1071P - Analysis of pulmonary adverse events associated with immune checkpoint inhibitors based on FAERS and VigiBase database

Background

The utilization of immune checkpoint inhibitors (ICIs) has become increasingly prevalent in cancer treatment. However, ICIs may also precipitate a spectrum of immune-related adverse events, which can target various organ systems. Among these, pulmonary immune-related adverse events (pirAEs) are the leading cause of ICI cessation and mortality.

Methods

Individual Case Safety Reports (ICSRs) were obtained from FAERS and VigiBase. We identified reports pertaining to eight ICIs for the purposes of this study, namely nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, durvalumab, ipilimumab, and tremelimumab. Subsequently, we utilized expert consensus to select 52 significant pirAEs with high incidence or of clinical significance and then evaluated the incidence and mortality of pirAEs across varying time periods following the initiation of ICIs therapy.

Results

16,372 and 7,943 ICSRs were collected using FAERS and VigiBase, respectively. More than 50% of pirAEs occurred within 60 days after treatment with ICIs (FAERS:70.0%,VigiBase:55.7%), and their mortality was higher than that after 60 days (15% vs 12%, 12% vs 7%). In each period after the use of ICIs, pirAEs with the highest incidence were interstitial lung disease (14.6%,26.4%), dyspnoea (18.4%,17.0%)and pneumonitis (13.0%,17.0%). The all-cause mortality of respiratory failure (30%, 58%), pulmonary hemorrhage (28%,57%), acute interstitial pneumonitis (75%, 27%), and stridor (31%, 30%)was over 25%. The mortality of respiratory failure remained stable at a high level in each period after initiation of immune therapy (24-40%, 42-69%).

Conclusions

Using data from the FAERS and VigiBase, we conducted an analysis of the frequency and incidence of pirAEs during varied periods after the onset of ICIs therapy. We offer a groundbreaking revelation, identifying the occurrence of pirAEs which manifest early on, within the initial 60 days of treatment, and exhibit a high incidence and mortality rate. Among pirAEs, interstitial lung disease, dyspnea, and pneumonitis were most frequently reported with respiratory failure being a consistently fatal adverse event highlighting the necessity of heightened physician vigilance.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.