Temporal trends and outcomes among patients admitted for immune-related adverse events: A single-center retrospective cohort study from 2011-2018.

BACKGROUND The aim of this study was to characterize severe irAEs seen among hospitalized patients and to examine risk factors for irAE admissions and clinically relevant outcomes, including length of stay, ICI discontinuation, readmission, and death. METHODS Patients who received ICI therapy (ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, or any ICI combination) at Massachusetts General Hospital (MGH) and were hospitalized at MGH following ICI initiation between January 1, 2011 and October 24, 2018 were identified using pharmacy and hospital admission databases. Medical records of all irAE admissions were reviewed and specialist review with defined criteria was performed. Demographic data, relevant clinical history (malignancy type and most recent ICI regimen), and key admission characteristics including dates of admission and discharge, immunosuppressive management, ICI discontinuation, readmission, and death were collected. RESULTS In total, 450 admissions were classified as irAE admissions and represent the study's cohort. Alongside the increasing use of ICIs at our institution the number of patients admitted to MGH for irAEs has gradually increased every year from 9 in 2011 to 92 in 2018. The hospitalization rate per ICI recipient has declined over that same time period (25.0% in 2011 to 8.5% in 2018). The most common toxicities leading to hospitalization in our cohort were gastrointestinal (GI; 30.7%; N=138), pulmonary (15.8%; N=71), hepatic (14.2%; N=64), endocrine (12.2%; N=55), neurologic (8.4%; N=38), cardiac (6.7%; N=30), and dermatologic (4.4%; N=20). Multivariable logistic regression revealed statistically significant increases in irAE admission risk for CTLA-4 monotherapy recipients (odds ratio [OR], 2.02; P<0.001) and CTLA-4 plus PD-1 combination therapy recipients (OR, 1.88; P<0.001), relative to PD-1/PD-L1 monotherapy recipients. CONCLUSION This study illustrates that cancer centers must be prepared to manage a wide variety of irAE types and that CTLA-4 and combination ICI regimens are more likely to cause irAE admissions that occur earlier after drug initiation.