Impact of age and frailty on acute care use during immune checkpoint inhibitor treatment

Purpose — Older and frail adults were under-represented in clinical trials evaluating ICIs, leading to a knowledge gap on their risk of acute care use and immune-related adverse events (irAEs). We performed a population-level study evaluating the impact of age and frailty among older adults receiving ICIs on acute care use and irAE-related hospitalizations.

Methods — Patients with cancer, age ≥ 65 initiating ICIs between June 2012-October 2018 (Ontario, Canada) were identified using systemic therapy administration data. The cohort was linked to other databases to obtain covariates and outcomes. Multivariable Cox proportional models evaluated the impact of age and frailty on acute care use and irAE-related hospitalizations.

Results — Among 2,737 patients, median age was 73 and 26% were pre-frail and 4% frail; 72% required acute care use, while 8% had an irAE-related hospitalization. Increasing frailty was associated with increased risk of acute care use (pre-frail vs robust, aHR = 1.20,95% CI[1.07-1.36], p = .003; frail vs robust, aHR = 1.45[1.12-1.86], p = .004), while age was not associated with acute care use. Increasing age was associated with reduced risk of irAE-related hospitalization (aHR = 0.97 per year[0.95-0.99], p = .01); patients age ≥ 80 compared to 65-69 had reduced risk of irAE-related hospitalization (aHR = 0.63[0.39-1.01], p = .05). Frailty was not associated with irAE-related hospitalizations. Associations remained consistent when evaluating age and frailty in the same models.

Conclusions — Age was associated with reduced risk of an irAE-related hospitalization but not acute care use, while increasing frailty was associated acute care use, but not irAE-related hospitalization. Age and frailty may need to be considered independently when evaluating their impact on toxicity among older adults receiving ICIs.