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Background & Aims

Liver injury related to immunotherapy is a relatively frequent immune-related adverse event that requires permanent discontinuation of checkpoint inhibitors (CPIs) in severe cases. We present the outcome of a cohort of patients who were retreated with immunotherapy after resolution of severe immune-related hepatitis.

Patients and Methods

A prospective, multicenter, non-interventional study that included all consecutive patients with cancer and previous grade 3 or 4 immune-related hepatitis who were retreated with CPIs in three academic hospitals.

Results

Twenty-three patients who developed severe immune-related hepatitis were included: 20/23 (87.0%) received a single CPI and 3/23 (13.0%) received anti-PD-1 plus anti-CTLA-4. The most frequent cancers were lung cell and urinary tract (7 and 6 cases, respectively). Immunotherapy was discontinued in all cases. Nineteen (82.6%) also received steroids. Patients were mainly retreated with the same CPI (18/23, 78.3%) after a median time of 10 weeks (range 1-54) from the severe immune-related hepatitis. Fifteen patients (65.2%) did not have recurrence of the immune-related hepatitis after retreatment. Among the 8 (34.8%) subjects with recurrence, 5/8 were grade 3 and 3/8 were grade 4. Six (75%) had either an underlying autoimmune disease or antinuclear antibodies (ANAs) ≥1/80 (75% vs 26.7%, P=0.037). None of the patients with previously grade 4 hepatitis recurred, and those patients who recurred tended to present better oncological prognosis. Overall, 19 (82.6%) subjects required permanent discontinuation of CPIs, with cancer progression as the main reason for discontinuation (9/19, 47.8%).

Conclusions

Retreatment with CPIs is a feasible option after a severe immune-related hepatitis, even with the same CPIs, without recurrence of the liver injury retreatment in up to 65% of patients.

You can read an interview with the lead study author here, and about the clinical implications of the study here.