Relationship between systemic inflammatory response markers and immune treatment related toxicity (IrAEs) in hepatocellular carcinoma (HCC).

Abstract

e16204 Background: A well-recognized class effect of immune check point inhibitors (ICI) is IrAEs ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontinuation of ICI. Treatment related deaths are reported in ̃5% of patients (pts) treated with ICI. There are, however, no reliable markers to predict the onset & severity of IrAEs. We tested the association between neutrophil-lymphocyte ratio (NLR) & platelet-lymphocyte ratio (PLR) at baseline with development of clinically significant IrAE (graded ≥2) in HCC pts treated with ICI. Methods: Data was extracted from a large international database from a consortium of 11 tertiary-care referral centers located in the USA, Europe & Asia. NLR=Absolute neutrophil count/ Absolute lymphocyte count (ALC) & PLR=Platelet count/ALC. A cutoff of 5 for was used NLR & 300 for PLR based on literature. We also tested the association between antibiotic & steroid exposure to IrAEs. Results: Clinical data was collected from 361 pts treated between 2016–2020 across the USA (66%), Asia (12%) & Europe (22%) in this multinational database. Most pts received Nivolumab monotherapy (n=318, 74%). 167 (46%) pts developed at least one IrAE, highest grade 1 in 80 (48%), grade ≥2 in 87(52%) pts. Baseline characteristics did not differ significantly between the groups (Table). In a univariable regression model to predict grade ≥2 IrAEs, a PLR >300 was associated with a lower incidence of clinically significant IrAEs (OR = 0.40; p=0.044). NLR >5 was associated with a trend toward lower incidence of clinically significant IrAEs (OR = 0.58; p=0.097). Multivariate analyses confirmed PLR as independent predictive marker of grade ≥2 IrAEs (OR = 0.24; p=0.007). Antibiotics use was not associated with IrAE incidence (OR = 1.02; p=0.954). Steroid use was associated with a >2-fold higher incidence of grade ≥2 IrAEs (OR = 2.74; p<0.001), though it may be noted that 37% of pts received steroids for treatment of IrAEs. Conclusions: Lower NLR & PLR may predict the appearance of IrAEs in HCC treated with ICI, although this conclusion warrants prospective validation. This finding is in keeping with several studies that showed improved survival in pts who develop of IrAEs & have a lower NLR & PLR.[Table: see text]