Correlation between multiorgan immune-related adverse events and clinical outcomes in patients with extensive-stage small cell lung cancer (ES-SCLC) treated with chemo-immunotherapy.

e20129 Background: The addition of immune checkpoint inhibitors (ICIs) to platinum-based chemotherapy (CT-IO) has changed the first-line (1L) treatment landscape of extensive-stage small-cell lung cancer (ES-SCLC). Although ICIs improve survival, they can trigger immune related adverse events (irAEs). Notably, a correlation between irAEs and improved survival (OS) has been observed in several solid tumours including NSCLC. The impact of multiorgan irAEs in ES-SCLC treated with 1L CT-IO remains less clear. Methods: We retrospectively reviewed pts with ES-SCLC who received 1L CT-IO from November 2019 to September 2023 across 2 European centres. Demographic and clinical data were collected and analysed. We evaluated the correlation between irAEs (single and multiorgan) and OS. Results: A total of 217 pts were included. Median follow-up in censored pts was 13.2 m. Overall response rate was 75.1%, median PFS was 6.2 months (m) (95% CI, 5.8 - 6.7), and median OS 10.9 m (95% CI, 9.3 - 12.4). Single-organ any grade irAEs were reported in 58 pts (26.7%), while multi-organ irAEs occurred in 18 pts (8.3%). Clinicopathological characteristics stratified by irAEs are shown in the table. The most commonly affected organs were skin (n=25, 11.5%) and the digestive system (n=15, 6.9%). Treatment discontinuation rate due to irAEs was 11.1% (n=26). Median PFS in pts with multiorgan vs single vs no irAEs was 16.7m, 9.0m and 5.5m, respectively. Median OS was not reached, 17.9m and 8.2m, respectively. The multivariate analysis including irAEs as a time-varying covariate confirmed the association between irAEs and improved PFS (HR 0.38; 95% CI, 0.28 - 0.50, p<0.001) and OS (HR 0.37; 95% CI, 0.27-0.52, p<0.001). Conclusions: Our cohort shows that the incidence of irAEs in this setting is similar to previous real-world studies and that multiorgan irAEs were significantly associated with longer PFS and OS. Further research is needed to characterize the profile of irAEs associated with improved outcomes and to understand the role of concurrent therapeutic interventions. [Table: see text]