Clinical spectrum and evolution of immune-checkpoint inhibitors toxicities over a decade—a worldwide perspective

Gougis, Paul; Jochum, Floriane; Abbar, Baptiste; Dumas, Elise; Bihan, Kevin; Lebrun-Vignes, Bénédicte; Moslehi, Javid; Spano, Jean-Philippe; Laas, Enora; Hotton, Judicael; Reyal, Fabien; Hamy, Anne-Sophie; Salem, Joe-Elie

doi:10.1016/j.eclinm.2024.102536

eClinicalMedicine

2024

DOI: 10.1016/j.eclinm.2024.102536

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Clinical spectrum and evolution of immune-checkpoint inhibitors toxicities over a decade—a worldwide perspective

Paul Gougis,

Floriane Jochum,

Baptiste Abbar

et al.

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2024

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Cited by 15 publications

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“…35,36 Although infrequent (about 1% of treated patients), ICI myocarditis can be fatal and reporting has only increased due to the growing use of ICI, often in combination. [37][38][39][40] Despite the clear correlation between autoimmune factors and myocarditis, the responsible autoantigens and underlying mechanisms remain poorly understood. Providing a potential clue, the α-MyHC (α isoform of myosin heavy chain), encoded by the gene MYH6, has recently emerged as a heart-specific autoantigen contributing to ICI myocarditis.…”

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confidence: 99%

Autoimmune Myocarditis, Old Dogs and New Tricks

Won,

Song,

Kalinoski

et al. 2024

Circulation Research

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Autoimmunity significantly contributes to the pathogenesis of myocarditis, underscored by its increased frequency in autoimmune diseases such as systemic lupus erythematosus and polymyositis. Even in cases of myocarditis caused by viral infections, dysregulated immune responses contribute to pathogenesis. However, whether triggered by existing autoimmune conditions or viral infections, the precise antigens and immunologic pathways driving myocarditis remain incompletely understood. The emergence of myocarditis associated with immune checkpoint inhibitor therapy, commonly used for treating cancer, has afforded an opportunity to understand autoimmune mechanisms in myocarditis, with autoreactive T cells specific for cardiac myosin playing a pivotal role. Despite their self-antigen recognition, cardiac myosin-specific T cells can be present in healthy individuals due to bypassing the thymic selection stage. In recent studies, novel modalities in suppressing the activity of pathogenic T cells including cardiac myosin-specific T cells have proven effective in treating autoimmune myocarditis. This review offers an overview of the current understanding of heart antigens, autoantibodies, and immune cells as the autoimmune mechanisms underlying various forms of myocarditis, along with the latest updates on clinical management and prospects for future research.

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confidence: 99%

Autoimmune Myocarditis, Old Dogs and New Tricks

Won,

Song,

Kalinoski

et al. 2024

Circulation Research

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Immune checkpoint inhibitors-associated cranial nerves involvement: a systematic literature review on 136 patients

Pichon,

Aigrain,

Lacombe

et al. 2024

J Neurol

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Objective Describe the demographic data and clinical phenotype of cranial palsy induced by immune checkpoint inhibitors (CNP-ICI). Methods A systematic literature review of the literature was performed in Pubmed, Web of Science, and Embase, including 68 articles and 136 patients (PROSPERO no. CRD42024517262). Results Out of the 1205 articles screened, 68 articles were included after fulfilling the inclusion criteria, for a total of 136 patients. All articles were case reports and case series. In the cohort studied, 52% of patients were treated with anti PD-1/PDL-1 therapies, 14% with anti CTLA-4 therapies, and 34% with a combination of anti CTLA-4 and anti PD-1/PDL-1 therapies. The facial nerve was the most affected cranial nerve, involved in 38% of cases, followed by the optic nerve (35%), the cochleovestibular nerve (12%), and the abducens nerve (10%). The median time from the initial immune checkpoint inhibitor (ICI) injection to the onset CNP-ICI was 10 weeks (IQR 4–20). Magnetic resonance imaging demonstrated contrast enhancement or abnormal signal of the affected nerve in 43% of cases. Cerebrospinal fluid analysis indicated lymphocytic pleocytosis in 59% of cases. At the onset of immune-related adverse events, 89% of patients discontinued immunotherapy, and 92% received treatment for CNP-ICI. Treatment regimens included corticosteroids in 86% of cases, intravenous immunoglobulin in 21%, and plasma exchange in 5.1%. Among the whole population, 33% achieved recovery, 52% showed clinical improvement, 16% remained stable, and 3% experienced worsening of their condition. Rechallenge with immunotherapy was significantly associated with the emergence of new immune-related Adverse Events (irAEs). Conclusion ICI therapy may lead to cranial nerve involvement, particularly affecting the facial nerve, typically presenting around 10 weeks after treatment initiation. While corticosteroid therapy often resulted in patient improvement, rechallenging with ICIs were associated with new irAEs.

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Co-design of an electronic patient-reported outcome symptom monitoring system for immunotherapy toxicities

Lai-Kwon,

Rutherford,

Best

et al. 2024

Support Care Cancer

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Clinical spectrum and evolution of immune-checkpoint inhibitors toxicities over a decade—a worldwide perspective

Cited by 15 publications

References 32 publications

Autoimmune Myocarditis, Old Dogs and New Tricks

Autoimmune Myocarditis, Old Dogs and New Tricks

Immune checkpoint inhibitors-associated cranial nerves involvement: a systematic literature review on 136 patients

Co-design of an electronic patient-reported outcome symptom monitoring system for immunotherapy toxicities

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