Impact of Age on Rheumatic Immune-related Adverse Events: Experience from the Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO).

Abstract

Objective: Immune checkpoint inhibitors (ICI) have revolutionized cancer outcomes but are limited by immunerelated adverse events (irAE), including rheumatic irAEs (Rh-irAE). Aging is associated with increased inflammation, referred to as "inflamm-aging". In this study, we explore the impact of age on severity, frequency, and treatment of Rh-irAEs.

Methods: Adults with new Rh-irAEs after ICI exposure are followed prospectively across 10 Canadian sites as part of the CanRIO prospective cohort. In this study of patients seen between January 2020 and March 2023, we compare the severity of Rh-irAE and number of irAE between patients ≥65 years and <65 years and explore potential epidemiologic, treatment-related, and phenotypic differences between the older and younger patients.

Results: A total of 139 patients with de novo Rh-irAEs were included, 58 in the "younger" (<65 years) and 81 in the "older" (≥65 years) group. There were no significant differences in severity of Rh-irAE (p=0.84) or number of irAEs (p=0.21), although there was a non-significant trend towards more older patients than younger patients with ≥3 irAEs (24% vs. 14%). Types of treatment for Rh-irAEs were similar between the groups. ICI continuation did not differ. Within the ICI-inflammatory arthritis (ICI-IA) subgroup, there was also no significant difference in the incidence of severe Rh-irAEs (p=0.51).

Conclusion: Similar numbers of overall irAE and severity of Rh-irAE were observed between older vs. younger patients who developed Rh-irAE after treatment with ICI therapy, suggesting that "inflamm-aging" does not play a significant role in Rh-irAEs. Larger studies are needed to explore potential differences in patient phenotypes.