INNV-18 - Multiphase combined treatment, including individualized multimodal immunotherapy for adults with GBM: single institute real world medical data in the light of clinical trial research data

A phase III prospective externally controlled cohort trial recently demonstrated beneficial effects of DCVax®-L for adults with GBM. The beneficial effect of TTF was demonstrated in a RCT. We designed a multiphase combined treatment using subsequentially 1/ modulated electrohyperthermia and Newcastle Disease Virus therapy to induce immunogenic cell death (ICD) during temozolomide maintenance chemotherapy, 2/ two autologous DC vaccinations (IO-Vac®), and 3/ ICD immunotherapy, long-peptide vaccines and one boost IO-Vac® vaccine. During phase 2+3, individualized modulatory immunotherapy was provided. Fifty adults with first-line IDH1wt GBM were retrospectively analysed: MGMT promoter-unmethylated (unmeth, 10 f, 18 m); -methylated (meth, 12 f, 10 m). Median age was 48y, median Karnofsky performance index was 80. More than half of the patients had less than complete resection. Dynamics in tumor biology and immune response were demonstrated during treatment (e.g. mRNA expression for PDL1 in circulating tumor cells), and required treatment adaptations (checkpoint inhibitors). The median OS of unmeth and meth patients were 22m (2y-OS: 42%) resp. 38m (2y-OS: 81%, p=0.0414). There were no considerable treatment-related adverse reactions. The (external) control arms in the DCVax®-L and TTF trials, which reflect the current standard-of-care clinical results, showed median OS and 2y-OS of 15m/21% in unmeth and 21m/42% in meth patients. TTF improved the OS in both unmeth and meth patients (17m/27% and 32m/59%), while DCvax®-L improved OS only in meth patients (15m/19% and 30m/58%). These real world data support to prospectively explore the addition of individualized multimodal immunotherapy during and after standard of care, and the role of treatment adaptations during treatment.