DDDR-12. Impact of clinical and molecular factors on pembrolizumab response in IDH-wildtype glioblastoma

Abstract INTRODUCTION Glioblastoma multiforme (GBM), the most aggressive primary CNS malignancy, is characterized by high mortality, treatment resistance, and recurrence. Immunotherapies such as PD-1 inhibitor pembrolizumab, a successful intervention in various cancers, remain inefficacious in treating GBM. Clinical factors such as patient demographics, biomarkers, and co-administration with immunomodulating medications such as corticosteroids or selective serotonin reuptake inhibitors (SSRIs) have yet to be evaluated as determinants in pembrolizumab responsiveness. Objective: To delineate the impact of clinical factors on survival and recurrence to inform individualized treatment plans for IDH-wildtype GBM patients treated with pembrolizumab. METHODS 57 pembrolizumab-treated GBM patients at UCLA Medical Center were retrospectively studied. Biomarkers, baseline characteristics, GBM progression, and medication history were reviewed. Kaplan-Meier and Cox regression analyses assessed the prognostic value of each variable. RESULTS All patients received corticosteroids; steroid use within 30 days of resection did not impact survival on univariate analysis (p = 0.6648 for PFS, p = 0.9697 for OS), however adjusting for confounding factors revealed a significant effect on OS (HR = 0.14; 95%CI, 0.019–0.935). SSRI use was associated with a non-significant improved PFS (p = 0.0928) but did not affect OS (p = 0.3382). Patients with 1 or 2 recurrences trended towards improved OS (p = 0.1529, HR = 0.10), warranting investigation into the impact of 1 versus 2 recurrences. Although age did not significantly impact survival (p = 0.9869 for PFS, p = 0.4879 for OS), females displayed improved PFS (p <0.05) and trended towards improved OS (p = 0.136). MGMT methylation correlates with significantly lowered OS (HR = 0.12; 95%CI, 0.018–0.648). CONCLUSION Key clinical factors when considering treatment with pembrolizumab are recurrence, MGMT methylation, and gender, with the impact of steroids needing to be further explored. SSRIs do not demonstrate significant impact for this population.