Immune-related adverse events and associated clinical outcomes in cancer patients treated with immune checkpoint inhibitors: A multicenter real-world study.

Abstract

e24149 Background: Immune checkpoint inhibitors (ICIs) are widely used in cancer treatment to boost the immune system's ability to target cancer cells. However, this can also induce immune-related adverse events (irAEs), which may impair organ function and affect patients' quality of life. Understanding the real-world impact of these irAEs is crucial. The primary outcome was to estimate the incidence and timing of side effects of ICIs. The secondary outcome was to assess and identify the pattern of irAEs and patient-disease-related factors associated with irAEs, time to onset of irAEs, and clinical outcomes. Methods: We conducted multi-centre retrospective cohort study in two large tertiary care centres at Riyadh, Saudi Arabia. We examined the use of ICIs in cancer patients aged 18 and older who received at least one dose of ICI between January 2017 and January 2023. Patients were followed until July 2025, death, or last documented clinical follow-up, whichever occurred first. Data, including demographics, clinical details, and treatment information, were extracted from electronic medical records (EMR). Results: A total of 608 patients were included (median age 62 [50–71] years; 55.9% male). The most common cancers were lung (118; 19.4%) and liver (85; 14.0%). Stage IV disease was present in 469 (77.1%), and metastases in 454 (74.7%). Pembrolizumab (307; 50.5%) and Nivolumab (185; 30.4%) were the most frequently used ICIs; and 305 (50.2%) patients received combination chemotherapy. Overall, 360 (59.2%) patients developed at least one irAE. The most frequent irAEs were fatigue (145; 23.8%), endocrine irAEs (93; 15.3%, mainly hypothyroidism 87; 14.3%), skin reactions (62; 10.2%), and colitis (54; 8.9%). Median time to irAEs onset was 84 [37–181] days; neurologic irAEs occurred earliest 20 [9–74] days, and endocrine irAEs occurred latest 135 [82–252] days. Disease progression occurred in 351 (57.7%) and was more frequent without irAEs (63.7% vs 53.6%, p =0.0132). The median progression-free survival (PFS) was 13.53 months (95%CI, 11.04–19.12) with irAEs versus 5.95 months (95%CI, 4.37–7.92) without irAEs (log-rank p <0.0001). The median overall survival (OS) was 23.85 months (95%CI, 18.73–37.88) with irAEs versus 17.67 months (95%CI, 14.06–28.94) without irAEs (log-rank p =0.176). Conclusions: In this large real-world study, irAEs were prevalent among patients receiving ICIs and showed variation in both time and organ involvement. Patients who experienced irAEs demonstrated prolonged PFS, although OS was numerically prolonged but did not achieve statistical significance. Overall, these findings highlight the clinical importance of recognizing and monitoring irAEs during ICI treatment in routine practice and its clinical implications.