The discovery of immune checkpoint inhibitors (ICIs), which include anti-programmed cell death protein-1 (PD-1), its ligand (PD-L1) and anti-cytotoxic T cell lymphocyte-associated protein-4 (CTLA-4), has transformed the field of oncology, with indications continuing to increase. For example, anti-PD1 and anti-CTLA-4 ICIs, which include nivolumab, pembrolizumab and ipilimumab, are US Food and Drug Administration/European Medicines Agency approved for a variety of cancers, such as melanoma and non-small cell lung carcinoma (NSCLC) [1]. Considered the Achilles' heel of ICIs, however, are immune-related adverse events (irAEs) (10-60% high grade) that represent an inflammatory response that can affect multiple organ systems, which can be fatal (0.3-1.3%) [2]. Among these irAEs is ICI-related pneumonitis, which is a serious adverse event with reports of up to 1% to 4% of patients on ICI monotherapy and 4% to 7% on combination therapy [3,4]. Most of the available data were derived from clinical trials that may not be representative of a real-world population and settings. As such, reports of ICI-pneumonitis in the international pharmacovigilance database, Vigibase, were retrospectively reviewed to characterise their main features and factors associated with death.Our study is a descriptive analysis based on adverse drug reactions (ADR) reported within VigiBase, the World Health Organization global deduplicated individual case safety reports (ICSRs) database, originating from more than 130 countries [5][6][7]. VigiBase contains over 18 million ICSRs submitted by national pharmacovigilance centres since 1967. These reports mainly originate from real-life populations with different sources, including healthcare professionals, patients and pharmaceutical companies. The use of confidential electronically processed patient data was approved by the French National Commission for Data Protection and Liberties (reference: 1922081). This study is part of NCT03492242 [5][6][7].We performed a search for ADRs associated with anti-CTLA-4, anti-PD1, anti-PD-L1, and their combinations. We searched all ICI-pneumonitis according to the Medical Dictionary for Drug Regulatory Activities (MedDRA) using the preferred term "pneumonitis", up to 4 November, 2018. ICI-pneumonitis specifically considered in the analysis were those reported as "suspected" secondary to ICI. Demographic and clinical data were collected and reviewed. Characteristics of cases were described in terms of mean±SD or medians (with interquartile ranges (IQR)) for quantitative variables, and in terms of effective and proportion for qualitative ones. To compare fatal versus non-fatal pneumonitis, unpaired t-test, Mann-Whitney and χ 2 -tests were calculated, as appropriate (R-software).Between inception through November 04, 2018, a total of 1694 ICI-pneumonitis were identified with a marked increase in reporting of ICI-pneumonitis of approximately 4 cases per month between 2010 and 2014 to 71 cases per month in 2018. The majority of cases originated from North America (47.5%)...
