# Immune checkpoint inhibitor-related encephalitis overlapping with hyperprogression in metastatic lung cancer: a case report

## TL;DR

A lung cancer patient developed brain inflammation and rapid tumor growth after treatment with immune checkpoint inhibitors, highlighting the need for careful monitoring.

## Contribution

This case report highlights the rare but serious co-occurrence of ICI-related encephalitis and hyperprogressive disease in a metastatic lung cancer patient.

## Key findings

- A patient with metastatic lung cancer developed subacute neurological decline and elevated IL-6 in cerebrospinal fluid after pembrolizumab therapy.
- Despite treatment for encephalitis, the patient experienced rapid tumor progression termed hyperprogressive disease.
- The case emphasizes the importance of early recognition and multidisciplinary management of rare immune-related adverse events during ICI therapy.

## Abstract

Immune checkpoint inhibitors (ICIs) have significantly improved survival in patients with advanced non-small cell lung cancer (NSCLC), but may rarely trigger severe immune-related adverse events (irAEs).

A 64-year-oldpatient with metastatic squamous NSCLC and high programmed death-ligand 1 (PD-L1) expression developed subacute neurological decline following pembrolizumab therapy, concurrent with rapid progression. Cerebrospinal fluid (CSF) analysis revealed inflammatory changes featuring markedly elevated IL-6 levels, while serological and imaging studies excluded infection, supporting a diagnosis of ICI-related encephalitis. Despite neurological symptom resolution with corticosteroids and intravenous immunoglobulin, systemic hyperprogressive disease (HPD) emerged, culminating in fatal tumor progression.

This case underscores the need for vigilance toward the coexistence of rare neurotoxic irAEs and HPD during ICI therapy. Early recognition, multidisciplinary collaboration, and balanced therapeutic strategies are critical to optimizing outcomes.