Vaccine-Chemotherapy Combination in Glioblastoma
John H. Sampson, MD, PhD, MBA, MHSc
Duane A. Mitchell, MD, PhD
Despite highly aggressive therapy that includes maximal tumor resection, high-dose radiation, and temozolomide chemotherapy, the prognosis for patients with newly diagnosed glioblastoma is dismal, with a median survival of less than 15 months, prompting researchers to study novel approaches to treat this cancer. Now, a small phase I study of 11 newly diagnosed patients with glioblastoma who received a vaccine targeting cytomegalovirus antigen pp65 combined with high-dose temozolomide chemotherapy found the therapy improved both progression-free and overall survival in these patients.
The study’s overall results strengthen prior findings targeting cytomegalovirus and provide evidence of the association between pp65 targeting in glioblastoma and long-term survival. The study by Batich et al was published in Clinical Cancer Research. John H. Sampson, MD, PhD, MBA, MHSc, of Duke University Medical Center, and Duane A. Mitchell, MD, PhD, of the University of Florida, are the corresponding authors of this study.
Eligibility criteria for this study included adults with a histologically confirmed, newly diagnosed World Health Organization grade IV glioblastoma. Following the standard of care, 11 patients, with a median age of 55 years, with newly diagnosed glioblastoma received dose-intensified temozolomide, at 100 mg/m2/d × 21 days per cycle, with at least 3 vaccines of pp65 lysosome–associated membrane glycoprotein mRNA-pulsed dendritic cells admixed with granulocyte macrophage colony-stimulating factor on day 23 ± 1 of each cycle. Thereafter, monthly dose-intensified temozolomide cycles and pp65 dendritic cells were continued if the patients had not progressed.
Following dose-intensified temozolomide cycle 1 and 3 doses of pp65 dendritic cells, pp65 cellular responses significantly increased. After dose-intensified temozolomide, both the proportion and proliferation of regulatory T cells increased and remained elevated with serial dose-intensified temozolomide cycles. Median progression-free and overall survival were 25.3 months and 41.1 months, respectively, exceeding survival using recursive partitioning analysis and matched historical controls.
“Overall, our results strengthen prior findings from other trials targeting cytomegalovirus and provide evidence for the association between pp65 targeting in glioblastoma and long-term survival,” concluded the study authors.
This study was funded by the National Institutes of Health.