Risk modifiers of immune-related adverse events in patients with NSCLC undergoing immunotherapy: a retrospective cohort study

Abstract Background To investigate immune-related adverse events (irAEs) in patients with non-small cell lung cancer receiving immune checkpoint inhibitor (ICI) therapy, and to identify clinical factors associated with irAE onset, thus supporting safer immunotherapy through effective monitoring. Methods This retrospective cohort study was conducted at Tohoku Medical and Pharmaceutical University Hospital over approximately 5 years. Hospitalized patients with non-small cell lung cancer who received immune checkpoint inhibitors for the first time were included. Physicians and pharmacists evaluated the occurrence, severity, and timing of irAEs. Cox proportional hazards regression and Fine–Gray competing risk analyses were performed to identify factors associated with irAE development. Results Among the 203 enrolled patients, 92 (45.3%) experienced irAEs, totaling 110 events. The most common irAE was interstitial lung disease (23 cases, 20.9%), followed by thyroid dysfunction (20 cases, 18.2%). In multivariable Cox regression analysis, comorbid heart failure was significantly associated with a reduced risk of irAE development (hazard ratio, 0.299; 95% confidence interval CI, 0.135–0.663; p = 0.003), and this association remained significant in the Fine–Gray competing risk model (subdistribution hazard ratio, 0.335; 95% CI, 0.147–0.766; p = 0.009). To address potential multicollinearity, an alternative model incorporating regular use of renin–angiotensin–aldosterone system inhibitors in place of comorbid heart failure also demonstrated a significant association with irAE incidence. Conclusions In this Japanese non-small cell lung cancer cohort, comorbid heart failure emerged as a potential modifier of irAE incidence, suggesting that baseline cardiac conditions may influence susceptibility to immune‑related toxicity. These findings underscore the importance of incorporating comorbidity profiles into individualized irAE monitoring strategies during cancer immunotherapy.