Distribution of adverse effects of immune checkpoint inhibitors and their impact on survival: some with better but some with worse survival

According to the literature, immune- related adverse events (irAEs) occur in approximately 70% of patients receiving anti- PD-1/PD- L1 therapy. The most common irAEs are thyroiditis and skin toxicities. While some studies report a positive association between irAEs and survival, others find that certain irAEs are associated with worse survival and treatment interruption. Limited research has been conducted on this controversial topic; therefore, we aimed to conduct a comprehensive study on the relationship between irAEs and survival by analyzing data from our advanced-stage cancer patients receiving ICI (Immune checkpoint inhibitor) treatment in first- and second-line settings. This retrospective, single-center study included 300 patients with metastatic malignancy between January 2020 and January 2024. Our primary objective was to investigate the relationship between irAEs and survival. The Kaplan–Meier method and log-rank tests were used to compare OS and PFS durations between clinical groups. The independent t-test was used for pairwise comparisons between groups. Finally, multivariate Cox regression results on the risk of death for various clinical variables are presented. In patients without adverse events, the median overall survival (OS) was 9. 0 months (95% CI: 8. 01–9. 99), whereas in patients with adverse events, the median OS was 25. 0 months (95% CI: 23. 43–26. 26.56), and this difference was statistically significant ( p < 0. 001). Survival was significantly longer, particularly in patients who developed hypothyroidism, with a median OS of 41. 0 months (95% CI: 22. 98–59. 01), compared with 23. 0 months (95% CI: 21. 15–24. 84) in patients without hypothyroidism ( p < 0. 001). Similarly, the median OS was significantly longer in patients who developed skin toxicity, at 48. 0 months (95% CI: 21. 62–74. 37) ( p < 0. 001). Patients with elevated AST/ALT levels and pneumonitis had significantly shorter survival times ( p = 0. 015 and p < 0. 001, respectively). In contrast, the presence of mucositis, acute renal injury, arthritis, adrenal insufficiency, and hypophysitis did not show a statistically significant difference in OS. In conclusion, based on the available data, it can be stated that various side effects may occur during treatment with ICI agents, and these side effects can serve as indicators of treatment response and survival. In our study, we found that some irAEs positively affected survival, some negatively affected survival, and some did not affect survival. Although the number of studies on this subject remains relatively small, we suggest that survival can be predicted by monitoring irAEs. Larger, multicenter studies are needed.