Bavituximab Decreases Immunosuppressive Myeloid-Derived Suppressor Cells in Newly Diagnosed Glioblastoma Patients

• Published in: Clinical cancer research 2023-08, Vol.29 (16), p.3017-3025
• Main Authors: Ly, K Ina, Richardson, Leland G, Liu, Mofei, Muzikansky, Alona, Cardona, Jonathan, Lou, Kevin, Beers, Andrew L, Chang, Ken, Brown, James M, Ma, Xiaoyue, Reardon, David A, Arrillaga-Romany, Isabel C, Forst, Deborah A, Jordan, Justin T, Lee, Eudocia Q, Dietrich, Jorg, Nayak, Lakshmi, Wen, Patrick Y, Chukwueke, Ugonma, Giobbie-Hurder, Anita, Choi, Bryan D, Batchelor, Tracy T, Kalpathy-Cramer, Jayashree, Curry, William T, Gerstner, Elizabeth R
• Format: Article
• Language: English
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-23-0203

We evaluated the efficacy of bavituximab-a mAb with anti-angiogenic and immunomodulatory properties-in newly diagnosed patients with glioblastoma (GBM) who also received radiotherapy and temozolomide. Perfusion MRI and myeloid-related gene transcription and inflammatory infiltrates in pre-and post-treatment tumor specimens were studied to evaluate on-target effects (NCT03139916). Thirty-three adults with IDH--wild-type GBM received 6 weeks of concurrent chemoradiotherapy, followed by 6 cycles of temozolomide (C1-C6). Bavituximab was given weekly, starting week 1 of chemoradiotherapy, for at least 18 weeks. The primary endpoint was proportion of patients alive at 12 months (OS-12). The null hypothesis would be rejected if OS-12 was ≥72%. Relative cerebral blood flow (rCBF) and vascular permeability (Ktrans) were calculated from perfusion MRIs. Peripheral blood mononuclear cells and tumor tissue were analyzed pre-treatment and at disease progression using RNA transcriptomics and multispectral immunofluorescence for myeloid-derived suppressor cells (MDSC) and macrophages. The study met its primary endpoint with an OS-12 of 73% (95% confidence interval, 59%-90%). Decreased pre-C1 rCBF (HR, 4.63; P = 0.029) and increased pre-C1 Ktrans were associated with improved overall survival (HR, 0.09; P = 0.005). Pre-treatment overexpression of myeloid-related genes in tumor tissue was associated with longer survival. Post-treatment tumor specimens contained fewer immunosuppressive MDSCs (P = 0.01). Bavituximab has activity in newly diagnosed GBM and resulted in on-target depletion of intratumoral immunosuppressive MDSCs. Elevated pre-treatment expression of myeloid-related transcripts in GBM may predict response to bavituximab.