Association between immune checkpoint inhibitor and cytomegalovirus infection: A pharmacovigilance study based on the adverse event reporting system

Abstract Immune checkpoint inhibitor (ICI)‐induced adverse events due to excessive immune stimulation are problematic in immunotherapy. The activation of viral infection triggered by ICI‐induced dysregulated immunity has been proposed; however, this association remains inconsistent. This study investigated the association between ICI administration and cytomegalovirus (CMV) infections, a pathogen linked to immune abnormalities and reactivation, using the Food and Drug Administration Adverse Event Reporting System. We used the crude data set and immunocompromise‐free data set from the fourth quarter of 2012 to 2023. The disproportionality between CMV infection and ICI was analyzed using reporting odds ratio (ROR) and information component (IC) methodologies. Disproportionality between ipilimumab and nivolumab combination case and CMV infection was observed in the crude (ROR: 2.83, 95% confidence interval [CI]: 2.32–3.47; IC: 1.48, 95% CI: 1.14–1.73) and immunocompromise‐free data set (ROR: 1.76, 95% CI: 1.33–2.33; IC: 0.80, 95% CI: 0.33–1.14), whereas disproportionality between other ICI and CMV infection was not observed in the immunocompromise‐free data set. Multiple sensitivity analyses and time‐scan analysis also revealed the consistent disproportionality between ipilimumab and nivolumab combination cases and CMV infection, regardless of the host's immune status. While further research is warranted to validate our findings, these results highlight new insights into ICI‐induced viral infections and suggest the importance of considering the possibility of CMV infections during ipilimumab and nivolumab combination therapy, regardless of the host's immune status.