Use of immunotherapy in the complex treatment of glioblastomas: long-term results of a single-center prospective cohort study

Introduction. Glioblastoma is the most common primary malignant brain tumor with an aggressive course. Despite two decades of relentless search for new therapeutic approaches in the treatment of glioblastomas, there has been limited progress in improving patient survival outcomes. Numerous obstacles hinder the effective treatment of these patients, including the immunosuppressive tumor microenvironment, the blood-brain barrier, and extensive tumor heterogeneity. Despite these challenges, immunotherapy is emerging as a promising avenue that may provide new hope for the treatment of this malignancy.
Objective. To evaluate the efficacy and long-term results of using a dendritic cell vaccine in patients with brain glioblastomas, in comparison with the results of treatment of patients who did not receive immunotherapy.
Material and methods. A single-center, prospective, cohort study included 100 patients with a pathologically established diagnosis of glioblastoma, of different sexes and ages. The main group included 50 patients, in whose treatment, in addition to the standard (surgical treatment, radiation therapy and chemotherapy), antitumor immunotherapy with a dendritic cell vaccine was used. The comparison group also included 50 patients with standard treatment, but without immunotherapy. The vaccine was manufactured at the immunology laboratory and the substrate for its preparation was the tissue of the glioblastoma tumor of a specific patient and his blood. The vaccine was administered intradermally, paravertebrally. Subsequently, overall and relapse-free survival, as well as the immunological status of the patient were assessed according to laboratory blood tests.
Results. The median overall survival (OS) in the immunotherapy group was 21.3 months (95 % CI 4–37 months), in the group without immunotherapy it was 15.8 months (95 % CI 3–22 months) (p = 0.002). Free progression survival (FPS) in patients in the immunotherapy group was 13.1 months (95 % CI 1–20 months). In patients in the group without immunotherapy it was 7.9 months (95 % CI 1–12 months) (p = 0.003). Overall survival in patients who received three or more courses of immunotherapy was statistically significantly higher than in patients in the group who received 1 or 2 courses. When studying the level of 6 cytokines (IL-6, IL-8, IL-10, TNF-α, IFN-α, IFN-γ) in venous blood during the immunotherapy courses, a change in the average level of 4 cytokines (IL-6, IL-8, IL-10, TNF-α) above the initial average values was noted. The population of immune cells temporarily increased, and this increase coincided with 3 courses of immunotherapy during the observation period.
Conclusion. Overall, in our study, the clinical use of immunotherapy in the structure of complex treatment in patients with glioblastoma demonstrated a measurable immunological response. An increase in the median overall and free progression survival was also noted in patients of the study group and the comparison group. Data were also obtained that the number of courses of immunotherapy affects life expectancy. Further study of the possibilities of immunotherapy will allow this method to be included in the standards of complex treatment of patients with glioblastoma.

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