Balancing act: Tapering mycophenolate mofetil in immune checkpoint inhibitor hepatitis-strategies, outcomes, and risks

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but are associated with immune-related adverse events, including ICIs hepatitis. Mycophenolate mofetil (MMF) is often used as a second-line immunosuppressive agent for steroid-refractory cases. However, there is no standardized approach to MMF tapering, leading to uncertainties regarding relapse risk, optimal tapering strategies, and long-term outcomes. AIM: To evaluate current evidence on MMF tapering in ICI hepatitis, focusing on strategies, clinical outcomes, and the risk of hepatitis recurrence. Additionally, we explore the feasibility of reintroducing ICI therapy after immunosuppression withdrawal. METHODS: A comprehensive literature search was conducted in PubMed, EMBASE, and clinical trial registries to identify studies reporting MMF use and tapering strategies in ICI hepatitis. We extracted data from manuscripts including patient characteristics, MMF dosing regimens, tapering duration, relapse rates, and oncologic outcomes. Risk factors for recurrence and successful tapering were analyzed. RESULTS: slow withdrawal, predictors of successful tapering, and alternative immunosuppressive strategies. The impact of MMF duration on liver recovery, relapse risk, and cancer prognosis will be discussed. Evidence on ICI rechallenge post-taper will also be reviewed. CONCLUSION: While MMF is effective in managing ICI hepatitis, tapering remains a clinical challenge with potential risks of hepatitis flare and disease progression. Standardized tapering protocols are needed to optimize immunosuppression while preserving anticancer efficacy. Future studies should focus on biomarker-driven tapering strategies and prospective trials to establish best practices.