Characteristics and outcomes of emergency presentations due to immune-mediated toxicities

Abstract

Background The prevalence of immune-mediated toxicities from immune checkpoint inhibitors (ICIs) is well described. However, the patient characteristics and outcomes of emergency presentations due to immune-mediated (IO) toxicity are less well known. Methods We reviewed all emergency presentations in patients treated with ICI at a single centre between May 2018 and February 2020. The aims were to describe and quantify patient and treatment characteristics, toxicity type and outcomes for IO toxicity. Results 1399 patients were treated with ICI and there were 597 emergency presentations in 370 patients. IO toxicity accounted for 191/597 (32%) of presentations. The median age was 64 years, the most common tumour types were melanoma (53%) and lung (22%) and the most common ICIs received were ipilimumab + nivolumab (42%), pembrolizumab (21%) and nivolumab (20%). Previous ≥ grade 2 IO toxicity was experienced in 75/191 (39%) of patients and 46/75 (61%) presented with the same IO toxicity. The most common diagnoses were colitis (38%), hepatitis (15%), and pneumonitis (14%) and 32/191 (17%) of patients had more than one IO toxicity. Patients with pneumonitis had longer median duration of stay of 8 days compared to 4 days for colitis and hepatitis (p=0.098). Five of 9 (56%) patients admitted to the Critical Care Unit had pneumonitis. Six patients died of toxicity within 30 days of presentation - 5 pneumonitis, 1 cerebral vasculitis. The 30-day mortality rate of patients with pneumonitis was 19% (5/26). The majority, 180/191 (94%) received steroids and 52/180 (29%) required second-line immunosuppression. Patients with colitis had the highest proportion requiring third or fourth-line immunosuppression. Conclusions The majority of patients with emergency presentations due to immune-mediated toxicity were being treated with combination immunotherapy for melanoma. More than a third had previous ≥ grade 2 immune-mediated toxicity and over one quarter of patients treated with steroids required second-line immunosuppression. These data allow better identification of patients likely to require admission and inform planning for acute oncology services.