Can Ipilimumab restore immune response in advanced NSCLC after progression on anti-PD-1/PD-L1 agents?

Anti-PD-1/PD-L1 agents play a crucial part in the treatment of non-small cell cancer (NSCLC) demonstrating improved overall response rate (ORR) and overall survival (OS). Recent studies evaluating combination treatment with anti-PD-1 and anti-CTLA-4 suggests improved outcome but also increased toxicity. Evidence is scarce regarding subsequent treatment with immune checkpoint inhibitors (ICPI) after progression on anti-PD-1/PD-L1. A total of 15 patients were treated with a combination of anti-PD1 agent and ipilimumab after confirmed progression of disease on anti-PD1/PDL1 alone during 2017. Clinical data were retrieved retrospectively. Disease control rate (DCR) was defined as partial response (PR) or stable disease (SD). The overall DCR was 33.3% (n= 5); two patients with PR and three patients with SD, three of whom had prior documented disease control on anti-PD1. The immune-related adverse event (irAE) rate was 40% (n= 6); two patients had grade 3 AE and one patient died of pneumonitis. While the median time to progression was two months (range 0.5-16), four of the five patients with PR/SD experienced durable benefit for 8-16 months. This small retrospective cohort of heavily pretreated unselected patients suggests ipilimumab might reboost the immune response in patients with advanced NSCLC following progression of disease on anti-PD1 therapy, while delaying exposure to the higher toxicity rates associated with upfront combination therapy. This strategy should be explored prospectively.