CTIM-28. NEOADJUVANT ANTI-PD1 IMMUNOTHERAPY FOR SURGICALLY ACCESSIBLE RECURRENT GLIOBLASTOMA: CLINICAL AND MOLECULAR OUTCOMES OF A STAGE 2 SINGLE-ARM EXPANSION COHORT
Abstract 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.
Authors
- G. Rees Cosgrove (ORCID: https://orcid.org/0000-0002-6220-5752)
- Lisa Doherty
- Keith Lloyd Ligon (ORCID: https://orcid.org/0000-0002-7733-600X)
- Robert Michael Prins (ORCID: https://orcid.org/0000-0002-6282-6583)
- Pierpaolo Peruzzi (ORCID: https://orcid.org/0000-0001-5034-2963)
- Maria Lavallee
- Richard G. Everson (ORCID: https://orcid.org/0000-0003-2809-3061)
- Kathryn Partridge
- Patrick Y. Wen (ORCID: https://orcid.org/0000-0002-0774-7700)
- Gilbert Youssef (ORCID: https://orcid.org/0000-0001-6109-7692)
- J Ricardo McFaline-Figueroa (ORCID: https://orcid.org/0000-0002-6670-1841)
- Eudocia Q. Lee (ORCID: https://orcid.org/0000-0003-3355-5179)
- Rameen Beroukhim (ORCID: https://orcid.org/0000-0001-6303-3609)
- Omar Arnaout (ORCID: https://orcid.org/0000-0003-3890-8615)
- Wenya Linda Bi (ORCID: https://orcid.org/0000-0002-4635-0247)
- Corey LaForest-Roys
- Ingy Romany (ORCID: https://orcid.org/0000-0003-0492-7893)
- Jennifer Clarke (ORCID: https://orcid.org/0000-0002-8054-7342)
- Anna Smokovich
- Ugonma Nnenna Chukwueke (ORCID: https://orcid.org/0000-0003-0598-9535)
- Alyssa Russ (ORCID: https://orcid.org/0000-0002-6353-139X)
- E. Antonio Chiocca
- David A. Reardon (ORCID: https://orcid.org/0000-0001-6674-0157)
- Alexa Myers
- Timothy F. Cloughesy (ORCID: https://orcid.org/0000-0002-8656-7483)
- Raymond Y. Huang (ORCID: https://orcid.org/0000-0001-7661-797X)
- Tracy T. Batchelor (ORCID: https://orcid.org/0000-0001-7568-6607)
- Lakshmi Nayak
- Amanda Spearman
- Jennifer Stefanik
- Gang Li (ORCID: https://orcid.org/0000-0002-4753-9420)
- Lu Sun (ORCID: https://orcid.org/0000-0002-6592-1156)
- Jiyoon Kim (ORCID: https://orcid.org/0000-0002-9816-5940)
- Catharina Westergaard
- Christine McCluskey (ORCID: https://orcid.org/0000-0001-5610-8115)
- Rachel Garcia Fox
Institutions
- Brigham and Women's Hospital (US)
- University of California, Los Angeles (US)
- University of California, San Francisco (US)
- NYU Langone Health (US)
- Massachusetts General Hospital (US)
- Dana-Farber Cancer Institute (US)
Publication Details
- Journal
- Neuro-Oncology
- Published
- 2024-11-01
- DOI
- https://doi.org/10.1093/neuonc/noae165.0361
- Primary Topic
- Glioma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00