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. (9th November 2020)

• Record Type: Journal Article
• Authors: Mueller, Sabine; Taitt, Jared M; Villanueva-Meyer, Javier; Bonner, Erin R; Nejo, Takahide; Lulla, Rishi R; Goldman, Stewart; Banerjee, Anurhada; Chi, Susan; Whipple, Nicholas S; Crawford, John R; Gauvain, Karen; Nazemi, Kellie; Watchmaker, Payal; Almeida, Neil D; Okada, Kaori; Salazar, Andres; Gilbert, Ryan; Nazarian, Javad; Molinaro, Annette; Butterfield, Lisa H; Prados, Michael; Okada, Hideho
• Is Part Of: Neuro-oncology. Volume 22(2020)Supplement 2
• Page Start: ii63
• Page End: ii63
• Publication Date: 2020-11-09
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noaa215.255
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: 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< 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.