CTIM-28. NEOADJUVANT ANTI-PD1 IMMUNOTHERAPY FOR SURGICALLY ACCESSIBLE RECURRENT GLIOBLASTOMA: CLINICAL AND MOLECULAR OUTCOMES OF A STAGE 2 SINGLE-ARM EXPANSION COHORT
J Ricardo McFaline-Figueroa, Lu Sun, Gilbert Youssef, Raymond Huang, Gang Li, Jiyoon Kim, Eudocia Lee, Lakshmi Nayak, Ugonma Chukwueke, Rameen Beroukhim, Tracy Batchelor, E Antonio Chiocca, Richard Everson, Lisa Doherty, Jennifer Stefanik, Kathryn Partridge, Amanda Spearman, Alexa Myers, Catharina Westergaard, Alyssa Russ, Maria Lavallee, Anna Smokovich, Corey LaForest-Roys, Rachel Garcia Fox, Christine McCluskey, Wenya Linda Bi, Omar Arnaout, PierPaolo Peruzzi, G Rees Cosgrove, Keith Ligon, Isabel Arrillaga Romany, Jennifer Clarke, David Reardon, Timothy Cloughesy, Robert Prins, Patrick WenAbstract
Glioblastoma is immunologically “cold” and resistant to single-agent immune-checkpoint inhibitors (ICI). Our previous study of neoadjuvant pembrolizumab in surgically-accessible recurrent glioblastoma identified a molecular signature of response to ICI and suggested that neoadjuvant pembrolizumab may improve survival. To increase the power of this observation, we performed bulk-RNA seq on resected tumor tissue from an additional 25 patients with recurrent glioblastoma treated with neoadjuvant pembrolizumab. Neoadjuvant pembrolizumab was associated with suppression of cell cycle/cancer proliferation genes and upregulation of T-cell/interferon-related gene expression. This signature was unique to patients treated with neoadjuvant pembrolizumab and was an independent positive risk factor for survival. PF6 for the stage 2 expansion cohort was 0%, while overall survival and progression-free survival were similar to historical controls at 6.8 months and 2.5 months, respectively. Our results demonstrate a clear pharmacodynamic effect of anti-PD1 therapy in glioblastoma and identify pathways that may mediate resistance. However, we did not observe a survival benefit to neoadjuvant pembrolizumab in recurrent glioblastoma in our expansion cohort. Our new data suggests some patients may exhibit innate resistance to pre-surgical ICI and require other concomitant therapies to sensitize effectively.