Clinical response to ipilimumab: Effect of systemic corticosteroids used to manage immune-related adverse events (irAEs)

Background: Ipilimumab (IPI), a fully human monoclonal antibody, potentiates antitumor T-cell responses by blocking cytotoxic T-lymphocyte antigen-4. IPI is the first agent to demonstrate improvement in OS in previously-treated patients (PTS) with advanced melanoma in a phase 3 trial (MDX010-20). IrAEs, reflective of IPI mechanism of action, are the most common AEs and are generally manageable with corticosteroids. The objective of this post hoc analysis was to assess the impact of corticosteroid use on IPI clinical activity. Methods: 676 HLA-A∗0201+ pts were randomized (3:1:1) to IPI 3 mg/kg + a gp100 peptide vaccine (n=403), IPI alone (n=137) or gp100 alone (n=136). Induction dosing was with IPI 3 mg/kg every 3 weeks (wks) for 4 doses. Investigator-evaluated tumor assessments were at baseline, Wks 12, 16, 24, and every 3 months thereafter, using modified World Health Organization criteria. Pts were analyzed in two groups according to whether they received steroids or not. Two retrospective analyses were performed: one to assess clinical activity (complete or partial response (CR, PR) or stable disease (SD) not followed by progressive disease (PD)) in the presence or absence of steroids, and one to assess the impact of steroid administration on maintaining clinical response. Results: The clinical benefit rate was similar regardless of whether pts received prior corticosteroids (Table). Of pts in the IPI alone group who developed a response (CR, PR), 2/8 who received steroids after response demonstrated disease progression compared to 3/7 who did not receive steroids after response. In the IPI + gp100 group, disease progression was observed in 0/1 pts who received steroids post-response compared with 12/22 of those who did not. Conclusions: The development of clinical activity or maintenance of clinical response following IPI treatment was similar with or without the use of systemic corticosteroids.