Balancing act: Tapering mycophenolate mofetil in immune checkpoint inhibitor hepatitis-strategies, outcomes, and risks
Year: 2025
Type: article
Study design: Systematic Review
Abstract: 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.
Authors: Sahaj Mujumdar, Sofia Shaikh, Shu-Yen Chan, Anuroop Yekula, Daniel R Weinberg, Nida S Ansari, David Jerez Diaz, Sarah B McPherson, Mark Levstik, Andrew M Moon, Patrick Twohig
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
Funders: U.S. Department of Veterans Affairs, Bill and Melinda Gates Foundation, Cancer Prevention and Research Institute of Texas, Bernard van Leer Foundation, Takeda Science Foundation, Jinan Science and Technology Bureau, Uehara Memorial Foundation, Iowa State University, Wellcome Trust, University of Manitoba, Experimental Psychology Society, Cecil and Irene Hylton Foundation, Asia Pacific University of Technology and Innovation, Leverhulme Trust, European Commission, Deutsche Forschungsgemeinschaft, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, National Natural Science Foundation of China, Aalto-Yliopisto, Adolphe Merkle Foundation, Fudan University, Indian Institute of Technology Roorkee, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Mitacs, China Scholarship Council, Ministerio de Ciencia y Tecnología, Addis Ababa University, Global Affairs Canada, National Institutes of Health, Iowa Department of Natural Resources, Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Japan Society for the Promotion of Science, Science and Engineering Research Board, National Center of Competence in Research Bio-Inspired Materials, University of Fribourg, H2020 European Research Council, HORIZON EUROPE European Innovation Council
OpenAlex ID: W4417021548