Characteristics and outcomes of immunotherapy-related liver injury in patients with hepatocellular carcinoma versus other advanced solid tumours
- Autori: Celsa, Ciro; Cabibbo, Giuseppe; Fulgenzi, Claudia A.M.; Scheiner, Bernhard; D'Alessio, Antonio; Manfredi, Giulia F.; Nishida, Naoshi; Ang, Celina; Marron, Thomas U.; Saeed, Anwaar; Wietharn, Brooke; Pinter, Matthias; Cheon, Jaekyung; Huang, Yi-Hsiang; Lee, Pei-Chang; Phen, Samuel; Gampa, Anuhya; Pillai, Anjana; Vivaldi, Caterina; Salani, Francesca; Masi, Gianluca; Roehlen, Natascha; Thimme, Robert; Vogel, Arndt; Schönlein, Martin; von Felden, Johann; Schulze, Kornelius; Wege, Henning; Galle, Peter R.; Kudo, Masatoshi; Rimassa, Lorenza; Singal, Amit G.; El Tomb, Paul; Ulahannan, Susanna; Parisi, Alessandro; Chon, Hong Jae; Hsu, Wei-Fan; Stefanini, Bernardo; Verzoni, Elena; Giusti, Raffaele; Veccia, Antonello; Catino, Annamaria; Aprile, Giuseppe; Guglielmini, Pamela Francesca; Di Napoli, Marilena; Ermacora, Paola; Antonuzzo, Lorenzo; Rossi, Ernesto; Verderame, Francesco; Zustovich, Fable; Ficorella, Corrado; Di Pietro, Francesca Romana; Battelli, Nicola; Negrini, Giorgia; Grossi, Francesco; Bordonaro, Roberto; Pipitone, Stefania; Banzi, Maria; Ricciardi, Serena; Laera, Letizia; Russo, Antonio; De Giorgi, Ugo; Cavanna, Luigi; Sorarù, Mariella; Montesarchio, Vincenzo; Bordi, Paola; Brunetti, Leonardo; Pinto, Carmine; Bersanelli, Melissa; Camma', Calogero; Cortellini, Alessio; Pinato, David J.
- Anno di pubblicazione: 2024
- Tipologia: Articolo in rivista
- OA Link: http://hdl.handle.net/10447/638637
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.