PDCT-15. MULTIMODAL IMMUNOTHERAPY AS PART OF MULTIMODAL TREATMENT FOR DIPG

Because some tumor antigens in DIPG are defined, the immune system might provide long-term tumor control via memory T cell activity. Our concept consists of induction of intratumoral immunogenic cell death through infusion of Newcastle Disease Virus (NDV) together with local application of modulated electrohyperthermia (mEHT) and injections of autologous mature monocyte-derived dendritic cells (DCs) loaded with NDV/mEHT-induced serum-derived antigenic microparticles + NDV. Treatment is provided on individual basis. Data were retrospectively collected. 36 DIPG children with median age 5.5y (range 2-19y) were treated with immunotherapy, 24 of them as part of primary treatment (DIPGprim) and 12 at time of progressive disease after first line treatment (DIPGprog). 81% of DIPGprim children had a Lansky score >70. At start of immunotherapy, 33% of patients had deficient IFN-g expression in the CD4+ T cells. Diminished NK function was observed in 75%. The repetitive NDV infusions, the modulated electrohyperthermia and the production and administration of the DCs all were feasible. No major toxicity was observed. We detected the increase of GBM antigen cross-reacting IFN-g-producing T cells in those patients that could be immunomonitored. Data were fixed at 04/04/2017. Median PFS was 8.36m. Rescue after progression was mainly re-irradiation. Median OS was 14.23 months. 18m OS was estimated as 35% (asymmetrical 95%CI: +25.68, -24.25). Median OS of the 10 DIPGprog children calculated from last event prior to immunotherapy was 5.96m. These clinical experiences support the concept that immunotherapy can be considered as part of multimodal treatment for patients with DIPG at an early stage of their disease. Its effect is likely located at an improvement of long-term OS. The latter read-out, together with the individualized treatment approach, makes the scientific steps towards evidence-based efficacy demonstration very challenging.