Abstract 67P
Background
Immune checkpoint inhibitors (ICI) have improved the prognosis of non-small-cell lung cancer (NSCLC) but can also cause immune-related adverse events (irAEs), which can be life-threatening and have a complex management. Currently, there is a need for molecular and clinical markers to predict irAEs occurrence and outcome.
Methods
Clinical characteristics of 762 patients with stage IV NSCLC receiving first- or second-line PD-(L)1 inhibitors were analyzed. Additionally, blood samples of 8 patients with irAEs were analyzed at baseline (BL) and at the time of toxicity (TT) in comparison with 8 matched control samples from patients with similar clinical characteristics and ICI exposure, but no irAEs. The expression of 12 genes involved in the immune response (GATA3, TBX21, MKI67, CD247, FAS, FASLv1, FOXP3, GzmB, IFNγ, PD1, PRF1, RORgt) was absolutely quantified in PAXgene blood RNA samples using RT-PCR and plasmid standards.
Results
IrAEs occurred in 176/762 cases (23%), with a similar frequency for ICI monotherapy or chemoimmunotherapy (24% vs. 22%). CTCAE severity was grade 1 in 11%, grade 2 in 41%, grade 3 in 37%, grade 4 in 10%, and 2 events were lethal (1%). Frequently affected were endocrine glands (21%), lungs (17%), musculoskeletal system (17%), colon (15%) and liver (15%). All other organs were less commonly affected (15%). IrAEs occurrence showed a significant association with a better ECOG performance status (28% vs. 18% for PS 0 vs. 1, p = 0.006), PD-L1 positivity (25% vs. 14%, p = 0.009), and a lower neutrophil-to-lymphocyte ratio (NLR, 28% vs. 19% with the median 6.2 as cut-off, p = 0.004). Blood cell gene expressions in patients with irAEs was slightly higher for 7/12 immunologically relevant genes at TT, and for 11/12 genes at BL, but not significantly different (p≥0.07). No substantial changes in gene expression were noted between BL and TT in each group (mean fold change for the irAEs group = 0.82, for the controls = 0.84, p ≥0.07).
Conclusions
IrAEs under PD-(L)1 inhibitors occur more frequently in patients with PD-L1-positive NSCLC, a better ECOG PS, and a lower NLR. No relationship between the blood expression of selected immunologically relevant genes and irAEs occurrence was noted.
Legal entity responsible for the study
Thoraxklinik Heidelberg.
Funding
German Center for Lung Research (DZL).
Disclosure
P. Christopoulos: Financial Interests, Institutional, Funding, outside the submitted work: AstraZeneca, Amgen, Merck, Novartis, Roche, Takeda; Financial Interests, Personal, Advisory Board, outside the submitted work: Boehringer Ingelheim, Chugai, Pfizer, Roche, AstraZeneca, Daiichi Sankyo, Gilead, Novartis, Takeda; Financial Interests, Institutional, Funding, outside the submitted work.: Boehringer Ingelheim. All other authors have declared no conflicts of interest.