Description
Prednisone at immunosuppressive doses may blunt pembrolizumab's anti-tumour efficacy by dampening the T-cell responses required for checkpoint inhibitor activity.
Mécanisme
Corticosteroids suppress T-cell proliferation, cytokine secretion, and effector function through glucocorticoid receptor-mediated gene regulation; this directly antagonises the mechanism by which pembrolizumab augments anti-tumour immunity.
Signification clinique
Retrospective studies and meta-analyses indicate decreased pembrolizumab efficacy (lower ORR, shorter PFS) in patients who require corticosteroid doses equivalent to >10 mg prednisone/day at the time of anti-PD-1 initiation.
Prise en charge
Avoid prophylactic or elective corticosteroid use with pembrolizumab; when steroids are required for irAEs or other indications, use the lowest effective dose and taper as rapidly as clinically safe.