Pooled analysis of impact of corticosteroids for immune-related adverse events on efficacy of immune checkpoint inhibitors

Retrospective studies suggest that immunosuppressive treatment of immune-related adverse events (irAEs) impairs survival in melanoma patients receiving immune checkpoint inhibitors (ICIs). Pooled analysis of six CheckMate trials (067, 142, 214, 648, 743, and 9LA) investigated the impact of immunosuppression for irAEs on efficacy of ICIs for other tumor types. Among 1959 patients in the trials, 834 patients received immunosuppression (832 corticosteroids, 81 second-line immunosuppressants). High corticosteroid peak dose was associated with worse progression-free survival: aHR 1.15 (95% CI 1.02-1.29) for 1.0 versus 0.5 mg/kg prednisolon and 1.43 (1.05-1.96) for 2.0 versus 0.5 mg/kg prednisolone. Similar associations were seen for overall survival. Cumulative corticosteroid dose was not associated with survival. Use of second-line immunosuppression was not significantly associated with PFS or OS. The authors conclude that higher corticosteroid peak dose, but not cumulative dose, was associated with worse survival outcomes among patients who have irAEs from ICIs for various tumor types.