We read with considerable interest the manuscript by Jayathilaka et al. [1] regarding the adverse events associated with CTLA-4, PD-1, and PD-L1 inhibitors across various phases of cancer treatment. Endocrine, gastrointestinal, and dermatologic toxicities were the most frequently reported immune-related adverse events (irAEs).Notably, mean event rates for specific irAE types were: cutaneous irAEs, 28.7% (95% CI: 22.9–34.6%); endocrine irAEs, 23.9% (95% CI: 18.8–29.1%); gastrointestinal irAEs, 19.4% (95% CI: 14.1–24.6%); pulmonary irAEs, 18.9% (95% CI: 15.1–22.7%); cardiac irAEs, 18.0% (95% CI: 5.9–30.2%); and renal irAEs, 15.5% (95% CI: 7.3–23.7%). The review reported that combination immune checkpoint inhibitors (ICI) therapies resulted in higher irAE frequencies (mean 45.7%) and severity compared to monotherapies (30.5%), emphasizing the importance of tailored patient management strategies.

We thank the authors for providing this valuable systematic review. We would also like to highlight the importance of oral irAEs as a significant and emerging category of toxicities in patients treated with ICIs. Oral irAEs encompass a range of manifestations, including dry mouth, taste disturbances, and oral mucosal lesions [2,3,4]. These conditions are not only clinically significant but also detrimental to patients’ quality of life, and warrant greater attention in discussions of irAEs. Clinical presentation of oral irAEs poses diagnostic challenges, as their manifestations often resemble other mucocutaneous conditions such as oral lichen planus, erythema multiforme, or Stevens–Johnson syndrome. Accurate differentiation is essential for effective management. Additionally, in a recent report by Xu et al., of patients who experienced oral irAEs, 69% also presented with irAEs in non-oral sites, suggesting a potential relationship between oral and systemic immune dysregulation [5].