Work

Atim-16. Validation of Response to Neoadjuvant Anti-pd-1 Immunotherapy in Recurrent Glioblastoma

Year: 2019

Type: article

Abstract: BACKGROUND Recurrent glioblastoma has a poor median overall survival despite multimodal treatment. The use of pembrolizumab, an anti-PD-1 monoclonal antibody, demonstrates promise, including improved overall survival and increased immune response, when used in the neoadjuvant setting. METHODS We evaluated 13 patients with surgically accessible recurrent glioblastoma who were treated at the University of California, Los Angeles with neoadjuvant checkpoint inhibition prior to tumor resection. Combining data with our previously published multi-center study, we followed this cohort prospectively, performing tumor gene expression to validate the immune response and improved survival following neoadjuvant therapy with pembrolizumab. RESULTS When combined with findings from our prior study, patients in the neoadjuvant group (n = 27) had an overall survival of 400 days, whereas those in the adjuvant-only group (n = 19) had a median overall survival of 228 days by Kaplan-Meier estimator (P = 0.029, log-rank test). Progression-free survival in the neoadjuvant group was 108 days, whereas in the adjuvant-only group it was 72.5 days (P = 0.017, log-rank test). In elastic net penalized Cox proportional hazards regression, neoadjuvant anti-PD-1 blockade continued to be associated with improved overall survival, with a hazard ratio of 0.11 (P=0.003, log-rank test). Bulk tumor gene expression corroborates our previously described pattern of increased T-cell- and IFN-g-related gene expression, decreased cell-cycle-related signatures and their association with clinical response. Additionally, epigenetic regulation inversely correlated with clinical response. CONCLUSIONS Our findings support the neoadjuvant timing of PD-1 blockade in enhancing local immune responses and prolonging overall- and progression-free-survival. Correlative biological studies suggest a potential role for cell-cycle-related gene expression as a biomarker to predict response to therapy. Continued data collection and the addition of patients to the neoadjuvant arm of the trial, will be crucial to determine the potential role of checkpoint inhibition in the treatment of this deadly disease.

Source: Neuro-Oncology

DOI: 10.1093/neuonc/noz175.016