Andreas V Koulouris, Ioannis P Trontzas, Ioannis A Vathiotis, Maria Effrosyni Livanou, Marcus Skribek, Emmanouil Panagiotou, Athanasios Trimis, Simon Ekman, Georgios Tsakonas, Konstantinos N Syrigos
In this bi-national cohort, overall and multisystem irAE rates were similar, but severe and selected organ-specific toxicities were more frequent in the Swedish population. Geographic and host-related factors may modulate irAE severity and should inform risk-adapted toxicity surveillance.
BACKGROUND: Immune-related adverse events (irAEs) are common complications of immunotherapy, yet real-world evidence on how irAE patterns vary across patients from different geoenvironmental or genetic backgrounds remains limited. Observed differences in autoimmune disease prevalence across European regions motivated an exploratory comparison of irAEs in two large ICI-treated non-small cell lung cancer (NSCLC) cohorts.
METHODS: We conducted a retrospective study of two independently assembled cohorts of consecutive patients with advanced NSCLC treated with immunotherapy at specialized thoracic oncology departments in Southern Europe (Sotiria Thoracic Diseases Hospital of Athens, Greece; 2014-2023) and Northern Europe (Karolinska University Hospital, Sweden; 2015-2022). Clinical characteristics, treatment patterns, and irAEs (CTCAE v5.0) were harmonized into a unified dataset. Descriptive statistics were reported and compared between the two cohorts. Multivariable logistic regression evaluated the independent association between cohort and (i) any irAE, (ii) multiple irAEs, and (iii) grade≥3 irAEs.
RESULTS: Of 1,331 included patients (653 Greek, 678 Swedish), treatment patterns were largely similar. Overall, irAE incidence did not differ significantly, nor did the rate of multiple irAEs. However, hepatitis and nephritis were more common in the Swedish population (11.4% vs. 5.7%, p = 0.0002; and 4.0% vs. 0.5%, p < 0.0001, respectively). Severe irAEs (grade≥3) were more frequent in Sweden (21.9% vs. 10.4%; p < 0.0001). In the multivariable analysis, irAEs severity remained significantly more prominent in the Swedish cohort (OR:2.04, 95%CI:1.40-2.99).
CONCLUSION: In this bi-national cohort, overall and multisystem irAE rates were similar, but severe and selected organ-specific toxicities were more frequent in the Swedish population. Geographic and host-related factors may modulate irAE severity and should inform risk-adapted toxicity surveillance.