Background Immune-related adverse events (irAEs) are serious side effects of immune checkpoint inhibitors (ICIs) for patients with advanced cancer. Understanding the epidemiology and risk factors for severe irAEs would be beneficial for patients and clinicians.
Methods We performed a retrospective review of cancer patients treated with ICIs using un-identifiable claims data from a nationwide US health insurance plan from January 3rd, 2011 to December 31st, 2019. Patients with an identified primary cancer and at least one administration of an ICI were included in the study. We defined severe irAE as any inpatient hospitalization with new immunosuppression within 2 years after initiation of ICI. The main outcomes were incidence of severe irAE in ICI therapy and factors associated with severe irAE occurrence. Multivariable logistic regression, including Charlson comorbidity index, age, gender, primary cancer, region, and zip code average income and unemployment, was used to model risk factors for severe irAE (table 1).
Results There were 14,378 patients followed over 19,177 patient-years identified with a primary cancer and at least 1 administration of ICI. 504 (3.5%) patients developed a severe irAE. The incidence of severe irAEs per patient ICI treatment year was 2.6%, rising from 0% (0/71) in 2011 to 3.7% (93/2486) in 2016 (figure 1). Combination immunotherapy (OR: 2.44, p < 0.001) and younger age (OR: 0.77, p < 0.001) were associated with increased odds of developing severe irAEs, whereas patients with non-lung cancer were associated with decreased odds of irAEs (melanoma OR: 0.70, p = 0.01, renal cell carcinoma OR: 0.71, p = 0.03, other cancers OR: 0.50, p < 0.001; figure 1). Sex, region, zip code income, and zip-code imputed unemployment were not associated with severe irAE incidence. Prednisone (72%) and methylprednisone (25%) were the most common immunosuppressive treatments identified in irAE hospitalizations.
Conclusions We found that 3.5% of patients initiating ICI therapy experienced severe irAEs requiring hospitalization and immunosuppression. The odds of severe irAEs were higher with younger age, treatment with combination ICI therapy (CTLA-4 and PD-1 or PD-L1), and lower for other cancers compared with patients on PD-1 or PD-L1 inhibitors with lung cancer. This evidence from the first nationwide study of severe irAEs in the US identified the real-world epidemiology, risk factors, and treatment patterns of severe irAEs in the US which may guide treatment selection and decisions for patients and clinicians.
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