Immune‐Related Polyradiculoneuropathy Associated With Immune Checkpoint Inhibitors: A Comprehensive Case Series

OBJECTIVE: Immune-related polyradiculoneuropathy (irPRN) is a rare but potentially severe neurological adverse event secondary to immune checkpoint inhibitors (ICIs), closely resembling Guillain-Barré syndrome. This study aims to characterize the clinical presentation, neurophysiological findings, therapeutic strategies, and clinical outcomes of patients diagnosed with irPRN. METHODS: We conducted a retrospective single-center study including patients diagnosed with irPRN following ICI therapy between May 2018 and July 2024. Clinical, electrophysiological, and cerebrospinal fluid (CSF) data were analyzed. RESULTS: Nine patients (mean age 67.9 years; 66.7% male) developed immune-related polyradiculoneuropathy (irPRN), with a median onset of 6 weeks following initiation of immune checkpoint inhibitors (ICIs). Most cases (66.7%) occurred in patients receiving anti-PD-1 monotherapy. The clinical presentation was characterized by symmetric limb weakness (100%) and sensory disturbances (88.9%). Electrodiagnostic studies demonstrated a demyelinating polyradiculoneuropathy in 8 of 9 patients; only one exhibited an axonal pattern. CSF analysis revealed elevated protein levels in all tested patients, with mild pleocytosis in 62.5%. At nadir, the modified Rankin Scale (mRS) ranged from 3 to 5. Immunomodulatory therapy was administered in 8 of 9 patients (88.9%), leading to notable functional improvement (mRS 1-2) in five cases. ICI rechallenge was attempted in two patients, neither of whom experienced recurrence. No deaths were directly attributed to irPRN. CONCLUSION: IrPRN is a rare but distinct complication of ICI therapy, typically presenting with a demyelinating neurophysiological pattern and favorable response to immunotherapy. Early recognition and treatment are critical to improving functional outcomes. Rechallenge may be feasible in selected cases without recurrence.