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

Table 2 Summary of studies providing guidance on mycophenolate mofetil tapering strategies

Study name	Study type	Type of cancer, ICI regimen, and grade of ICI hepatitis at peak LFT elevation	Initial MMF dosing and tapering protocol	Recurrence of ICI hepatitis after MMF taper?	Limitations
Successful mycophenolate mofetil treatment of a patient with severe steroid-refractory hepatitis evoked by nivolumab plus ipilimumab treatment for relapsed bladder cancer[39]	Case report	Bladder cancer. Nivolumab and Ipilimumab combination therapy. Grade 3 ICI Hepatitis	Initial dose: MMF 2 g daily. Taper: MMF tapering started once prednisolone tapered to 10 mg daily. MMF total daily dose was reduced by 0.5 g every 3 days until off	No	Small sample size (n = 1). Patient did not undergo liver biopsy to rule out other causes of liver injury, although serologic and radiographic workup was negative and had good response to treatment of ICI hepatitis
Severe hepatitis arising from ipilimumab administration, following melanoma treatment with nivolumab[55]	Case report	Stage IV melanoma. Nivolumab, followed by ipilimumab (sequential, not combination therapy). Grade 4 ICI hepatitis	Initial dose: MMF 2 g daily. Taper: MMF tapering started once prednisolone tapered to 0.5 mg/kg/d and LFTs improved to Grade 1 hepatitis. MMF initially reduced to 1 g daily, continued for 1 week, then stopped	No	Small sample size (n = 1). Patient did not undergo liver biopsy to rule out other causes of liver injury, although serologic and radiographic workup was negative and had good response to treatment of ICI hepatitis
Immune-mediated liver injury from checkpoint inhibitors: Best practices in 2024[56]	Review article	NA; recommendations provided based upon expert opinion	Initial dose: MMF 500-1500 mg BID. Taper: Begin MMF taper once LFTs normalize. Total daily dose of MMF can be decreased each week by 250-500 mg BID over a span of 6-8 weeks until off	NA; recommendations per expert opinion	Recommendations based upon expert opinion. No specific citations listed relevant to MMF tapering recommendations
Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors[53]	Review article	NA; recommendations provided based upon expert opinion	Initial dose: MMF 1 g BID. Taper: Timing of when to begin taper is not specified. Recommended to taper over 10-12 weeks and can consider resuming ICI once LFTs are normal and both steroids and MMF have been discontinued	NA; recommendations per expert opinion	Recommendations based upon expert opinion. No specific citations listed relevant to MMF tapering recommendation. No recommendation provided on when to begin MMF taper

BID: Twice daily; ICI: Immune checkpoint inhibitor; LFTs: Liver function tests; MMF: Mycophenolate mofetil; NA: Not applicable.