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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Balancing act: Tapering mycophenolate mofetil in immune checkpoint inhibitor hepatitis-strategies, outcomes, and risks
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
Sahaj Mujumdar, Sofia Shaikh, Anuroop Yekula, Daniel R Weinberg, Sarah B McPherson, Mark Levstik, Patrick Twohig, Department of Gastroenterology and Hepatology, University of Rochester Medical Center, Rochester, NY 14682, United States
Shu-Yen Chan, Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232
Nida S Ansari, Internal Medicine, St. Joseph’s University Medical Center, Paterson, NJ 07504, United States
David Jerez Diaz, Internal Medicine, Florida State University, Sarasota Memorial Hospital, Sarasota, FL 34239, United States
Andrew M Moon, Department of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, NC 27713, United States
Author contributions: Mujumdar S, Shaikh SD, Yekula A, Weinberg DR, McPherson SB, Chen SY, Ansari NS, Jerez Diaz D, Levstik M, Moon AM, and Twohig P contributed equally to this work; Twohig P designed the overall concept and outline of the manuscript Mujumdar S, Shaikh SD, Yekula A, Weinberg DR, McPherson SB, Chen SY, Ansari NS, and Jerez Diaz D conducted the literature review and drafted the manuscript; Mujumdar S, Levstik M, Moon AM, and Twohig P made critical revisions; all authors prepared the draft and approved the submitted version.
Conflict-of-interest statement: Andrew M Moon is a consultant for TARGET RWE, Intercept Pharmaceuticals, IDEOlogy, Eisai, and Astra Zeneca, and receives research funding from the AASLD, ACG, NIH, Madrigal and DCN Diagnostic. All other authors report no conflicts of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Patrick Twohig, MD, Assistant Professor, FRCPC, Department of Gastroenterology and Hepatology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14682, United States.
patrick_twohig@urmc.rochester.edu
Received: May 13, 2025
Revised: June 7, 2025
Accepted: September 2, 2025
Published online: December 5, 2025
Processing time: 206 Days and 23.2 Hours
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
There was significant heterogeneity in the duration of MMF taper, which ranged from 4 weeks to greater than 6 months. The tapering schedules presented were individualized based on the severity of liver injury, patient response to treatment, and risk factors for relapse. We summarize current tapering approaches, including rapid vs 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.
Core Tip: This systematic review describes immune checkpoint inhibitor hepatitis (ICI) hepatitis and explores the different treatment strategies for this condition, with a focus on the data behind one of the second line agents used for treatment, mycophenolate mofetil (MMF). We review the evidence behind use of MMF for ICI hepatitis, including pathophysiology, clinical outcomes, risk of relapse, tapering strategies, and challenges with restarting immunotherapy in these patients. Future directions and unmet needs within this evolving field are also briefly discussed.
