The spectrum, incidence, kinetics and management of endocrinopathies with immune checkpoint inhibitors for metastatic melanoma

Abstract

ObjectiveEndocrine 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.DesignA prospective study conducted at Melanoma Institute Australia between April 2014 and October 2015.MethodsA 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.ResultsThirty-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.ConclusionsCombination 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.