Dendritic Cell Vaccine Boosts Survival in Glioblastoma
Overall survival was 72% at 12 months but dropped to 54% at 14.6 months.
AV-GBM-1, an autologous, dendritic cell (DC) vaccine, was well-tolerated and increased progression-free survival (PFS) in patients with newly diagnosed glioblastoma (GBM) in a phase 2 trial (NCT03400917).
Data from the study were presented at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), November 10-14, 2021 by first author Daniela A. Bota, MD, PhD, vice dean, clinical research, medical director, Center for Clinical Research and Neuro-Oncology Program, and director, Alpha Stem Cell Clinic, Sue and Bill Gross Stem Cell Research Center, UC Irvine.
Bota and colleagues wrote that “standard therapy of GBM, which includes maximum safe resection, concurrent radiation therapy and temozolomide (RT/TMZ) chemotherapy followed by maintenance TMZ, is associated with poor overall survival (OS). Adding treatment with AV-GBM-1, a vaccine consisting of autologous DC pulsed with autologous tumor antigens (ATA) may improve OS. A multi-center phase II clinical trial was conducted to determine feasibility, safety, and efficacy of AV-GBM-1.”
The trial enrolled patients with primary GBM, a successful GBM cell culture, sufficient monocyte collection by leukapharesis, Karnofsky Performance status of 70 or greater, and a plan to treat with concurrent RT/TMZ. Mast cells (MCs) were differentiated into DCs via interleukin-4 and granulocyte-macrophage colony stimulating factor (GM-CSF). The study primarily assessed if OS was at least 75% 14.6 months after intent-to-treat (ITT) enrollment. Secondary outcome measures included PFS from ITT enrollment and from first injection.
Amine transaminases from the lysate of irradiated GBM cells are used to incubate autologous DCs to create AV-GBM-1. Promoting factors for stem cell and progenitor cell survival and proliferation were used in serum-free media.
During the study, patients received up to 8 subcutaneous injections of AV-GBM-1 admixed with 500 μg GM-CSF after recovery from RT/TMZ. Patients were followed-up for a minimum of 15.2 months.
Investigators found that cell cultures and monocyte collections each had a 97% success rate. The cell vaccine was manufactured for all 60 patients enrolled. Overall, 392 injections were administered to 57 patients and 68% of patients received all 8 injections. Adverse events (AEs) included local injection site reactions (16%) and flu-like symptoms (10%).
Preliminary efficacy analyses revealed that PFS from ITT enrollment is 10.3 months, which is around 50% longer than comparable standard therapy arms in 4 other randomized trials. PFS from first injection is 8.3 months, which if 51% and 107% longer than comparable standard therapy arms in 2 other randomized trials. The median OS is 16.0 months – OS was 72% at 12 months but dropped to 54% at 14.6 months.
“Patent-specific AV-GBM-1 was reliably manufactured and distributed for administration. AV-GBM-1 produced minimal toxicity. PFS was very encouraging but did not translate into OS, perhaps because of discontinuation of treatment after 8 months,” Bota and colleagues concluded.
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