Immune Checkpoint Inhibitor-Associated Primary Adrenal Insufficiency: WHO VigiBase Report Analysis

The oncologist

article

Virginie Grouthier¹  Bénédicte Lebrun-Vignes²  Melissa Moey⁴  Douglas B. Johnson⁴  Javid J. Moslehi⁴  Joe-Elie Salem²  Anne Bachelot⁵ 

[1] Department of Endocrinology, University of Bordeaux;Pharmacovigilance Unit, Department of Pharmacology, Unité de Cardio-Oncologie Sorbonne Université–Groupe de Recherche Clinique en Cardio-Oncologie (UNICO-GRECO), INSERM Centre d'Investigation Clinique (CIC)-1901, Pitié-Salpêtrière Hospital;Université Paris-Est Créteil (UPEC);Cardio-Oncology Program, Departments of Medicine and Pharmacology, Vanderbilt University Medical Center;Department of Endocrinology and Reproductive Medicine, Centre de Référence des Maladies Endocriniennes Rares de la Croissance and Centre de Référence des Pathologies Gynécologiques Rares, Institute of Cardiometabolism and Nutrition (ICAN), Pitié-Salpêtrière Hospital

关键词: Endocrine toxicity;    Immune checkpoint inhibitors;    Immune-related adverse events;    Immunotherapy;    Primary adrenal insufficiency;   

DOI  :  10.1634/theoncologist.2019-0555

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Background Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but may also trigger autoimmune adverse drug reactions (ADRs) referred to as immune-related adverse events (irAEs). Although endocrinopathies are among the most common form of irAEs, primary adrenal insufficiency (PAI) is infrequent and has only been published in case reports. The aim of this study was to identify and characterize the main features of PAI-irAE. Materials and Methods Suspected PAI-irAE cases were identified using VigiBase, the World Health Organization's pharmacovigilance database of individual case safety reports. Results From September 2, 2008, through October 5, 2018, a total of 50,108 ICI-associated ADRs were reported. Since 2008, there were 451 cases of PAI-irAE identified of which 45 were “definite PAI” and 406 “possible PAI.” Patients were mainly male (58.1%) with a median age of 66 years (range, 30–95). Indications of ICI were predominantly for melanoma (41.2%) and lung cancer (28.6%). The majority of patients were treated with ICI monotherapy (nivolumab: 44.3%, pembrolizumab: 11.7%, ipilimumab: 23.6%), and 17.9% were treated with ICI combination therapy. These events occurred with a median time to onset of 120 days (range, 6–576). ICI-associated PAI was associated with significant morbidity (≥90% severe) and mortality (7.3%). Fatality rates were similar in the subgroups of combination therapy versus monotherapy. There were no relevant differences in clinical or demographical characteristics and outcomes between “definite” versus “possible” PAI group. Conclusion Our study represents the largest clinical description and characterization of PAI-irAE. Although ICI-associated PAI is a rare adverse event, early recognition is important to implement corticosteroid treatment. Further studies are required to elucidate risk factors and reversibility of this rare but severe irAE. Clinical trial identification number . NCT03492242 Implications for Practice Immune checkpoint inhibitor (ICI)-associated primary adrenal insufficiency (PAI) is a rare adverse event that is important to recognize because it may be severe and life-threatening, requiring emergent and often lifelong hormonal replacement therapy. Awareness regarding this ICI-related endocrinopathy is strongly encouraged among clinicians in addition to patient education about common PAI symptoms that should prompt urgent medical evaluation. In clinical practice, close monitoring and investigation for PAI is crucial to allow for early management and to further define the pathophysiology and prognosis of ICI-PAI. Corticotrophin (adrenocorticotrophic hormone) circulating level evaluation may be often lacking but should be considered as part of the diagnostic workup to differentiate PAI from secondary (central) adrenal insufficiency.

【 授权许可】

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