Effect of initial corticosteroid doses and second-line immunosuppressants on overall duration of corticosteroid therapy for immune-related adverse events in gastrointestinal tumors.

Abstract

824 Background: Immune checkpoint inhibitors (ICIs) have improved survival in patients with cancer but can also cause immune-related adverse events (irAEs). The clinical benefits of adherence to the irAE guidelines are unclear. This study aims to evaluate whether adhering to these guidelines improves irAE outcomes. Methods: We retrospectively reviewed patients with gastrointestinal cancer who developed irAEs after receiving ICIs between June 2017 and August 2024. The use of corticosteroids and second-line immunosuppressants was evaluated based on adherence to contemporary international guidelines (NCCN, ESMO, and ASCO). IrAE recovery was defined as the complete discontinuation of corticosteroids together with restoration of the affected organ function to baseline levels. A multivariable logistic regression analysis was performed to evaluate factors associated with achieving irAE recovery within 70 days. The cutoff of 70 days was chosen because the median time from the initiation of corticosteroid therapy to irAE recovery in this cohort was 70 days. Results: Of the 737 patients treated with ICIs, 127 (17.2%) developed irAEs, including 29 (22.8%) who experienced multiple irAEs. Excluding 53 endocrine irAEs, 100 of 116 (86.2%) were treated with corticosteroids. Among the 100 irAEs, there were two groups; 74 irAEs managed according to guidelines (Group A) and 26 managed in a non–guideline-adherent manner (Group B). There were significant differences in second-line immunosuppressant use between the two groups ( p = 0.0327). The most common irAEs were pneumonitis (n = 34, 20.1%), followed by colitis (n = 21, 12.4%), hepatitis (n = 15, 8.9%), and dermatitis (n = 15, 8.9%). Fifty-four irAEs (54.0%) were grade 3 or 4. There was no statistically significant difference in the irAE recovery rate between the two groups, with rates of 87.8% (65/74) and 76.9% (20/26), respectively. However, Group A required a significantly shorter duration of corticosteroid treatment than Group B (median: 63.0 days vs 146.5 days, p < 0.001). This finding was consistent across irAE grades and subgroups requiring second-line therapies. Among 23 patients who received second-line therapies, initiating treatment within two weeks after the start of corticosteroid therapy was associated with fewer relapses (0/14, 0% vs 5/9, 55.6%; p = 0.0407) and shorter corticosteroid treatment duration (median: 49.0 days vs 132.5 days, p < 0.001). Multivariable analysis revealed that guideline adherence was the only factor significantly associated with achieving irAE recovery within 70 days (odds ratio = 4.57, p = 0.0129). Conclusions: Adequate initial corticosteroid doses and the appropriate use of second-line immunosuppressants resulted in a significantly shorter corticosteroid treatment duration.