Personalized Cytokine-Directed Therapy With Tocilizumab for Refractory Immune Checkpoint Inhibitor-Related Cholangiohepatitis.

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State: Public
Version: Author's accepted manuscript
License: Not specified
Serval ID
serval:BIB_3FFE3BA356BB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Personalized Cytokine-Directed Therapy With Tocilizumab for Refractory Immune Checkpoint Inhibitor-Related Cholangiohepatitis.
Journal
Journal of thoracic oncology
Author(s)
Moi L., Bouchaab H., Mederos N., Nguyen-Ngoc T., Perreau M., Fenwick C., Vaucher J., Sempoux C., Peters S., Obeid M.
ISSN
1556-1380 (Electronic)
ISSN-L
1556-0864
Publication state
Published
Issued date
02/2021
Peer-reviewed
Oui
Volume
16
Number
2
Pages
318-326
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
For patients with corticosteroid (CS)-refractory immune checkpoint inhibitor-related cholangiohepatitis (irCH), no consensus exists regarding treatment, and outcomes remain poor. We evaluated the possibility of personalized treatment according to the patient's cytokine profile and the immunohistopathologic assessment of the predominant immune infiltrate type of liver tissue.
NSCLCs with CS-refractory irCH were analyzed by immunohistochemistry of liver biopsy specimen, serum cytokine panel, and assessment of peripheral blood mononuclear cell immune cell monitoring by mass cytometry.
A total of three consecutive patients with irCH were identified. We found a predominant T-cell infiltrate and an interferon-gamma or T helper 1 proinflammatory cytokine profile. Here, we report for the first time that a T-cell-targeted therapy with the interleukin (IL)-6 receptor-neutralizing antibody tocilizumab, which inhibits signaling downstream of interferon-gamma and several other Janus kinase-dependent cytokines, is an effective single cytokine-directed therapy for CS-refractory irCH. Three patients with severe, CS-refractory irCH who were treated with tocilizumab were found to have persistent clinical and biological remission.
Dysregulation of the IL-6/T-cell axis may contribute to the pathogenesis of CS-refractory irCH. Our observations suggest that IL-6 blockade seems to have promise in the treatment of CS-refractory irCH. The results from our three patients need to be confirmed in a larger patient population.
Keywords
Immune-related adverse events, anti-IL-6 therapy, immune checkpoint inhibitor-related cholangitis, immune checkpoint inhibitor-related hepatitis, Anti–IL-6 therapy, Immune checkpoint inhibitor–related cholangitis, Immune checkpoint inhibitor–related hepatitis
Pubmed
Web of science
Open Access
Yes
Create date
22/09/2020 15:22
Last modification date
17/04/2021 6:33
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