학술논문
An algorithm based on immunotherapy discontinuation and liver biopsy spares corticosteroids in two thirds of cases of severe checkpoint inhibitor‐induced liver injury.
Document Type
Article
Author
Riveiro‐Barciela, Mar; Barreira‐Díaz, Ana; Salcedo, María‐Teresa; Callejo‐Pérez, Ana; Muñoz‐Couselo, Eva; Iranzo, Patricia; Ortiz‐Velez, Carolina; Cedrés, Susana; Díaz‐Mejía, Nely; Ruiz‐Cobo, Juan Carlos; Morales, Rafael; Aguilar‐Company, Juan; Zamora, Ester; Oliveira, Mafalda; Sanz‐Martínez, María‐Teresa; Viladomiu, Lluis; Martínez‐Gallo, Mónica; Felip, Enriqueta; Buti, María
Source
Subject
*LIVER biopsy
*LIVER injuries
*IMMUNOTHERAPY
*CORTICOSTEROIDS
*ALGORITHMS
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Language
ISSN
0269-2813
Abstract
Summary: Background: There are few data on corticosteroids (CS)‐sparing strategies for checkpoint inhibitor (ICI)‐induced liver injury (ChILI). Aim: We aimed to assess the performance of a 2‐step algorithm for severe ChILI, based on ICI temporary discontinuation (step‐1) and, if lack of biochemical improvement, CS based on the degree of necroinflammation at biopsy (step‐2). Methods: Prospective study that included all subjects with grade 3/4 ChILI. Peripheral extended immunophenotyping was performed. Indication for CS: severe necroinflammation; mild or moderate necroinflammation with later biochemical worsening. Results: From 111 subjects with increased transaminases (January 2020 to August 2023), 44 were diagnosed with grade 3 (N = 35) or grade 4 (N = 9) ChILI. Main reason for exclusion was alternative diagnosis. Lung cancer (13) and melanoma (12) were the most common malignancies. ICI: 23(52.3%) anti‐PD1, 8(18.2%) anti‐PD‐L1, 3(6.8%) anti‐CTLA‐4, 10(22.7%) combined ICI. Liver injury pattern: hepatocellular (23,52.3%) mixed (12,27.3%) and cholestatic (9,20.5%). 14(32%) presented bilirubin >1.2 mg/dL. Overall, 30(68.2%) patients did not require CS: 22(50.0%) due to ICI discontinuation (step‐1) and 8/22 (36.4%) based on the degree of necroinflammation (step‐2). Biopsy mainly impacted on grade 3 ChILI, sparing CS in 8 out of 15 (53.3%) non‐improvement patients after ICI discontinuation. CD8+ HLA‐DR expression (p = 0.028), central memory (p = 0.046) were lower in CS‐free managed subjects, but effector‐memory cells (p = 0.002) were higher. Time to transaminases normalisation was shorter in those CS‐free managed (overall: p < 0.001, grade 3: p < 0.001). Considering our results, a strategy based on ICI discontinuation and biopsy for grade 3 ChILI is proposed. Conclusions: An algorithm based on temporary immunotherapy discontinuation and biopsy allows CS avoidance in two thirds of cases of severe ChILI. [ABSTRACT FROM AUTHOR]