Abstract 6519: Dendritic cell vaccine cell numbers and survival in patients with primary glioblastoma

Abstract Standard glioblastoma (GBM) treatment is associated with poor survival. A promising novel immunotherapy consists of autologous dendritic cells (DC) pulsed with autologous tumor antigens (ATA) from a lysate of irradiated self-renewing autologous cancer cells. An open-label, phase 2 trial was conducted in 57 patients with primary GBM. Here we report correlations between survival and DC-ATA doses. Two autologous intermediate products were manufactured for each patient: a tumor cell line established from resected GBM, and DC differentiated from cryopreserved peripheral blood monocytes (MC). Patients were enrolled prior to standard radiation therapy (RT) and temozolomide (TMZ) chemotherapy. DC-ATA were manufactured during RT/TMZ, divided into individual doses, then cryopreserved in liquid nitrogen. For each patient-specific vaccine batch, cell numbers were calculated using a hemocytometer; viability was determined before cryopreservation (cryo) using trypan blue and post-cryo using 7ADD per flow cytometry. After RT/TMZ, up to 8 doses were injected s. c. concurrent with TMZ over 6 months. Patients were grouped into tertiles based on DC-ATA cell numbers and survival. Prism 10. 03 was used to generate survival curves and calculate correlation coefficients and log-rank and T-Test comparisons. As previously reported, cell line success rate was 71/73, sufficient MC numbers were collected by leukapheresis for 63/65; DC-ATA was successfully manufactured for 60/60; 57 patients were treated; median progression free survival (PFS) and overall survival (OS) were 10. 4 and 16. 0 months respectively. Correlations were strong between total and viable DC-ATA pre-cryo (0. 97, p0. 0001) and post-cryo (0. 95, p0. 0001), but weaker between DC-ATA pre- and post-cryo (0. 30, p=0. 02), and between viable DC-ATA pre- and post-cryo (0. 37, p=0. 004). When patients were grouped by OS tertiles, medians were 9. 8, 18. 1, and more than 36 months. There were no differences in the average millions (M) of DC-ATA pre-cryo (10. 0, 9. 7, 9. 6), viable DC-ATA pre-cryo (8. 5, 7. 8, 7. 9), DC-ATA post-cryo (9. 0, 10. 3, 10. 8) or viable DC-ATA post-cryo (6. 0, 7. 3, 7. 4). Similarly, when patients were grouped into tertiles by DC-ATA numbers, there were no differences in OS curves associated with DC-ATA pre-cryo, viable DC-ATA pre-cryo, DC-ATA post-cryo, or viable DC-ATA post-cryo. Pre-cryo viable DC-ATA numbers ranged from 0. 27 to 27. 0 M. An ineffective dose was not identified; pre-cryo viable DC-ATA doses of less than 2M were associated with OS of 10. 4, 13. 0, 13. 3, and 36. 4+ months. Also, there was no OS difference by number of MC used to manufacture DC or by number of DC manufactured. In conclusion, there was no evidence for a dose/response relationship between DC-ATA dose and OS for any of the parameters tested. This data supports that pre-cryo cell counts can be used to establish treatment doses. Pre-cryo viable cell counts of 2M DC-ATA per dose seem sufficient. Citation Format: Robert O. Dillman, Gabriel I. Nistor, Krystal Godding, Rockelle Robles, Hans S. Keirstead. Dendritic cell vaccine cell numbers and survival in patients with primary glioblastoma abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 6519.