Recurrent Cytokine Release Syndrome in Metastatic Gastric Cancer on Nivolumab-FOLFOX: A Case Report and Mechanistic Review.

INTRODUCTION

Cytokine release syndrome (CRS) is a hyperinflammatory condition most commonly observed following chimeric antigen receptor (CAR)-T cell therapy in haematological malignancies. However, it remains rare and under-recognised in solid tumours.

CASE PRESENTATION: We describe an 86-year-old woman with metastatic gastric adenocarcinoma treated with FOLFOX chemotherapy and nivolumab immunotherapy who developed recurrent episodes of CRS. Following the third and fourth treatment cycles, she presented with fever, confusion, abdominal pain, lymphadenopathy, leucocytosis, and acute kidney injury, with negative cultures and imaging. Both episodes resolved rapidly with supportive care alone. The recurrence of symptoms despite withholding granulocyte colony-stimulating factor (G-CSF) implicated chemoimmunotherapy as the likely trigger.

CONCLUSION

This case highlights the diagnostic challenges posed by CRS, particularly its overlap with sepsis and other immune-related adverse events. We propose a dual mechanism in which cytotoxic chemotherapy amplifies immune checkpoint inhibitor-driven T-cell activation through tumour antigen release. Here, the reproducible treatment-linked pattern and resolution after stopping nivolumab supports an immune-mediated aetiology. Clinicians should maintain a high index of suspicion for CRS when evaluating gastric cancer patients presenting with fever and systemic inflammation after immunotherapy, as awareness is essential for timely recognition, differentiation from infection, and personalised management.