Abstract
Abstract only
e21010
Background: Despite significant gains from systemic immunotherapy, prompt recognition and management of immune related adverse events (irAEs) remains key to minimising acute and chronic morbidity, and can sometimes allow treatment to be re-initiated. Active management of irAEs is corticosteroid based, with additional immunosuppressants used for steroid-refractory toxicity. Although the majority of irAEs resolve promptly, prolonged steroid exposure is required to maintain irAE control. Patients are therefore frequently exposed to cumulative high doses of steroids that in turn can be associated with significant long-term morbidity. Methods: Melanoma patients treated at Mount Vernon Cancer Centre (UK) with ipilimumab, pembrolizumab or combination ipilimumab and nivolumab; who were managed for checkpoint inhibitor-induced colitis had their corticosteroid exposure calculated. Data was collected on patient characteristics, onset of colitis and the subsequent use of corticosteroids, immunosuppressant and anti-TNFα agents until complete resolution of symptoms. Results: Of 137 patients, 18 (13.1%) had grade 3-4 colitis. Median time to onset of colitic symptoms was 13 days (IQR 7-20) with 8 (44%) requiring intravenous corticosteroid. Median time from commencement of steroid treatment to grade 1 colitis was 11.5 days (IQR 6.75-25.25), with resolution of symptoms seen at a median of 43 days. Median total corticosteroid exposure was 3000mg oral prednisolone equivalent (range 540-7580mg) with median duration of corticosteroid exposure being 103.5 days (IQR 67-136). 8 patients experienced flare of colitis during corticosteroid dose reduction. In all cases of colitis flare, the anti-TNFα agent infliximab resulted in improvement to grade 1 toxicity within 48 hours. Conclusions: Patients requiring treatment with corticosteroids for checkpoint inhibitor induced colitis are exposed to high doses of corticosteroids for prolonged periods of time, with the potential for significant steroid-associated sequelae. Alternative steroid-sparing regimens to manage checkpoint inhibitor induced autoimmune toxicities are required.