Journal article
Personalized Cytokine-Directed Therapy With Tocilizumab for Refractory Immune Checkpoint Inhibitor-Related Cholangiohepatitis.
- Moi L Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
- Bouchaab H Service of Medical Oncology, Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
- Mederos N Service of Medical Oncology, Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
- Nguyen-Ngoc T Service of Medical Oncology, Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
- Perreau M Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; University Hospital of Lausanne, Lausanne, Switzerland.
- Fenwick C Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
- Vaucher J University Hospital of Lausanne, Lausanne, Switzerland; Department of Medicine, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
- Sempoux C University Hospital of Lausanne, Lausanne, Switzerland; Institute of Pathology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
- Peters S Service of Medical Oncology, Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland; University Hospital of Lausanne, Lausanne, Switzerland.
- Obeid M Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; University Hospital of Lausanne, Lausanne, Switzerland; Vaccine and Immunotherapy Center, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland. Electronic address: michel.obeid@chuv.ch.
- 2020-09-21
Published in:
- Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. - 2020
Anti–IL-6 therapy
Immune checkpoint inhibitor–related cholangitis
Immune checkpoint inhibitor–related hepatitis
Immune-related adverse events
English
INTRODUCTION
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
- Language
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- English
- Open access status
- closed
- Identifiers
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- DOI 10.1016/j.jtho.2020.09.007
- PMID 32956849
- Persistent URL
- https://sonar.ch/global/documents/239281
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