Pre-treatment predictors of immune-mediated hepatitis in non-small cell lung cancer patients treated with immune-checkpoint inhibitors: A retrospective study.

Abstract

e15136 Background: Immune-checkpoint inhibitors (ICIs) have become standard of care for patients with non-oncogenic driven metastatic non-small cell lung cancer (NSCLC); a feat that has dramatically changed prognosis for these patients. Nevertheless, ICIs can cause immune-related adverse events (irAEs) requiring steroid administration or treatment cessation. This cohort study aimed to examine the incidence of ICI related hepatitis and determine potential predictors of immune-mediated hepatitis. Methods: We retrospectively collected clinicopathological data from 139 patients with metastatic NSCLC treated at Westmead and Blacktown Public Hospitals between 2017 and 2019. Blood tests results were collected longitudinally with a particular focus on liver function tests (LFTs). Further, parameters associated with acute or chronic liver hepatitis were statistically analyzed regarding their association with toxic elevation of LFTs. In particular we were interested in body weight, liver fibrosis (measured by AST to Platelet Ratio Index [APRI] and Fib-4 score), AST/ALT ratio, albumin, globulin, direct/indirect bilirubin, gamma-glutamyl transferase, ratio of serum protein (SP) to total bilirubin (TB) and C-reactive protein. Results: ICIs were more effective in terms of overall (p = 0.0001) and progression-free (p = 0.007) survivals compared to chemotherapy. Pre-treatment blood tests revealed no abnormalities in LFTs, however, at week 9 we first detected elevated LFTs in 29% (n = 18) and 6.5% (n = 5) of ICI and chemotherapy groups, respectively (p = 0.0003). Multivariate regression found that abnormal transaminases at week 9 significantly correlated with high pre-treatment ratio of SP/TB (p = 0.001) in the ICI group only. Specifically, a pre-treatment SP/TB ratio of was > 5 associated with increased ALT at week 9 (odds ratio 92%; positive and negative predictive values: 74% and 97% respectively; sensitivity 94%; specificity 86%). Interestingly, no other significant correlations with elevated transaminases at week 9 were established. Conclusions: In this real-world cohort, we confirmed that ICI therapy results in improved PFS and OS comparing to chemotherapy alone. Moreover, a pre-treatment ratio of SP/TB > 5 was significantly associated with elevated LFTs at week 9 suggesting that it may have a predictive role.