Immune-Related Adverse Events Requiring Hospitalization: Spectrum of Toxicity, Treatment, and Outcomes

Abstract

PURPOSE: Immune checkpoint inhibitors (ICIs) cause immune-related adverse events (irAEs). The proportion of patients who are hospitalized for irAEs and their spectrum, management, and outcomes are not well described. METHODS: We report the proportion of hospitalized patients in an academic center who were treated with ICIs from May to December 2017. Patient characteristics, toxicities, management, and outcomes for confirmed irAE admissions are reported. Associations between patient features and irAE hospitalizations are examined. RESULTS: Twenty-three percent (n = 100) of 443 patients who were admitted to an academic oncology center over 6 months had ever received ICIs. Of these patients, 41% were admitted for suspected irAEs and 23% were confirmed irAEs. IrAEs accounted for 5% of all oncology hospitalizations (n = 23). Ninety-one percent of patients with confirmed irAEs prompted a medicine subspecialist consultation, most commonly gastroenterology (22%). Fifteen patients (65%) had their irAEs improve/resolve, seven (30%) had worsening irAEs, and three (13%) died of their irAEs. The majority of patients (n = 20; 87%) discontinued ICIs after discharge. Among ICI-treated patients who required admission, an increased likelihood of irAE-related hospitalization was associated with patient age older than 65 years (odds ratio, 5.4; 95% CI, 1.6 to 17.8) and receipt of combination immunotherapy (OR, 6.8; 95% CI, 2.0 to 23.2). CONCLUSION: A notable proportion of ICI-treated patients are hospitalized for irAEs, and these patients have a high demand for multidisciplinary management. Older age and combination ICI treatment were associated with an increased risk of irAE-related hospitalization. Whereas these data are from an academic center and include patients in clinical trials, with expanding use of ICIs, these data have important implications for inpatient service planning and risk stratification.

Prediction of severe immune-related adverse events requiring hospital admission in patients on immune checkpoint inhibitors: study of a population level insurance claims database from the USA

“…Our study showed that the absolute incidence of irAEs requiring hospitalization in the study population increased over time from 2011 to 2019, a finding that is consistent with the increased use of ICI over that time period. We demonstrate that combination therapy is associated with increased odds of irAE requiring hospitalization, which is in agreement with prior findings that combination therapy 32 and CTLA-4 therapy 23 33–35 are associated with higher incidence of irAEs relative to PD-1 or PD-L1 treatment. The incidence of irAEs requiring hospitalization in this study was 3.5% overall, with 3.3% for patients receiving PD-1, 1.1% for patients receiving PD-L1, 3.9% for patients receiving CTLA-4 therapy, and 7.3% for patients on combination therapy.…”

“…In our study, average hospitalization length of stay for irAE patients was 6 days, which is consistent with previous study results. 32 Our study reports that patients with severe irAEs were more likely to have an ICU admission (OR 2.60, p<0.001), which is not a widely reported outcome in large scale ICI studies. 34 …”

Temporal Trends and Outcomes Among Patients Admitted for Immune-Related Adverse Events: A Single-Center Retrospective Cohort Study from 2011 to 2018

“…In investigating risk factors for irAE hospitalization, we found that CTLA‐4 therapy or combination ICI therapy was associated with a nearly twofold increase in irAE admission risk relative to PD‐1/PD‐L1 therapy. This is consistent with previous findings that combination ICI therapy is a risk factor for the occurrence of severe or life‐threatening irAEs, often requiring hospitalization [18, 19]. Furthermore, patients with severe toxicities caused by CTLA‐4 therapy and CTLA‐4 plus PD‐1 combination therapy were admitted significantly earlier in treatment (at 6 to 7 weeks) than those caused by PD‐1/PD‐L1 monotherapy (at 3 months).…”

Systemic therapy for elderly patients with non–small cell lung cancer: Where do we stand in 2019?

“…12 Although information regarding the development of immune-related adverse events (irAEs) in the SEER analysis by Youn et al 2 was limited, recent data have suggested that patient age >65 years may be a risk factor for the development of irAEs and may potentially increase the risk of hospitalization after receipt of immunotherapy. 13 Munchnik et al 7 reported that a disproportionate number of older patients required medical interventions to manage their irAEs compared with what was observed in previous clinical trials, along with a higher rate of treatment discontinuation. These findings highlight the inherent vulnerability of older adults and have significant implications with respect to cost-effectiveness and treatment decision making, which ultimately should be factored into the informed consent process.…”

“…This finding is concordant with recent reports demonstrating that immune checkpoint inhibitors can be administered with caution in patients who have autoimmune conditions . Although information regarding the development of immune‐related adverse events (irAEs) in the SEER analysis by Youn et al was limited, recent data have suggested that patient age >65 years may be a risk factor for the development of irAEs and may potentially increase the risk of hospitalization after receipt of immunotherapy . Munchnik et al reported that a disproportionate number of older patients required medical interventions to manage their irAEs compared with what was observed in previous clinical trials, along with a higher rate of treatment discontinuation.…”