Mycophenolate mofetil for immune checkpoint inhibitor-related hepatotoxicity relapsing during dose reduction of corticosteroid: A report of two cases and literature review.

BACKGROUND: Immune checkpoint inhibitors (ICIs) sometimes cause immune-related liver injury, which can lead to cessation of treatment, hospitalization, and even mortality. Although high-dose corticosteroids are usually effective in treatment of ICI-related liver injury, one fifth of affected patients require additional immunosuppressive therapy. It remains uncertain how best to treat ICI-related liver injury that relapses under corticosteroid therapy after temporary remission.

CASE: Here we report two cases of ICI-related liver injury successfully treated with mycophenolate mofetil (MMF). In the first case, a 74-year-old man with stage IIIA lung cancer underwent curative chemoradiotherapy. After the second infusion of durvalumab, grade 3 ICI-related liver injury (mixed pattern) developed. In the second case, a 46-year-old man with stage IVB lung cancer received pembrolizumab-containing chemotherapy. After the first cycle, grade 2 ICI-related hepatitis developed. In the both cases, liver injury improved with high-dose prednisolone but relapsed during tapering of the drug. After liver biopsy was performed to confirm the diagnosis of ICI-related liver injury, MMF (2000 mg/day) was added. MMF was effective for both patients and permitted discontinuation or reduction of prednisolone.

CONCLUSION: MMF appears to be an appropriate treatment option for ICI-related liver injury that respond to high-dose corticosteroids but relapse during steroid tapering.