The glucocorticoid toxicity index: Assessing corticosteroid toxicity in patients with immune-related adverse events from cancer immunotherapy for solid tumors.

Abstract

e24194 Background: Immune checkpoint inhibitors (ICIs) cause immune-related adverse events (irAEs) requiring systemic corticosteroids. The toxicity of glucocorticoids has not been studied in immuno-oncology, despite being the mainstay of irAE management. We applied the Glucocorticoid Toxicity Index (GTI), a validated, multidimensional tool developed to assess the duration and severity of steroid toxicity in rheumatology, as a comprehensive metric to evaluate the toxicity of corticosteroids at baseline and over time for irAEs. Methods: This exploratory secondary data use analysis utilized data from a set of Roche/Genentech trials with atezolizumab across multiple tumor types. Patients included were: corticosteroid-naive, had an irAE event within 7 days of initiating ICIs, and were treated with corticosteroids (IV/oral). Data was stored in a Snowflake based relational database to facilitate analysis using a mixture of SQL queries and Python code. The GTI score was computed according to methods detailed by Miloslavsky et al., 2017, where available. e.g. (BMI, BP, glucose levels, were directly included; while myopathy, infection, significant organ impairment, included as reported by the treating investigator.). Results: Our analysis included 558 atezolizumab treated patients across 32 clinical trials (primarily NSCLC 21.7%, melanoma 19.2%, and breast cancer 12.9%). Baseline GTI scores varied across patients (range: -18 to 262). GTI score varied with corticosteroid use, with corticosteroid initiation for irAEs resulting in a 236% increase in average GTI score (8.6 to 28.9) by day 168. Conversely, patients with low GTI scores (0 or lower) declined from 67% at corticosteroid initiation to 28% at day 168 post corticosteroid use. Patients with low baseline GTI scores ( < = 10) reduced from 77.96% to 48.75% at day 168. Further analysis is ongoing to identify baseline features (age, gender, ICI mono vs combination) that associate with GTI score, and the association between GTI and clinical outcomes (PFS and OS). Conclusions: In this analysis, we identify that the GTI score is assessable at baseline and longitudinally in ICI-treated patients, and correctly identifies the effects of corticosteroids for irAEs, in 558 ICI-treated patients. Thus, the GTI represents a potential novel baseline and longitudinal biomarker of corticosteroid toxicity for management of ICI-induced irAEs. This approach may be leveraged to implement risk stratification criteria to inform corticosteroid duration for irAEs, and assist clinicians in timing of second-line immunosuppression in those with high GTI scores +/- unacceptable toxicity risk from corticosteroids.