CTIM-17. INDIVIDUALIZED MULTIMODAL IMMUNOTHERAPY (IMI) FOR ADULTS WITH DIFFUSE MIDLINE GLIOMA OR DIFFUSE HEMISPHERIC GLIOMA

Abstract Diffuse Midline Glioma (DMG, H3K27 mutant) and Diffuse Hemispheric Glioma (DHG, H3G34 mutant) are rare malignant CNS tumors with dismal prognosis. We retrospectively searched in our database for adults (>18y) with molecularly define DMG/DHG, treated between May 2015 and 2024 with IMI as part of first-line treatment. Amongst 157 IMI-treated malignant glioma patients, four patients fit these restrictions, pointing to scarce experience of IMI for DMG/DHG adult patients. HM (M, 29y) was diagnosed with a DMG in the pons. He received radiochemotherapy, and continued after 2x TMZm with BRAF-MEK-inhibition therapy. He received one IO-Vac® dendritic cell vaccine but showed fast progression thereafter. He died 9 months after diagnosis. GJE (F, 28y) had a DMG at the corpus callosum. She received radiochemotherapy and 6x TMZm, followed by 2x IO-Vac® and 3x maintenance immunogenic cell death (ICD) immunotherapy (NDV injections, sessions of modulated electrohyperthermia), combined with WT1 and H3K27M long-peptide vaccines. She progressed after 20 months, for which a new IO-Vac® and an H3K27M short- and long-peptide vaccine were given. She died 5 months later. Overall Survival (OS) was 26 months after initial diagnosis. JD (F, 27y) was diagnosed with a DMG in C2-C6. She received radiochemotherapy followed by IMI alone, including 2x IO-Vac®, one ICD immunotherapy, and four doses of anti-PD1. She died 17 months later, making OS 27 months after diagnosis. VJ (F, 21y) had a DHG in the left cerebrum. She received radiochemotherapy and 12 cycles of maintenance TMZ (TMZm), between which ICD immunotherapy was inserted each time. Afterwards, she received two IO-Vac®. Finally, she received ICD immunotherapy (6x) combined with checkpoint inhibitors (4x anti-CTLA4, 10x anti-PD1). Thirty months after diagnosis, she is in remission with a stable Health Utility Index of 0.72. IMI might have contributed to a better OS in three out of four DMG/DHG patients, and should be explored further as part of the treatment for these patients.