An algorithm based on immunotherapy discontinuation and liver biopsy spares corticosteroids in two thirds of cases of severe checkpoint inhibitor-induced liver injury
Riveiro Barciela, Mar (Universitat Autònoma de Barcelona. Departament de Medicina)
Barreira-Diaz, Ana (Hospital Universitari Vall d'Hebron)
Salcedo, Maria-Teresa (Hospital Universitari Vall d'Hebron)
Callejo, Ana (Hospital Universitari Vall d'Hebron)
Muñoz Couselo, Eva (Hospital Universitari Vall d'Hebron)
Iranzo, Patricia (Hospital Universitari Vall d'Hebron)
Ortiz Velez, Carolina (Hospital Universitari Vall d'Hebron)
Cedrés, Susana (Hospital Universitari Vall d'Hebron)
Díaz Mejía, Nely (Hospital Universitari Vall d'Hebron)
Ruiz Cobo, Juan Carlos (Hospital Universitari Vall d'Hebron)
Morales, Rafael (Hospital Universitari Vall d'Hebron)
Aguilar-Company, Juan (Hospital Universitari Vall d'Hebron)
Zamora, Ester (Hospital Universitari Vall d'Hebron)
Oliveira, Mafalda (Hospital Universitari Vall d'Hebron)
Sanz-Martínez, María Teresa (Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Viladomiu, Lluis (Universitat Autònoma de Barcelona. Departament de Medicina)
Martínez Gallo, Mónica (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Felip, Enriqueta (Hospital Universitari Vall d'Hebron)
Buti, Maria (Universitat Autònoma de Barcelona. Departament de Medicina)

Data:	2024
Resum:	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.
Nota:	Altres ajuts: acords transformatius de la UAB
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Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Alimentary Pharmacology and Therapeutics, Vol. 59 Núm. 7 (april 2024) , p. 865-876, ISSN 1365-2036

DOI: 10.1111/apt.17898

12 p, 940.4 KB

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