Study Finds Vaccine-Chemotherapy Combination Prolongs Overall Survival in Glioblastoma

Key Points

  • A vaccine targeting cytomegalovirus antigen pp65, combined with high-dose temozolomide, improved both progression-free and overall survival for a small group of patients with glioblastoma.
  • The cohort of 11 patients in the study who received the combination therapy demonstrated a median progression-free survival of 25.3 months and a median overall survival of 41.1 months. Four patients remained progression-free at 59 to 64 months from diagnosis.

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.

Study Methodology

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 x 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.

Study Results

Following dose-intensified temozolomide cycle one and three 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.

Four patients remained progression-free at 59 to 64 months from diagnosis. No known prognostic factors, such as age, Karnofsky performance status, isocitrate dehydrogenase 1/2 mutation, and methylguanine methyltransferase promoter methylation, predicted more favorable outcomes for the patients in this cohort.

“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.

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.

This study was funded by the National Institutes of Health.

 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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