Systematic review and meta-analysis of RCTs of the impact of ICIs on infection risk in patients with solid malignancies

Immune checkpoint inhibitors (ICIs) revolutionized cancer treatment but may increase infection risk. A systematic review and meta-analysis by researchers at Fujian Medical University (Fuzhou, China) assessed infection risk associated with ICI use for solid cancers in randomized controlled trials (RCTs) published through October 10, 2025. The primary endpoint was risk ratio (RR) of all-grade infections and the secondary endpoint was the RR of severe (grade 3-5) infections. A total of 141 RCTs (84,484 participants) were included. In treatment-emergent adverse events (TEAEs)-based analyses, ICIs were associated with increased risks of any-grade infections (RR 1.25; 95% CI 1.12-1.39; I²=71.1%) and severe infections (1.30; 1.17-1.44) drive by symmetric comparisons (ICI versus placebo and ICI plus chemotherapy versus chemotherapy). In treatment-related adverse events (TRAEs)-based analyses, no significant increase was seen for any-grade infections (RR 1.01; 95% CI 0.84-1.22; I²=67.3%) or severe infections (0.96; 0.81-1.14). However, symmetric comparisons again showed increased TRAE risks for ICI versus placebo and ICI plus chemotherapy versus chemotherapy. Publication bias was suggested for any-grade infectious TRAEs. The authors conclude that the relationship between ICI therapy and infection risk is nuanced and context-dependent. In symmetric comparisons, ICIs are associated with modestly increased TEAE- and TRAE-based infection risks. This risk should be weighted against the expected survival benefit, underscoring the need for individualized asssessment.