Abstract 511P
Background
Immune checkpoint inhibitor (ICI)-related pneumonitis is a potentially fatal immune-related adverse event (irAE). Hitherto, baseline characteristics associated with ICI-related pneumonitis are still unclear. This study aims to identify distinct phenotypic clusters of ICI-related pneumonitis in an Asian cohort of patients.
Methods
We conducted a retrospective analysis of a pan-cancer cohort comprising 936 patients treated with ICI at the National University Cancer Institute Singapore. Hierarchical clustering of patient baseline characteristics was performed through the complete method of Euclidean distances, with the gap statistic utilized to determine the optimal number of clusters. IrAEs were characterized and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.
Results
936 patients treated with ICI were enrolled. Median age was 63, majority were males (66%), Chinese (74%), ECOG PS ≤1 (86%), stage IV at diagnosis (71%) and non-small cell lung cancer (39%). Pembrolizumab (48%), nivolumab (23%) and durvalumab (12%) were the most commonly prescribed ICIs. Thirty-six patients (4%) developed ICI-related pneumonitis, of which 44% (n=16) were G3 or higher. Hierarchical clustering of baseline patient characteristics identified 2 main distinct Clusters (Cluster 1 n=17, Cluster 2 n=19) of patients with ICI-related pneumonitis. Compared to Cluster 2, onset of ICI-related pneumonitis was more rapid in Cluster 1 (median time to onset 49 days vs 147 days) (log-rank, p=0.13). Cluster 1 had a potentially higher grade of ICI-related pneumonitis (p=0.076), with one patient having G5 pneumonitis. Patients in Cluster 1 were older (69 vs 60, p=0.034), predominantly male (94% vs 79%, p=0.021), had treatment with chemotherapy prior to ICI treatment (77% vs 26%, p=0.023) and had a lower pre-treatment (260×109/L vs 317×109/L, p=0.00075) and 6-week platelet counts (284×109/L vs 355×109/L, p=0.00016).
Conclusions
We identified two distinct Clusters of ICI-related pneumonitis with different baseline characteristics. Future research should focus on identifying various biological mechanisms underpinning ICI-related pneumonitis.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
National Medical Research Council Clinician-Scientist Individual Research Grant New Investigator Grant (MOH-001373-00) and National University Hospital System Seed Fund 2021.
Disclosure
All authors have declared no conflicts of interest.