The impact of immune checkpoint inhibitors on infection in patients with solid malignancies: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Immune checkpoint inhibitors (ICIs) revolutionised cancer treatment but may alter infection risk. The effect of ICIs on infection susceptibility remains unclear. METHODS: We searched PubMed, the Cochrane Library, and EMBASE from database inception to October 10, 2025 for randomised controlled trials (RCTs). The primary endpoint was the risk ratio (RR) of all-grade infections; the secondary endpoint was the RR of severe (Grade 3-5) infections. Stratified analyses by ICI agent, regimen, treatment timing, infection site, and cancer type were performed separately for treatment-emergent adverse events (TEAEs) and treatment-related adverse events (TRAEs). Publication bias was assessed using funnel plots, Egger's test, and trim-and-fill; heterogeneity was evaluated by I 2 statistic. This study is registered with PROSPERO, number CRD420251231682. FINDINGS: A total of 141 RCTs (87,484 participants) were included. In TEAE-based analyses, ICIs were associated with increased risks of any-grade infections [RR = 1.25; 95% confidence interval (CI): 1.12-1.39; I 2 = 71.1%] and severe infections (RR = 1.30; 95% CI: 1.17-1.44), driven by symmetric comparisons (ICI vs. Placebo and ICI plus chemotherapy vs. chemotherapy). For TRAEs, no significant increase was seen for any-grade infections (RR = 1.01; 95% CI: 0.84-1.22; I 2 = 67.3%) or severe infections (RR = 0.96; 95% CI: 0.81-1.14). However, symmetric comparisons again showed increased TRAE risks for ICI vs. placebo and ICI plus chemotherapy vs. chemotherapy. Publication bias was suggested for any-grade infectious TRAEs (Egger's P = 0.015); after trim-and-fill correction, the pooled RR was strengthened (RR = 1.24). INTERPRETATION: 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 weighed against the expected survival benefit, underscoring the need for individualised assessment. Future prospective studies with time-to-event analyses and standardised infection surveillance are needed to clarify the temporal relationship between ICI exposure and infection risk. FUNDING: There was no funding source for this study.