Corticosteroids for the management of immune-related adverse events in patients receiving checkpoint inhibitors

Abstract

Introduction Due to enhanced T-cell activity, immune checkpoint inhibitors cause immune-related adverse effects. Corticosteroids are the mainstay of immune-related adverse effect management but the optimal strategy has not been determined, putting patients at risk for steroid-related adverse effects and potentially decreased efficacy of immunotherapy. This study aims to characterize the use of corticosteroids for the management of immune-related adverse effect. Methods and materials A retrospective, single-center evaluation of patients receiving checkpoint inhibitors was conducted. The primary objective was to evaluate corticosteroid use for immune-related adverse effects, including starting dose, taper strategy, total duration, and resumption of immunotherapy. Secondary objective was to describe the incidence and significance of hyperglycemia. Results One hundred and three patients met inclusion criteria and experienced 123 immune-related adverse effects. Prednisone was used most commonly (67%) at an average starting dose of 0.88 mg/kg (range 0.07-17.0). On average, steroid tapers began 9.2 days after initiation (range 0-89) and were continued for a total of 84.2 days (range 3-693). In 21.1% of cases, checkpoint inhibitor therapy was not delayed and 68.6% resumed checkpoint inhibitors, while the patient was taking steroids (30.4 mg prednisone on average, range 5-80). On average, checkpoint inhibitor therapy was resumed 18.6 days after detection of immune-related adverse effect (range 0-150). Clinically relevant hyperglycemia occurred in 8.9%. Conclusion Utilization of steroids for immune-related adverse effect at our institution is highly variable. The majority of patients received prolonged courses of steroids and resumed checkpoint inhibitor therapy with concomitant steroids above recommended doses. Additional monitoring for hyperglycemia and other steroid associated adverse effects should be considered.

Management of Immunotherapy-Related Toxicities, Version 1.2019, NCCN Clinical Practice Guidelines in Oncology

“…Hyperglycemia, gastritis, opportunistic bacterial or fungal infections, and osteoporosis can occur with a longer-term systemic corticosteroid. [102][103][104][105][106][107] The panel recommends blood glucose monitoring and various prophylactic measures. For patients at higher risk of developing gastritis (ie, those taking nonsteroidal anti-inflammatory drugs or anticoagulants), histamine 2 blockers or proton pump inhibitors can be given during steroid therapy.…”

Glucocorticoid use and complications following immune checkpoint inhibitor use in melanoma

“…21 While the proportion of patients receiving corticosteroids for IRAEs varied slightly between the studies, corticosteroids were generally prescribed for around one-third of patients, comparable to the results observed in this audit. 21,22 Glucocorticoid use after checkpoint inhibitors…”

Use of glucocorticoids in the management of immunotherapy‐related adverse effects

“…When treating grade 3-4 irAEs, the initial treatment usually requires at least 1-2 mg/kg of prednisone, and a total course duration of 4-6 weeks or longer. 13,14 Medium-acting GCS, such as prednisone or methylprednisolone, are often selected. Dexamethasone also has strong anti-inflammatory effects, but its half-life is long, and it is difficult to control the adverse effects when it is used for a long time.…”

“…14 In addition, patients should avoid contact with infected patients or infection sources, and attention to diet should be given to prevent substantial weight gain. 13 The risk of infection after GCS therapy is associated with a decrease in blood CD4+ T cell count. It is necessary to monitor the changes in patients' symptoms in order to detect opportunistic infections.…”