Princess Alexandra Hospital, Brisbane, Australia
Emily Horan , Melissa Arneil , Wen Xu , Victoria Atkinson
Background: Immune checkpoint inhibitors (CPI) are widely used in metastatic melanoma (MM), where it has markedly improved survival outcomes. ICI induced autoimmune adverse reactions (irAE) manifest in all organ systems and are due to over-activation of the immune system. Clinically relevant irAE are colitis and hepatitis as drivers of morbidity and mortality. Methods: Data was collected from a single centre (Princess Alexandra Hospital) from the electronic medical records system and immunotherapy prescribing software. Patient demographics, treatments, complications and outcomes were recorded from 2016-2019. Eligible patients had to have received immunotherapy (pembrolizumab, ipilimumab, or nivolumab) and experienced colitis or hepatitis toxicity. Trial patients were excluded. Results: The cohort of 337 patients who had received immune therapy, 18% (n = 61) had hepatitis or colitis, mean age was 56 years, 64% male. The majority were stage 4d 28% (n = 17). Braf wildtype accounted for 56% (n = 34). The highest rates of irAE occurred on combination ipilimumab and nivolumab 56% (n = 34), 10% nivolumab (n = 6), 3% (n = 2) ipilimumab, and 31% (n = 19) pembrolizumab monotherapy. Colitis affected 61% of patients (n = 37), 30% (n = 18) were grade 3 severity. Hepatitis affected 48% (n = 29), 18% (n = 32) were grade 1. The majority required oral steroids (80%, n = 49), followed by intravenous steroids (51%, n = 31), infliximab (18%, n = 11) and mycophenolate in 5% (n = 3). Hospitalisation occurred in 56% (n = 34), 20% (n = 12) requiring treatment cessation. Progressive disease occurred in 62% (n = 38), and 13% (n = 8) had a complete response. Conclusions: The findings of this analysis mirror current literature with immunotherapies used, rates and severity of irAE. The management of irAE also aligned with current guidelines. Further research is required to investigate patient factors increasing the risk of developing irAE, and ideal treatment regimens. Analysing this large cohort, the incidence of toxicity was 17%, predominantly colitis followed by hepatitis. Patients were severely impacted requiring significant interventions to manage toxicity, hospitalisation and morbidity.
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