Association of Sinonasal Symptoms and Disease With Immune Checkpoint Inhibitor Therapy

Immune checkpoint inhibitors (ICIs) are widely used for cancer therapy and are associated with immune-related adverse events (irAEs) in various organ systems. However, data on sinonasal irAEs remain limited. This study investigates the association between ICI therapy and sinonasal conditions, including chronic rhinosinusitis (CRS) and nasal polyps, using a national health database.

This retrospective cohort study utilized the TriNetX US Network to analyze adults diagnosed with malignant neoplasms for which ICIs are an accepted treatment option. Patients treated with FDA-approved ICIs (pembrolizumab, nivolumab, cemiplimab, atezolizumab, durvalumab, avelumab, or ipilimumab) were compared to those not receiving ICIs. Exclusion criteria included sinonasal neoplasms and prior sinus surgery. Propensity score matching on age, race, sex, and asthma diagnosis was performed. Outcomes included first-time diagnoses of CRS, nasal polyps, and cardinal symptoms of CRS. Subgroup analyses by ICI mechanism of action and a post hoc analysis of all-cause mortality were conducted.

ICI therapy was associated with a decreased likelihood of CRS diagnosis (OR 0.90, 95% CI 0.85-0.96), nasal polyp diagnosis (OR 0.65, 95% CI 0.51-0.83), and facial pain (OR 0.74, 95% CI 0.56-0.99). Conversely, patients receiving ICIs had an increased likelihood of anosmia/parosmia or parageusia (OR 1.86, 95% CI 1.68-2.07), and rhinorrhea (OR 1.16, 95% CI 1.10-1.22). Subgroup analyses supported these findings across different ICI categories. Risk of mortality was higher among ICI-treated patients (HR 4.09, 95% CI 4.02-4.16).

This is the first propensity-matched study to evaluate the relationship between ICI therapy and sinonasal conditions, revealing a decreased risk of CRS and nasal polyps in patients undergoing ICI therapy. Future studies are needed to explore the clinical significance and mechanism of ICI-related sinonasal symptoms.

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