The exploratory endpoint for our prospective single-arm study (NCT 03347617) evaluated longitudinal changes in immune cell sub-populations (B-cells, T-cells, NK cells, monocytes, and myeloid cells) in 25 newly diagnosed glioblastoma patients who received standard of care chemoradiation with concurrent pembrolizumab after maximal safe resection. Patient demographics included the following: 15 males, 10 females, age range 25-72 years old, mean age 52 years old, 8 MGMT unmethylated, 17 MGMT methylated, 7 IDH1 mutant, and 18 IDH1 wild-type. 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 survival analysis using Cox proportional hazards regression in R. CD5+ CD19+ B-cell count was significantly associated with progression-free survival at pre-treatment (hazard ratio (HR)= 0.76; likelihood ratio test (LRT) p=0.029) and post-radiation (HR = 0.16; LRT p=0.004) timepoints. No association with progression-free survival was found in 25 other immune cell sub-populations evaluated. The study will continue to monitor for progression. Results of imaging, tissue histology, overall survival analysis and functional studies in animal models are pending. Investigations of the immunological mechanisms underlying the potential anti-tumor activity of CD5+ B-cells are ongoing and include detection and characterization of anti-tumor antibodies, T cell-dependence of the response, and whether it is triggered by pembrolizumab. Modulating CD5+ B-cells, or the antibodies they produce, may have therapeutic implications in improving checkpoint inhibition in glioblastoma.

Citation Format: Cheryl J. Claunch, Claire Diaz, Riley A. Roth-Carter, Lauren Popp, Rochelle Fu, Amy E. Huddleston, Dana L. Moussalli, Julie Peterson, Kutluay Uluc, Laszlo Szidonya, Guang Fan, Ferdinando Pucci, Ramon F. Barajas, Leslie L. Muldoon, Edward A. Neuwelt, Prakash Ambady. CD5+ B-cell count is a favorable prognostic factor associated with progression-free survival in glioblastoma patients receiving chemoradiation and pembrolizumab [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT183.