Liver and Bile

Clin Gastroenterol Hepatol. 2023;21(3):732–40

Riveiro-Barciela M, Barreira-Díaz A, Callejo-Pérez A, Muñoz-Couselo E, Díaz-Mejía N, Díaz-González Á, Londoño MC, Salcedo MT, Buti M

Retreatment with immune checkpoint inhibitors after a severe immune-related hepatitis: Results from a prospective multicenter study

Background and aims: Liver injury related to immunotherapy is a relatively frequent immune-related adverse event that requires permanent discontinuation of immune checkpoint inhibitors (ICIs) in severe cases. The authors present the outcome of a cohort of patients who were retreated with immunotherapy after resolution of severe immune-related hepatitis.
Methods: They performed 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 ICIs in 3 academic hospitals.
Results: 23 patients who developed severe immune-related hepatitis were included: 20 of 23 (87.0%) received a single ICI and 3 of 23 (13.0%) received anti-programmed cell death protein-1 plus an anti-cytotoxic T-lymphocyte-associated antigen. The most frequent cancers were lung cell and urinary tract cancers (7 and 6 cases, respectively). Immunotherapy was discontinued in all cases. 19 patients (82.6%) also received corticoids. Patients mainly were retreated with the same ICI (18/23; 78.3%) after a median time of 10 weeks (range, 1–54 weeks) from the severe immune-related hepatitis. 15 patients (65.2%) did not have recurrence of the immune-related hepatitis after retreatment. Among the 8 subjects (34.8%) with recurrence, 5 of 8 were grade 3 and 3 of 8 were grade 4. Six (75%) had either an underlying autoimmune disease or anti-nuclear antibodies ≥ 1/80 (75% vs. 26.7%; p = 0.037). None of the patients with previously grade 4 hepatitis had a recurrence, and those patients who had a recurrence tended to present with a better oncological prognosis. Overall, 19 subjects (82.6%) required permanent discontinuation of ICIs, with cancer progression as the main reason for discontinuation (9/19; 47.8%).

Conclusions: Retreatment with immune checkpoint inhibitors (ICIs) is a feasible option after a severe immune-related hepatitis, even with the same ICIs, without recurrence of the liver injury retreatment in up to 65% of patients.

Prof. Dr. M. Riveiro-Barciela, Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d’Hebron, Barcelona, Spain,

DOI: DOI: 10.1016/j.cgh.2022.03.050

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