Systemic glucocorticoid immunosuppression (gsISP) administered close to immune checkpoint inhibitor (ICI) initiation, at higher doses, or for prolonged periods may negatively affect overall survival (OS) in patients with cancer, according to a large multicentre cohort study.
Researchers analysed data from 39,258 patients treated with ICIs across two cohorts: 13,086 patients from Massachusetts General Hospital, Brigham and Women’s Hospital, and Dana-Farber Cancer Institute, and an independent validation cohort of 26,172 matched patients from the TriNetX database.
Immune checkpoint inhibitors have transformed outcomes for many cancers, but systemic glucocorticoids are frequently prescribed to manage immune-related adverse events, cancer symptoms, or comorbid inflammatory conditions. However, concerns remain that glucocorticoid-induced immunosuppression could compromise antitumour immune responses.
Longer Steroid Use Linked to Lower Survival
The investigators examined how the timing, dose, and duration of glucocorticoid exposure influenced survival outcomes among ICI recipients. Patients receiving gsISP within one year of starting ICIs experienced significantly worse OS compared with those who did not receive glucocorticoids. The strongest association was observed in patients exposed within one month of ICI initiation, who had approximately half the survival time of patients without glucocorticoid exposure (time ratio [TR]: 0.49; 95% CI: 0.45–0.54).
Dose-dependent effects were also identified. Prednisone-equivalent doses exceeding 60 mg/day were associated with a 37% reduction in survival duration. Similarly, glucocorticoid treatment lasting longer than seven days was linked to a 33% shorter OS.
Importantly, these findings were independently replicated in the external TriNetX validation cohort, strengthening the robustness of the results.
Researchers Urge Careful Steroid Use During Immunotherapy
The authors noted that the association between glucocorticoid exposure and poorer survival persisted regardless of the indication for steroid use, suggesting that immunosuppressive effects themselves may contribute to diminished ICI efficacy.
The findings highlight the importance of carefully balancing the clinical need for systemic glucocorticoids against potential impacts on immunotherapy outcomes. The researchers concluded that when glucocorticoids are necessary in patients receiving ICIs, clinicians should consider minimising exposure near treatment initiation and use the lowest effective dose for the shortest possible duration.
Reference
Wan G et al. Systemic Glucocorticoid Immunosuppression and Survival Among Immune Checkpoint Inhibitor Recipients. JAMA Netw Open. 2026; 9;(5):e2614323.
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