Lessons from Pharmacovigilance: Pulmonary Immune-Related Adverse Events After Immune Checkpoint Inhibitor Therapy

Abstract

Purpose To characterize pulmonary toxicities associated with the use of novel immune checkpoint inhibitors Methods Adverse event reports from immune checkpoint inhibitors targeting PD-1/L1 and CTLA-4 were captured from the W.H.O pharmacovigilance database (VigiBase) up until Dec. 31st 2019 and were analyzed to evaluate for measures of association between the use of immune checkpoint inhibitors and pulmonary toxicities. Disproportionality analysis using both frequentist and Bayesian approaches were used to detect signals between pulmonary immune-related adverse events and the use of these agents. Results A total of 9202 adverse pulmonary immune checkpoint inhibitor-related events were captured up until 2019. Adverse pulmonary events were compromised of 1305 airway, 18 alveolar, 5491 interstitial, 898 pleural, 560 vascular and 939 non-specific pulmonary events. We found a common association between all immune checkpoint inhibitors studied and pneumonitis, interstitial lung disease, pulmonary embolism and respiratory failure. We also noted other associations between immune checkpoint inhibitors, however not as uniformly across agents. Most of these immune-related adverse drug reactions were noted to be severe and accounted for a significant source of mortality in the reported cases. Conclusion Immune checkpoint inhibitors are associated with a spectrum of inflammatory pulmonary toxicities. The breadth of pulmonary complications and prevalence may be underappreciated with the use of these agents.