Systemic Glucocorticoid Immunosuppression and Survival Among Immune Checkpoint Inhibitor Recipients

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment.
• Systemic glucocorticoid immunosuppression (gsISP) is frequently used alongside ICI therapy.
• The impact of gsISP timing, dose, and duration on overall survival (OS) in ICI recipients requires further clarification.

Purpose of the Study:

• To investigate the association between gsISP timing, dose, and duration and OS in patients undergoing ICI therapy.
• To provide evidence-based guidance for managing gsISP in this patient population.

Main Methods:

• Retrospective cohort study utilizing data from Massachusetts General Hospital, Brigham and Women's Hospital, and Dana-Farber Cancer Institute (MGBD) and the TriNetX database.
• Propensity score matching was employed to create comparable cohorts for validation.
• Multivariable accelerated failure time models were used to analyze OS, with time ratios (TRs) calculated.

Main Results:

• Analysis of 39,258 patients revealed that gsISP initiated within 1 year of ICI therapy was associated with worse OS, particularly when initiated within 1 month (TR, 0.49).
• Higher gsISP doses (>60 mg/d) and longer durations (>7 days) were also significantly associated with reduced OS.
• These findings were consistent across both the MGBD and TriNetX cohorts.

Conclusions:

• Timing, dose, and duration of gsISP are critical factors influencing OS in patients receiving ICI therapy.
• gsISP administered close to ICI initiation, at higher doses, or for longer durations is associated with poorer survival outcomes.
• These results underscore the need for careful consideration and optimization of gsISP management in conjunction with ICI treatment.