The spectrum, incidence, kinetics and management of endocrinopathies with immune checkpoint inhibitors for metastatic melanoma. Issue 2 (February 2018)

• Record Type: Journal Article
• Authors: Scott, Emma S; Long, Georgina V; Guminski, Alexander; Clifton-Bligh, Roderick J; Menzies, Alexander M; Tsang, Venessa H
• Is Part Of: European journal of endocrinology. Volume 178:Issue 2(2018)
• Page Start: 173
• Page End: 180
• Publication Date: 2018-02
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1530/EJE-17-0810
• Languages: English
• ISSNs: 0804-4643

Abstract

Abstract : Objective: Endocrine immune-related adverse events (endocrinopathies) are increasingly prevalent with the use of immune checkpoint inhibitors for the treatment of metastatic melanoma and other malignancies. There are no evidence-based guidelines for the screening or management of such patients. To describe the spectrum, incidence, kinetics and management of endocrinopathies with immune checkpoint inhibitors. Design: A prospective study conducted at Melanoma Institute Australia between April 2014 and October 2015. Methods: A total of 177 patients were treated with (a) ipilimumab ( n = 15), (b) anti-PD-1 (nivolumab, pembrolizumab) ( n = 103) or (c) combination ipilimumab and anti-PD-1 ( n = 59) and were screened and managed for the subsequent endocrinopathies. The main outcome measures were the incidence and kinetics of endocrinopathy by immunotherapy drug class. Results: Thirty-one patients (18%) developed an endocrine immune-related adverse event (thyroid dysfunction: 14%, hypophysitis: 6% and autoimmune diabetes: 0.6%). Combination immunotherapy was more likely to result in a single or multiple endocrinopathy compared to anti-PD-1 monotherapy (27% vs 9% and 7% vs 0% respectively, P < 0.01). Endocrinopathies occurred after a median of 8 weeks from treatment commencement (range: 12–225 days), with combination immunotherapy resulting in significantly earlier onset compared to ipilimumab (median: 30 vs 76 days, P = 0.046). The majority of endocrinopathies were identified in asymptomatic patients with hormonal screening. There were no baseline predictors for endocrinopathy. Conclusions: Combination immunotherapy has a greater risk of development of endocrinopathy compared to anti-PD-1 monotherapy. Regular biochemical profiling of patients, particularly within the first twelve weeks, results in early detection of endocrinopathy to minimise morbidity.