Treatment-related adverse events of immune checkpoint inhibitors in clinical trials: a systematic review and meta-analysis.

Aim: This study comprehensively assesses the incidence and profiles of treatment-related adverse events (trAEs) of immune checkpoint inhibitor (ICI)-based therapies across cancer at various sites. Methods: We systematically searched the PubMed, Embase, and Cochrane databases for trials investigating ICI-based therapies published between their inception and August 2023. Results: In total, 147 studies involving 45,855 patients met the inclusion criteria. Among them, patients treated with ICIs reported 39.8% and 14.9% of all-grade and grade ≥3 immune-related adverse events (irAEs), respectively. The most common all-grade irAEs were dermatological and gastrointestinal issues, diarrhea, and pruritus, whereas patients who received ICIs showed most common grade ≥3 irAEs, including gastrointestinal events, diarrhea, increased aspartate aminotransferase and alanine transaminase levels, and hepatic and dermatological events. The overall trAE incidence in patients treated with ICIs was 83.2% for all-grade trAEs and 38.2% for grade ≥3 trAEs. TrAE incidence was highest for patients treated with cytotoxic T lymphocyte antigen-4 inhibitors for all-grade and grade ≥3 trAEs, with incidences of 86.4% and 39.2%, respectively. ICIs combined with targeted therapy showed the highest all-grade and grade ≥3 trAEs, with incidences of 96.3% and 59.4%, respectively. The most common all-grade trAEs were anemia, decrease in white blood cell count, decrease in neutrophil count, nausea, fatigue, diarrhea, and alopecia; patients who received ICIs presented relatively high incidences of grade ≥3 trAEs. Conclusion: This study provided comprehensive data regarding irAEs and trAEs in patients receiving ICIs. These results should be applied in clinical practice to provide an essential reference for safety profiles of ICIs. Systematic review registration: INPLASY platform, identifier INPLASY202380119.