Severe immune-related adverse events in the neoadjuvant and adjuvant setting.

e24184 Background: Immune checkpoint inhibitors (ICIs) are increasingly used in early-stage cancers in the peri-operative setting. Yet while severe immune related adverse events (irAEs) are well-characterized in the metastatic setting, less is known about the presentations and outcomes of severe irAEs, particularly those requiring hospitalization, in neoadjuvant and adjuvant settings. Methods: This retrospective cohort study included patients hospitalized at Massachusetts General Hospital (MGH) and diagnosed with severe irAEs related to neoadjuvant ICI (regardless of whether they ultimately underwent surgery) or adjuvant ICI from 2/2011 to 4/2025. Patients were identified via institutional pharmacy records linked to hospital admission databases. Chart review was performed to collect demographics and characterize irAEs. Results: From 2/2011 to 4/2025, 87 patients were admitted to MGH for severe irAEs in the setting of neoadjuvant or adjuvant ICI. Of those, 29 (33.3%) had hospitalizations attributable to irAEs in the neoadjuvant setting and 58 (66.7%) to irAEs in the adjuvant setting. The most common cancers were melanoma (37.9%), lung (25.3%), and breast (16.1%). Most patients had stage II (19.5%) or III (67.8%) cancers, and most (83.9%) received anti-PD(L)1 therapy. Among the study cohort of 87 patients admitted with severe irAEs, the most common irAEs were endocrine (27.6%), gastrointestinal (21.8%), liver (19.5%), and cardiac (19.5%), and 29.9% of patients experienced multiple severe irAEs. Most patients had grade 3 irAEs (86.2%), but there was also a subset with grade 4 (10.3%) or 5 (2.3%) irAEs. Regarding irAE timing, most patients presented within 6 months of ICI initiation (66.7%), though 21.8% presented between 6-12 months, and 11.5% over 12 months after ICI initiation. Among 71 patients with non-endocrine irAEs, 94.4% received systemic steroids and 53.5% second-line immunosuppression. Premature ICI discontinuation due to irAEs occurred in 80.5% of 82 patients with non-fatal hospitalizations. Of 26 neoadjuvant patients with non-fatal hospitalizations, the majority (84.6%) underwent surgical resection (decisions to forego surgery were unrelated to irAEs); of those, 27.3% experienced an irAE-associated surgical delay (median delay 21 days, IQR 11 – 45.3). Among 82 total patients with non-fatal hospitalizations, 18.3% were re-challenged with ICI, 7.3% peri-operatively and 12.2% upon cancer recurrence. Of the 82 patients with non-fatal hospitalizations, 62.2% developed chronic irAEs (i.e. irAEs persisting ≥12 weeks). Conclusions: Severe irAEs requiring hospitalization represent a consequential source of morbidity among patients receiving neoadjuvant or adjuvant ICI and carry risks for mortality, surgical delay, premature ICI discontinuation, and chronic toxicity. Characterizing severe irAEs in the curative intent setting is crucial not only for acute management, but also for survivorship.