Abstract 358P
Background
Immune Checkpoint Inhibitors (ICIs) revolutionized advanced non-small cell lung cancer (aNSCLC) treatment, but patients (pts) may experience immune related adverse events (irAEs), impairing quality of life and leading to ICIs discontinuation. Predictor biomarkers of irAEs onset are lacking. Our study explored the baseline circulating immune landscape underlying irAEs onset.
Methods
Detailed data about irAEs were collected in a prospective cohort of aNSCLC pts receiving ICIs (+/− chemotherapy). Circulating immunophenotypes and cytokines levels were assessed at baseline through flow cytometry and multiplex array, and their correlations with irAEs were dissected.
Results
Among 178 pts, 89 (50%) developed irAEs, 36% being high grade (G3-G4) and 22.7% leading to permanent ICIs discontinuation. The most common were gastrointestinal (GI) (44.9%) and cutaneous (41.6%); 37.1% reported multiple irAEs. 31.7% of irAEs occurred within one month from ICI start (early irAEs). Baseline circulating immunophenotype of pts who developed irAEs compared to those who did not, did not show any meaningful difference. Comparing no-irAEs vs high grade irAEs, the latter showed lower IL1b (p=0.01), a trend towards lower soluble PD-L1 (sPDL1) (p=0.08) and higher T cell activation, in terms of CD4+GranzymeB (p=0.009), CD8+GranzymeB (p=0.03), CD4 +Ki67+ (p=0.04), CD8+Perforin (p=0.02). No difference emerged comparing low grade vs no-irAEs. Pts experiencing multiple irAEs, compared to those with a single one, showed lower CD14+PD1MFI (p=0.01) and CD4/CD8 ratio, (p=0.003). Compared to pts without irAEs, pts with multiple irAEs showed lower IL6 (p=0.04), sPDL1 (p=0.02) and CD4/CD8 ratio (p=0.03). Pts with early irAEs revealed higher NK Bright (p=0.01) and CD14+ (p=0.02) compared to irAEs after one month of ICI. Pts with cutaneous irAEs showed higher NK T cells (p=0.01) compared to other irAEs; GI irAEs did not show a peculiar immunophenotypic profile, with an increase both in cytotoxic and regulatory populations.
Conclusions
Our results show that baseline functionally active immune effector phenotypes may identify pts who will develop high grade and multiple irAEs. Cutaneous irAEs harbor a peculiar subset of circulating immune cells when compared to others.
Legal entity responsible for the study
University Hospital of Parma.
Funding
AIRC Associazione Italiana per la Ricerca sul Cancro.
Disclosure
M. Tiseo: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Roche, Amgen, Takeda, MSD, Merck, BMS, Pfizer, Eli Lilly, Novartis, Janssen, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, Roche. All other authors have declared no conflicts of interest.