CTIM-33. IMMUNE BIOMARKERS OF TREATMENT RELATED IMAGING CHANGES IN GLIOBLASTOMA PATIENTS TREATED WITH STANDARD OF CARE PLUS PEMBROLIZUMAB

Abstract Pseudoprogression is a post-treatment imaging phenomenon in glioblastoma (GBM) that mimics true progression. Immune checkpoint inhibition with pembrolizumab has shown clinical benefits in multiple cancers and is a burgeoning treatment in GBM. Discerning pseudoprogression, or treatment-related imaging changes, from true progression is essential for appropriate treatment recommendations. However, there are no reliable biomarkers that can differentiate between pseudoprogression and true progression. Our prospective single-arm study (NCT 03347617) evaluated immune cell sub-populations (B-cells, T-cells, NK cells, monocytes, and myeloid cells) in newly diagnosed GBM patients who received standard-of-care chemoradiation plus concurrent pembrolizumab after maximal safe resection. Flow cytometry was performed on blood collected at predetermined timepoints (pre-treatment, post-radiation, suspected progression, and confirmed progression) and immune cell sub-populations were evaluated as covariates in univariable and multivariable logistic regression analysis. Of the 56 patients enrolled in this trial, 51 completed blood collection. Median survival was 13.84 months. Fifteen (29%) patients had pseudoprogression by modified RANO criteria and 36 (70.5%) had suspected or confirmed progression. Univariable analysis identified the following serum derived immune populations as being significantly associated with pseudoprogression: cytotoxic T-cell percentage (CD3+CD8+; HR: 1.10; p=0.045); total NK Cells percentage (CD3+CD56+; HR:0.912; p=0.0.053); IGD+CD27-naïve B-cells of B-cell percentage (HR: 0.976; p=0.014); IGD+CD27+non-switched B of B-cell percentage (HR:1.07; p=0.036). Backward selection multivariable logistic regression analysis confirmed the significant association of cytotoxic T-cell percentage (CD3+CD8+; HR:1.02; p=0.049) with pseudoprogression while controlling for IGD+CD27+non-switched B of B-cell percentage (HR:1.01, p=0.116). Increasing levels of serum cytotoxic T-cells in GBM patients treated with standard-of-care plus pembrolizumab is associated with pseudoprogression and may be used to differentiate between true progression. Validation of results is needed in a control population treated with standard-of-care prior to clinical implementation. Future studies will utilize serum immune biomarkers coupled with radiomic features to better characterize the pseudoprogression signature in GBM.