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BACKGROUND Patients with diffuse midline gliomas (DMG), including diffuse intrinsic pontine glioma (DIPG), have dismal outcomes. We previously described the H3.3K27M mutation as a shared neoantigen in HLA-A*02.01+ H3.3K27M+ DMGs. Within the Pacific Pediatric Neuro-Oncology Consortium, we assessed the safety and efficacy of an H3.3K27M-targeted peptide vaccine. PATIENTS AND METHODS Newly diagnosed patients aged 3–21 years with positive HLA-A*02.01+ and H3.3K27M+ status were enrolled into two strata after completion of radiation therapy: Stratum A for DIPG (n=19); Stratum B for non-pontine DMG (n=10). Vaccine was administered in combination with poly-ICLC every three weeks for eight cycles, followed by once every six weeks. Immunological responses were assessed in peripheral blood mononuclear cells using mass cytometry. RESULTS 19 patients enrolled in Stratum A (median age=11 years) and 10 in Stratum B (median age=13 years). There were no grade 4 treatment-related adverse events (TRAE). Injection site reaction was the most commonly reported TRAE. Overall survival (OS) at 12 months was 40% (95% CI, 22% to 73%) for Stratum A and 39% (95% CI, 16% to 93%) for Stratum B. The median OS was 16.1 months in patients exhibiting an expansion of H3.3K27M-reactive CD8+ T-cells compared to 9.8 months for their counterparts (p=0.05). DIPG patients with below-median baseline levels of myeloid-derived suppressor cells had prolonged OS compared to their counterparts (p&amp;lt; 0.1). Immediate pre-treatment dexamethasone administration inversely associated with H3.3K27M-reactive CD8+ T-cell responses. However, neither tumor size or bulk CD8+ T-cell status was significantly associated with OS. CONCLUSION Administration of the H3.3K27M-specific vaccine is well tolerated. Patients with H3.3K27M-specific CD8+ immunological responses demonstrated prolonged OS compared to non-responders.

neuro-oncology

DDRE-10. IMMUNE PROFILES ASSOCIATE WITH OUTCOMES IN HLA-A*02:01+, H3.3K27M+ PATIENTS WITH DIFFUSE MIDLINE GLIOMAS TREATED WITH H3.3K27M PEPTIDE VACCINE COMBINED WITH POLY-ICLC: A PNOC REPORT