Risk factors and outcomes for steroid-refractory immune-related hepatotoxicity in locally advanced and metastatic cancer.

Abstract

e24162 Background: Immune-related hepatotoxicity (IRH) is one of the common immune-related adverse events caused by immune checkpoint inhibitors (ICIs). Some patients with steroid-refractory IRH (Ref-IRH) are potentially life-threatening. This study was designed to determine the risk factors and outcomes for Ref-IRH. Methods: Advanced or metastatic cancer patients who developed steroid-responsive IRH (Res-IRH) or Ref-IRH were identified between 1 December 2019 and 1 September 2024. Patient characteristics, peripheral blood biomarkers, and cytokine levels were collected. Results: In this cohort of 480 patients treated with immune checkpoint inhibitors, 35 patients (7.3%) developed IRH, including 12 with Res-IRH and 13 with Ref-IRH. Patients with Ref-IRH were more likely to be hepatocellular carcinoma (p=0.035), receive ICIs plus targeted therapy (p=0.046), and have higher CTCAE grades (p=0.044) at diagnosis. Patients with Ref-IRH had lower platelet counts (p=0.006), higher procalcitonin levels (p=0.012), and higher IL-6 levels (p=0.038). Multivariate logistic regression analysis indicated that higher IL-6 at diagnosis was an independent risk factor for Ref-IRH (p=0.031). All Ref-IRH patients were treated with immunosuppressive agents. The survival outcomes of Ref-IRH were comparable to those of Res-IRH. Patients with Ref-IRH were unlikely to quickly recover with a longer time from initial diagnosis of IRH to resolution to grade 1 (p=0.002), from peak ALT (p=0.007), AST (p=0.011), and TBIL (p=0.048) to resolution to grade 1, from initial diagnosis of IRH to use of prednisone ≤20 mg/day (p=0.025), and prolonged hospital length of stay (p=0.017). Among 14 patients who underwent liver biopsy, 3 were diagnosed with vanishing bile duct syndrome (VBDS) and 11 with non-VBDS. The survival outcomes of VBDS were comparable to those of non-VBDS, but patients with VBDS had lower 8-week, 10-week, and 12-week improvement rates compared with non-VBDS patients (p=0.011, p=0.011, p=0.033, respectively). Conclusions: High IL-6 at diagnosis is an independent risk for developing Ref-IRH. There was no significant difference in efficacy and survival between patients with Ref-IRH and Res-IRH, patients with VBDS and non-VBDS, but much more time from the initial diagnosis of IRH to resolution to grade 1 and the use of immunosuppressive agents is needed for Ref-IRH patients.