Immune-related adverse events in patients with mismatch repair–deficient gynecologic malignancies.

Abstract

e17534 Background: Immune checkpoint inhibitors (ICIs) have shown clinical efficacy in treating tumors that harbor mismatch repair deficiencies (dMMR). However, despite their clinical efficacy, these treatments carry a risk of immune-related adverse events (irAEs). In all patients with a gynecologic malignancy being treated with an ICI, the risk of adverse event of any grade is around 30-50%, with risk of a grade 3 or 4 event around 5-11%. We hypothesize that the rate of irAE may differ in frequency and severity among dMMR patients compared to those who are mismatch repair proficient. Methods: A retrospective review was conducted of patients with gynecologic malignancies harboring mismatch repair deficiency who received immune checkpoint inhibitor therapy at Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University Hospital and its affiliated sites. Patients who received their first dose of therapy between January 2020 and August 2025 were eligible. The primary outcome was the incidence and grade of immune-related adverse events. Secondary outcomes included progression-free survival (PFS) and overall survival (OS). Event rates in this cohort were descriptively compared with published literature reporting outcomes in patients with gynecologic malignancies irrespective of mismatch repair status. Results: A total of 89 patients were screened, and 52 met inclusion criteria. Among these 52 patients, 35 (67.3%) experienced at least one immune-related adverse event (irAE) of any grade. In total, 57 irAEs were reported, with 12 of the 35 affected patients (34%) experiencing involvement of more than one organ system. The most frequently affected organ systems were endocrine (31.6% of reported irAEs) and gastrointestinal (22.8%). Grade 3 or 4 events accounted for only 7% of all reported adverse events. No statistically significant differences in age or race were observed among patients who experienced adverse events. Median PFS and OS were not reached. Conclusions: The incidence of immune-related adverse events was higher in patients with dMMR gynecologic cancers than in gynecologic cancer patients overall, independent of mutational status; the frequency of grade 3 or 4 events was similar.