Bavituximab decreases immunosuppressive myeloid-derived suppressor cells in newly diagnosed glioblastoma patients.

Abstract

We evaluated the efficacy of bavituximab - a monoclonal antibody with anti-angiogenic and immunomodulatory properties - in newly diagnosed glioblastoma (GBM) patients who also received radiation 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 isocitrate-dehydrogenase-wild-type GBM received 6 weeks of concurrent chemoradiation, followed by 6 cycles of temozolomide (C1-C6). Bavituximab was given weekly, starting week 1 of chemoradiation, 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 (PBMCs) and tumor tissue were analyzed pre-treatment and at disease progression using RNA transcriptomics and multispectral immunofluorescence for myeloid-derived suppressor cells (MDSCs) and macrophages. The study met its primary endpoint with an OS-12 of 73% (95% CI 59-90%). Decreased pre-C1 rCBF (HR 4.63, p=0.029) and increased pre-C1 Ktrans were associated with improved OS (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.