# Rhinosinusitis as an Immune-Related Adverse Event: Clinical Characteristics, Management, and Prognostic Implications in Metastatic Melanoma Patients

## TL;DR

Rhinosinusitis, a largely asymptomatic immune-related side effect in melanoma patients treated with immunotherapy, is linked to improved survival and may serve as a biomarker for better outcomes.

## Contribution

This study identifies rhinosinusitis as a novel biomarker of favorable prognosis in metastatic melanoma patients undergoing immune checkpoint inhibitor therapy.

## Key findings

- Rhinosinusitis occurred in 21.1% of patients and was associated with a doubling of median overall survival in metastatic melanoma.
- The condition was most common with nivolumab monotherapy and significantly linked to eosinophilia.
- Rhinosinusitis was aseptic and largely asymptomatic, with no significant survival benefit in the adjuvant setting.

## Abstract

The present study focuses on one such underrecognized, immune-related adverse event—rhinosinusitis. Through a retrospective analysis of 304 melanoma patients treated with immune checkpoint inhibitors, we identified a significant association between imaging-confirmed rhinosinusitis and improved overall survival in the metastatic setting. Notably, rhinosinusitis occurred in over 20% of patients, was significantly linked to eosinophilia, and appeared most frequently with nivolumab monotherapy. Despite being largely asymptomatic and aseptic, its presence correlated with a doubling of median overall survival from ICI initiation. Our findings suggest that rhinosinusitis may serve as a novel biomarker of therapeutic response and favorable prognosis in metastatic melanoma patients undergoing ICI therapy. We believe this study offers a meaningful contribution to the growing field of immunotoxicology and may prompt further exploration of sinonasal inflammation in immunotherapy-treated populations.

Background: Melanoma management has been revolutionized by the use of immune checkpoint inhibitors (ICIs). However, ICIs are associated with immune-related adverse events (irAEs), including rhinosinusitis, which remains underexplored. This study evaluated the incidence, characteristics, management, and prognostic implications of rhinosinusitis in patients with melanoma under ICIs. Methods: A retrospective analysis was conducted on adult patients with melanoma treated with ICIs. Demographic, clinical, laboratory, treatment, and survival data were collected. Rhinosinusitis was defined radiographically and graded using the Harvard scoring system. Associations between rhinosinusitis and survival outcomes were analyzed. Results: Among 304 patients, 64 (21.1%) developed imaging-confirmed rhinosinusitis during ICI treatment, with 9.4% symptomatic cases. Rhinosinusitis was the sole irAE in 11.8% of patients, and 9.2% experienced it alongside other irAEs. A significant correlation with eosinophilia was observed: 39.6% of eosinophilic patients developed rhinosinusitis versus 17.1% without eosinophilia (p < 0.001). Most cases occurred during the first ICI line (86.4%), particularly with nivolumab monotherapy (32.8%). Importantly, in metastatic melanoma, rhinosinusitis was associated with significantly longer overall survival since ICI initiation (OSICI) compared to patients without rhinosinusitis (33.3 vs. 15.4 months, p = 0.025). No survival benefit was observed in the adjuvant setting. The condition was predominantly aseptic, and corticosteroids were used in 7.8%. Conclusions: This study highlights rhinosinusitis as an irAE associated with improved OS in metastatic melanoma. Further research is required to elucidate the underlying mechanisms and assess the resolution of rhinosinusitis after ICI discontinuation. Additionally, rhinosinusitis may serve as a marker of favorable prognosis in metastatic melanoma patients receiving ICIs.