Hepatic immune-related adverse event increased the overall survival of patients with malignancies treated with immune checkpoint inhibitors

Abstract

Background and aim: Associations between the occurrence of abnormal liver function tests, an immune-related adverse event (irAE) caused by immune checkpoint inhibitors (ICIs), and treatment efficacy are unclear. We investigated the association between the incidence of these hepatic irAE occurrences and treatment response in patients treated with ICIs.

Methods: We studied 924 patients treated with ICIs to determine the relationship between the incidence of irAEs and overall survival (OS) with and without the continuation of ICIs due to hepatic irAEs.

Results: Of 924 treated, 338 (36.6%) developed all types of irAEs. Median OS for patients with and without irAEs were 34.3 months (n = 338) and 13.1 months (n = 586), respectively (p = 2.49 × 10^-14). Of 924, 62 (6.7%) patients developed hepatic irAE; 31 discontinued and 31 continued ICI. Of interest, median OS with and without the continuation of ICI therapy due to hepatic irAEs was 54.3 months and 11.5 months, respectively (p = 0.00589). We further compared the difference of liver function tests among the two groups. Although aminotransferases are higher among discontinued group, stigmata of impending hepatic failure were no different among these two groups.

Conclusions: In patients who developed hepatic irAEs, OS was longer in the continued treatment group than in the discontinued treatment group. Most patients who developed hepatic irAEs and stopped the treatment had higher aminotransferase, but often lacks the stigmata of impending hepatic failure such as prothrombin time prolongation or gradual elevation of total bilirubin. Multi-disciplinary cooperation, including hepatologists, may be important for OS improvement by the prolonged use of ICIs.

Keywords: Aminotransferase; Bilirubin; Hepatic failure; Hepatic irAEs; ICI; Malignancy; Multi-disciplinary cooperation; Overall survival; Prothrombin time; irAEs.