Impact of age and frailty on acute care use during immune checkpoint inhibitor (ICI) treatment: A population-based study.
Authors: Eng Lawson , Sutradhar Rinku , Kaliwal Yosuf , Niu Yue , Liu Ning , Liu Ying , Powis Melanie Lynn , Liu Geoffrey , Peppercorn Jeffrey M. , Krzyzanowska Monika K. , Alibhai Shabbir M.H. 
Published: June 2022

12002

Background: ICIs are a common therapeutic option across solid tumors. However, older adults were poorly represented in clinical trials evaluating ICIs, especially those who are very old or frail. Although ICIs are better tolerated than chemotherapy, some patients develop immune related adverse events (irAEs) that may require hospitalization. We performed a population-level retrospective cohort study to evaluate the impact of age and frailty among older adults on acute care use and irAE related hospitalizations. Methods: We used administrative data deterministically linked across databases to identify a cohort of cancer patients > 65 years of age receiving ICIs from June 2012 to October 2018 in Ontario, Canada and obtained data on socio-demographic and clinical covariates, and acute care utilization. Acute care use was defined as an emergency department visit or hospitalization from initiation to 120 days after the last ICI dose; hospitalizations were classified as irAE related based on ICD-10 codes. Frailty was assessed using the McIsaac Frailty Index. Multivariable competing risk analyses with Fine Gray subdistribution hazards evaluated the impact of age and frailty on both acute care use and irAE hospitalizations adjusted for sex, rurality, BMI, autoimmune history, hospitalization within 60 days prior to starting ICI and comorbidity score. Results: Among 2737 patients, median age 73 (18% age > 80, 50% age 70-79); 43% received Nivolumab, 41% Pembrolizumab and 13% Ipilimumab; 53% had lung cancer, 34% melanoma. 70% were robust, 26% pre-frail and 4% frail. Most patients (1962; 72%) had an acute care episode during the window, while 212 (8%) had an irAE hospitalization. Older age was associated with reduced risk of being hospitalized due to an irAE when measured as a continuous variable (aHR 0.97 per year [0.95-0.99] p = 0.01). Older adults, age > 80 years were also less likely to be hospitalized due to an irAE (age 70-79 vs 65-69, aHR 0.92 [0.66-1.27] p = 0.61, age > 80 vs 65-69, aHR 0.63 [0.39-1.01] p = 0.05). Age was not associated with acute care use as a continuous or categorical variable. Increasing frailty was associated with increased risk of acute care use during ICI treatment (pre-frail vs robust, aHR 1.20 [1.07-1.36] p = 0.003; frail vs robust, aHR 1.45 [1.12-1.86] p = 0.004) but was not associated with irAE hospitalizations. When evaluating both age and frailty in the same model, the identified associations remained significant. Conclusions: Among older adults receiving ICIs, age was not associated with acute care use but may be associated with reduced risk of experiencing an irAE related hospitalization. In contrast, frailty was associated with risk of acute care use but was not associated with risk of an irAE related hospitalization. Age and frailty may need to be considered independently when evaluating their use as potential factors influencing toxicity risk among older adults receiving ICIs.