Immu-12. Standard of Care Plus Individualized Multimodal Immunotherapy (Imi) to Treat H3.3g34 Diffuse Midline Glioma

Abstract BACKGROUND The prognosis of patients with H3.3G34 diffuse midline glioma is uniformly dismal. Since approval of IO-Vac® as advanced therapy medicinal product (27/05/2015), we treated two young patients with IMI in connection to the standard of care. METHODS BN (male 14y, diagnosis 01/2022) and JV (female 21y, diagnosis 12/2021) received partial resection resp. biopsy. Both underwent standard radiochemotherapy. RESULTS BN received 3/6 TMZ/Lomustin maintenance chemotherapy before start IMI. JV started with 1/12 TMZ courses together with IMI. Five-day immunogenic cell death (ICD) immunotherapy (Newcastle Disease Virus bolus injections and local modulated electrohyperthermia) were added to each maintenance chemotherapy block. After maintenance chemotherapy plus ICD immunotherapy, both received active-specific immunotherapy with two IO-Vac® vaccinations (autologous mature dendritic cells loaded with ICD-induced antigenic extracellular microvesicles). Both started with modulatory immunotherapy (4x ipilimumab/nivolumab q3w and further 6x nivolumab q4w) in combination with maintenance ICD immunotherapy. BN had a spinal relapse 19 months after initial diagnosis. He restarted with local radiotherapy and thereafter Lomustin plus Nivolumab, ultimately stopped due to arthritis. He died 24 months after diagnosis. Because of the observation of spreading disease, JV is now further treated with maintenance ICD immunotherapy using local modulated electrohyperthermia to the brain and to the upper and lower spine. She shows no evidence of progressive disease after 25 months. CONCLUSIONS The addition of IMI to standard of care for young patients with H3.3G34 diffuse midline glioma might give a glimpse of hope, and further anecdotal experiences should be collected. Additional treatment of the spinal axis with modulated electrohyperthermia might be required for patients with DMG.