Clinical Outcomes of Gradual Corticosteroid Tapering for Immune Checkpoint Inhibitor‐Induced Liver Injury
Naoto Soma, Yoshihito Uchida, Kayoko Sugawara, Masamitsu Nakao, Nobuaki Nakayama, Yukinori Imai, Suguru Mizuno, Satoshi MochidaABSTRACT
Background and Aim
Immune checkpoint inhibitor (ICI)‐induced liver injury is a clinically important adverse event that may lead to interruption of anticancer therapy. Although systemic corticosteroids are recommended for severe cases, the optimal corticosteroid tapering strategy for relapse prevention and subsequent ICI rechallenge has not been established. We evaluated the clinical outcomes of an empirical institutional gradual corticosteroid tapering strategy developed with reference to Japanese AIH management.
Methods
We retrospectively analyzed 36 consecutive patients with grade ≥ 3 ICI‐induced liver injury. Prednisolone (PSL) was generally initiated at 0.8 mg/kg/day and tapered gradually at a rate of 5 mg every 2 weeks. Steroid pulse therapy was selectively administered in patients with severe liver injury with signs of liver failure. The primary endpoint was relapse during corticosteroid tapering.
Results
Liver injury improved in 35 of 36 patients (97%). The median duration required to taper PSL to ≤ 10 mg/day was 73 (range, 50–168) days. Relapse during corticosteroid tapering occurred in only 1 patient (3%), and no patients required additional immunosuppressive therapy, including mycophenolate mofetil. ICI rechallenge was performed in 13 patients, including 6 with prior CTCAE grade 4 liver injury, and recurrence after rechallenge occurred in only 1 patient (8%). Histopathological findings were characterized predominantly by lobular inflammation with CD8‐positive T‐cell infiltration, whereas classical autoimmune hepatitis‐associated features were relatively limited.
Conclusions
An empirical gradual corticosteroid tapering strategy developed with reference to Japanese AIH management may contribute to relapse prevention and facilitate ICI rechallenge in patients with ICI‐induced liver injury.