Association between age, risk of severe (Grade 3-4) immune-related adverse events (sirAE), and mortality in patients receiving immune checkpoint inhibitors (ICI).

Abstract

6597 Background: ICI are used in the treatment of advanced malignancies with on-target adverse events of non-tumor inflammation. Many studies have shown conflicting safety results with regard to older vs younger adults where 65 - 70 years of age has been used as the discrete cut-off variable. We sought to investigate the incidence and the association between age and sirAE using age as a continuous variable at a large tertiary cancer center. Methods: Under IRB approval, our ICI outcomes database was queried for those who were hospitalized and received an immunosuppressant. Charts were individually reviewed to identify hospital admissions due to a sirAE (a grade 3 or 4 AE per CTCAE v4.0) and all-cause mortality at 12 months post ICI start. Non-linear analyses using Cox regression models with penalized smoothed splines were performed to explore association between age and sirAE. Results: There were 6.3% of 1043 patients who had a sirAE, and a total of 83 sirAE events. Mean age was 64± 13 years.ICI included anti-PD-1 (77.8%), anti-CTLA-4 (18.1%), and anti PD-L1 (4.1%). Pts with sirAE had a thirty day, and one year mortality of 12% and 49%, respectively. These events included: colitis (30.1%), pneumonitis (16.9%), hepatitis (10.8%), hypophysitis (6%), and thyroiditis (6%). There were 5 neurologic and 4 myocarditis/myositis sirAEs. The 1-year cumulative incidences of sirAE and all-cause mortality were 8.4%, and 48%, respectively. Spline analysis showed a U-shaped association between age and hazard of sirAE (P = 0.03). Every 10 years above age 60 was associated with increased sirAE (HR 1.65 [1.14-2.40], P = 0.008), while every 10 years below 60 was associated with increased sirAE (HR 1.50 [0.99-2.27], P = 0.054). However, age and mortality showed a linear association (P = 0.003). Conclusions: We observed a curvilinear U-shaped association between age and the risk of sirAE, with minimum risk at age of 60, compared with a linear relationship between age and mortality. Further studies are needed to understand this relationship and its impact on outcomes, clinical care, and underlying host immune context.