Characteristics and outcomes of immunotherapy-related liver injury in patients with hepatocellular carcinoma versus other advanced solid tumours

  • Ciro Celsa (Shared first author)
  • Giuseppe Cabibbo (Shared first author)
  • Claudia Am Fulgenzi
  • Bernhard Scheiner
  • Antonio d'Alessio
  • Giulia F Manfredi
  • Naoshi Nishida
  • Celina Ang
  • Thomas U Marron
  • Anwaar Saeed
  • Brooke Wietharn
  • Matthias Pinter
  • Jaekyung Cheon
  • Yi-Hsiang Huang
  • Pei-Chang Lee
  • Samuel Phen
  • Anuhya Gampa
  • Anjana Pillai
  • Caterina Vivaldi
  • Francesca Salani
  • Gianluca Masi
  • Natascha Roehlen
  • Robert Thimme
  • Arndt Vogel
  • Martin Schönlein
  • Johann von Felden
  • Kornelius Schulze
  • Henning Wege
  • Peter R Galle
  • Masatoshi Kudo
  • Lorenza Rimassa
  • Amit G Singal
  • Paul El Tomb
  • Susanna Ulahannan
  • Alessandro Parisi
  • Hong Jae Chon
  • Wei-Fan Hsu
  • Bernardo Stefanini
  • Elena Verzoni
  • Raffaele Giusti
  • Antonello Veccia
  • Annamaria Catino
  • Giuseppe Aprile
  • Pamela Francesca Guglielmini
  • Marilena Di Napoli
  • Paola Ermacora
  • Lorenzo Antonuzzo
  • Ernesto Rossi
  • Francesco Verderame
  • Fable Zustovich
  • Corrado Ficorella
  • Francesca Romana Di Pietro
  • Nicola Battelli
  • Giorgia Negrini
  • Francesco Grossi
  • Roberto Bordonaro
  • Stefania Pipitone
  • Maria Banzi
  • Serena Ricciardi
  • Letizia Laera
  • Antonio Russo
  • Ugo De Giorgi
  • Luigi Cavanna
  • Mariella Sorarù
  • Vincenzo Montesarchio
  • Paola Bordi
  • Leonardo Brunetti
  • Carmine Pinto
  • Melissa Bersanelli
  • Calogero Cammà
  • Alessio Cortellini (Shared last author)
  • David J Pinato (Shared last author)

Abstract

BACKGROUND & AIMS: Immune-related liver injury (irLI) is commonly observed in patients with cancer treated with immune checkpoint inhibitors (ICIs). We aimed to compare the incidence, clinical characteristics, and outcomes of irLI between patients receiving ICIs for hepatocellular carcinoma (HCC) vs. other solid tumours.

METHODS: Two separate cohorts were included: 375 patients with advanced/unresectable HCC, Child-Pugh A class treated with first-line atezolizumab+bevacizumab from the AB-real study, and a non-HCC cohort including 459 patients treated with first-line ICI therapy from the INVIDIa-2 multicentre study. IrLI was defined as a treatment-related increase of aminotransferase levels after exclusion of alternative aetiologies of liver injury. The incidence of irLI was adjusted for the duration of treatment exposure.

RESULTS: In patients with HCC, the incidence of any grade irLI was 11.4% over a median treatment exposure of 4.4 months (95% CI 3.7-5.2) vs. 2.6% in the INVIDIa-2 cohort over a median treatment exposure of 12.4 months (95% CI 11.1-14.0). Exposure-adjusted-incidence of any grade irLI was 22.1 per 100-patient-years in patients with HCC and 2.1 per 100-patient-years in patients with other solid tumours (p <0.001), with median time-to-irLI of 1.4 and 4.7 months, respectively. Among patients who developed irLI, systemic corticosteroids were administered in 16.3% of patients with HCC and 75.0% of those without HCC (p <0.001), and irLI resolution was observed in 72.1% and 58.3%, respectively (p = 0.362). In patients with HCC, rates of hepatic decompensation and treatment discontinuation due to irLI were 7%. Grade 1-2 irLI was associated with improved overall survival only in patients with HCC (hazard ratio 0.53, 95% CI 0.29-0.96).

CONCLUSIONS: Despite higher incidence and earlier onset, irLI in patients with HCC is characterised by higher rates of remission and lower requirement for corticosteroid therapy (vs. irLI in other solid tumours), low risk of hepatic decompensation and treatment discontinuation, not negatively affecting oncological outcomes.

IMPACT AND IMPLICATIONS: Immune-related liver injury (irLI) is common in patients with cancer receiving immune checkpoint inhibitors (ICIs), but whether irLI is more frequent or it is associated with a worse clinical course in patients with hepatocellular carcinoma (HCC), compared to other tumours, is not known. Herein, we compared characteristics and outcomes of irLI in two prospective cohorts including patients treated with ICIs for HCC or for other oncological indications. irLI is significantly more common and it occurs earlier in patients with HCC, also after adjustment for duration of treatment exposure. However, outcomes of patients with HCC who developed irLI are not negatively affected in terms of requirement for corticosteroid therapy, hepatic decompensation, treatment discontinuation and overall survival.

Bibliographical data

Original languageEnglish
ISSN0168-8278
DOIs
Publication statusPublished - 03.2024

Comment Deanary

Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.

PubMed 37972660