Abstract
BACKGROUND: Immune-related hepatitis (ir-hepatitis) is an immune-related adverse event that can be resistant to systemic steroid therapy. Mycophenolate mofetil (MMF) is recommended for steroid-refractory cases; however, evidence supporting its efficacy remains unclear. We aimed to evaluate the efficacy of MMF in patients with solid tumors, the optimal timing for administration, and its effect on cumulative steroid dosage. METHODS: A retrospective cohort analysis was conducted between January 2015 and August 2023. We obtained data from eligible consecutive patients who developed ir-hepatitis with grade ≥ 2 alanine aminotransferase (ALT) elevation requiring systemic steroids. Participants were divided into three groups: MMF-early combination, MMF-late combination, and systemic steroid-only. ALT improvement rate was used to assess the efficacy of MMF based on the Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Among 4405 patients treated with immune checkpoint inhibitors, 151 (3.4%) developed ir-hepatitis requiring systemic steroids, of whom 123 had grade ≥ 2 ALT elevation. The median patient age was 62 years (interquartile range: 54-72), and 42 patients (34%) received MMF. Forty-one patients were evaluable for MMF timing. The ALT improvement rate on day 7 was significantly higher in the MMF-early combination group (n = 10) than in the MMF-late combination group (n = 31) (78.5% vs. 41.6%, p < 0.01). Among 40 patients evaluable for steroid dosage, cumulative systemic steroid dosage was significantly lower in the MMF-early combination group (n = 8) than in the MMF-late combination group (n = 32) (2121 mg vs. 3745 mg, p = 0.03). These effects were comparable even for the MMF-early combination and systemic steroid-only groups. CONCLUSIONS: Despite the small sample size, early combination therapy with MMF and systemic steroids rapidly improved ir-hepatitis, consequently reducing the cumulative systemic steroid dosage.