Co-Occurring Infections in Cancer Patients Treated with Checkpoint Inhibitors Significantly Increase the Risk of Immune-Related Adverse Events

Simple Summary This study analyzed over eighty thousand adverse event reports from the Food and Drug Administration's Adverse Event Reporting System to identify records of patients administered with immune checkpoint inhibitors as monotherapy for various malignancies. We analyzed whether co-occurring viral, bacterial, or fungal infections increased the risk of developing immune-related adverse events, such as pneumonitis, sarcoidosis, myocarditis, nephritis, colitis, hepatitis, and others, in cancer patients treated with those inhibitors and quantified the association. We have found a statistically significant, at the 95% confidence level, association between co-occurring infections and immune-related adverse events in cancer patients treated with immune checkpoint inhibitors.Abstract Therapeutic antibodies designed to target three immune checkpoint proteins have been applied in the treatment of various malignancies, including small and non-small cell lung cancers, melanoma, renal cell carcinoma, and others. These treatments combat cancers by reactivating cytotoxic T cells. Nevertheless, this mode of action was found to be associated with a broad range of immune-related adverse events (irAEs), including pneumonitis, sarcoidosis, myocarditis, nephritis, colitis, and hepatitis. Depending on their severity, these irAEs often necessitate the suspension or discontinuation of treatment and, in rare instances, may lead to fatalities. We analyzed over nineteen million reports and identified over eighty thousand adverse event reports from patients treated with immune checkpoint inhibitors submitted to the Food and Drug Administration's Adverse Event Reporting System MedWatch. Reports concerning pembrolizumab, nivolumab, cemiplimab, avelumab, durvalumab, atezolizumab, and ipilimumab revealed a statistically significant association between the irAEs and concurrent infectious diseases for five out of seven treatments. Furthermore, the association trend was preserved across all three types of checkpoint inhibitors and each of the five individual therapeutic agent cohorts, while the remaining two showed the same trend, but an increased confidence interval, due to an insufficient number of records.