophil expansion and inflammatory remodeling may reflect aspects of early immune activation associated with clinically significant immune toxicity. Longitudinal assessment of routinely available CBC-based immune biomarkers therefore warrants prospective validation in cohorts with time-resolved toxicity assessment.
SN  - 1664-3224
ER  -