Immunosuppression with systemic glucocorticoids close to initiation of immune checkpoint inhibitor is associated with worse survival outcomes

1. Exposure to systemic glucocorticoid immunosuppression (gsISP) close to immune checkpoint inhibitor (ICI) initiation was associated with worse overall survival (OS). 

Evidence Rating Level: 2 (Good)

The introduction of ICIs has caused a dramatic shift in the management of several types of cancers and has led to improved OS in many cancers. However, the relationship between ICI effectiveness and immunosuppression with concurrent use of glucocorticoids, used for inflammatory symptoms or pre-existing autoimmune diseases, remains unclear. Specifically, the impact of the timing and duration of gsISP on ICI effectiveness has not been evaluated. This retrospective cohort study therefore sought to examine the association between timing and duration of gsISP on the OS of cancer patients treated with ICIs. 39,258 patients (mean[SD] age, 64.7[13.0] years; 46.4% female) from the United States with cancer treated with ICIs were included in the analysis. These patients were derived from two cohorts: the first included patients from Massachusetts General Hospital, Brigham and Women’s Hospital, and Dana-Farber Cancer Institute (MGBD cohort), while the second were derived from the TriNetX database. From the MGBD cohort, exposure to gsISP within 1 year of ICI initiation was associated with worse OS. Specifically, the worst OS was observed when gsISP exposure was within 1 month of ICI initiation (time ratio [TR], 0.49 [95% CI, 0.45-0.54]). Further, increased doses of gsISP were associated with worse OS, with a 19% (95% CI, 11%-28%) reduction in OS at 5 mg or more daily up to a 37% (95% CI, 25%-52%) reduction at 60 mg or more daily. Overall, this study found that exposure to gsISP close to ICI initiation was associated with worse overall survival. 

Click here to read this study in JAMA Network Open

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