S5898 A Case of Steroid-Refractory Immune Checkpoint Inhibitor Hepatitis Successfully Treated With Mycophenolate Mofetil

Introduction: Immune checkpoint inhibitors (ICI) have revolutionized cancer therapy, however they are associated with immune-related adverse events, including ICI hepatitis. While corticosteroids are first-line treatment, steroid-refractory cases pose a therapeutic challenge, with limited data guiding second-line immunosuppressive management. We describe a case of steroid-refractory grade 4 ICI hepatitis that responded successfully to mycophenolate mofetil (MMF). Case Description/Methods: A 36-year-old woman with metastatic melanoma presented with asymptomatic hepatocellular injury (alanine aminotransferase [ALT] 346 U/L, aspartate aminotransferase [AST] 194 U/L) 6 weeks after her third cycle of nivolumab and ipilimumab. Despite ICI discontinuation and 2 weeks of oral prednisone at 1–1.5 mg/kg, her transaminases worsened. Her only medications included long-term bupropion 300 mg daily and magnesium supplementation. Serologic testing for all viral and autoimmune etiologies was negative. She was hospitalized and treated with intravenous pulse-dose steroids for 3 days, but her transaminases remained significantly elevated with peak ALT 1417 U/L and AST 327 U/L. Liver biopsy revealed CD8+ T-cell predominant infiltration, consistent with ICI-induced hepatocellular injury. MMF was initiated at 1 g BID, but was soon escalated to 1.5 g BID. Over the subsequent 8 weeks, liver enzymes normalized and MMF was tapered over 5 weeks with a concurrent prednisone taper. There was sustained improvement in liver function without rebound elevation while off of immunosuppression. Her melanoma is currently under surveillance, with ongoing discussions regarding restarting immunotherapy. Discussion: ICI hepatitis generally arises within 8 to 12 weeks of therapy and is driven by CD8+ T-cell-mediated hepatocellular injury. Evidence for second-line immunosuppressants is limited. Current clinical practice is largely based on case reports with minimal information on dosing and duration of these agents. This case supports the use of high-dose MMF as an effective second-line immunosuppressive agent in ICI hepatitis. It also highlights that prolonged high-dose steroid therapy was ineffective at markedly elevated liver enzyme levels, and earlier initiation of second-line therapy could have been beneficial. These patients may require prolonged immunosuppression to prevent rebound hepatitis and manage other immune toxicities. Reintroducing immunotherapy after ICI hepatitis also remains a challenge and must be individualized.