Systemic Glucocorticoid Immunosuppression and Survival Among Immune Checkpoint Inhibitor Recipients

Importance: Systemic glucocorticoid immunosuppression (gsISP) is commonly used among patients receiving immune checkpoint inhibitor (ICI) therapy, but the associations of gsISP timing, dose, and duration with overall survival (OS) remain incompletely characterized. Objective: To examine the associations of gsISP timing, dose, and duration with OS among ICI recipients. Design, Setting, and Participants: This retrospective cohort study included ICI recipients treated at Massachusetts General Hospital, Brigham and Women's Hospital, and Dana-Farber Cancer Institute (MGBD) from May 31, 2015, through October 11, 2021, and matched ICI recipients from the TriNetX database from April 30, 2010, through October 11, 2021, for independent validation. The TriNetX cohort was matched 2:1 to the MGBD cohort using propensity scores based on patient baseline characteristics and year of ICI initiation. Exposure: gsISP, evaluated according to timing relative to ICI initiation, prednisone-equivalent dose, and duration of exposure. Main Outcomes and Measures: The main outcome was OS. Multivariable accelerated failure time models were used to estimate time ratios (TRs) and 95% CIs, with TR values less than 1 indicating shorter survival. Results: This study included 39 258 patients, with 13 086 in the MGBD cohort and 26 172 in the TriNetX cohort. In the MGBD and TriNetX cohorts, 53.6% and 55.4% of patients were men, and 63.6% and 64.2% were younger than 70 years (mean [SD] age, 64.7 [13.0] years and 64.9 [12.6] years), respectively. In the MGBD cohort, patients who received gsISP within 1 year of ICI initiation had worse OS compared with patients not treated with gsISP, with the most pronounced association observed among patients receiving gsISP within 1 month of ICI initiation (TR, 0.49 [95% CI, 0.45-0.54]). Higher doses and longer durations were also associated with shorter OS; dosages greater than 60 mg/d were associated with 37% (95% CI, 25%-52%) shorter OS, and durations longer than 7 days were associated with 33% (95% CI, 12%-49%) shorter OS. These findings were independently validated in the TriNetX cohort. Conclusions and Relevance: In this cohort study of ICI recipients, 3 factors were associated with worse OS: gsISP near ICI initiation, higher gsISP dose, and longer gsISP duration, regardless of indication. These findings may provide clinically relevant information to guide gsISP management among ICI recipients.