Retreatment With Immune Checkpoint Inhibitors After a Severe Immune-Related Hepatitis: Results From a Prospective Multicenter Study

• Published in: Clinical gastroenterology and hepatology Vol. 21; no. 3; pp. 732 - 740
• Main Authors: Riveiro-Barciela, Mar, Barreira-Díaz, Ana, Callejo-Pérez, Ana, Muñoz-Couselo, Eva, Díaz-Mejía, Nely, Díaz-González, Álvaro, Londoño, María-Carlota, Salcedo, Maria-Teresa, Buti, María
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2023
• Subjects: Antineoplastic Agents, Immunological; Gastroenterology and Hepatology; Hepatitis; Hepatotoxicity; Humans; Immune Checkpoint Inhibitors; Immune-Related Hepatitis; Immunotherapy; Neoplasms - drug therapy; Prospective Studies; Retreatment; Retrospective Studies; LKM1; CTCAE; DILI; RUCAM; ALT; Immune checkpoint inhibitors; ICI; IrAE; ANA; AMA; Immunotherapy; ULN; CTLA-4; PD1; Hepatotoxicity; Immune-Related Hepatitis; drug-induced liver injury; immune checkpoint inhibitor; alanine aminotransferase; liver/kidney microsomal antibody type 1; programmed cell death protein-1; antinuclear antibody; Common Terminology Criteria for Adverse Events; immune-related adverse event; cytotoxic T-lymphocyte-associated antigen; upper limit of normal; antimitochondrial antibody; Roussel Uclaf Causality Assessment Method
• ISSN: 1542-3565; 1542-7714; 1542-7714
• DOI: 10.1016/j.cgh.2022.03.050

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. We present the outcome of a cohort of patients who were retreated with immunotherapy after resolution of severe immune-related hepatitis. We performed a prospective, multicenter, noninterventional 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. Twenty-three 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 (7 and 6 cases, respectively). Immunotherapy was discontinued in all cases. Nineteen patients (82.6%) also received corticoids. Patients mainly were retreated with the same ICI (18 of 23; 78.3%) after a median time of 10 weeks (range, 1–54 wk) 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 of 8 were grade 3 and 3 of 8 were grade 4. Six (75%) had either an underlying autoimmune disease or antinuclear antibodies ≥1/80 (75% vs 26.7%; P = .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 (82.6%) subjects required permanent discontinuation of ICIs, with cancer progression the main reason for discontinuation (9 of 19; 47.8%). Retreatment with 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.