Combining high-dose temozolomide chemotherapy with vaccination against cytomegalovirus (CMV) antigen pp65 was associated with surprisingly long survival times among patients with glioblastoma (GBM), according to a small phase 1 cohort study published in Clinical Cancer Research.1

When treated with concurrent temozolomide chemoradiation, GBM carries median survival of 14.6 months.

Although the phase 1 trial was not designed to assess treatment efficacy, combined vaccine-chemotherapy was associated with a median progression-free survival (PFS) of 25.3 months and a median overall survival time of 41.1 months.

Four patients had not progressed for more than 4.9 years and 3 patients had not progressed more than 7 years post-diagnosis.

Noting that CMV viral proteins are expressed in 90% of GBM tumors, the researchers used an anti-pp65 dendritic cell vaccine to make GBM cells recognizable to patients’ immune cells.

Eleven study participants had newly diagnosed glioblastoma. They received dose-intense temozolomide with 3 or more vaccinations of pp65 dendritic cells mixed with adjuvant granulocyte macrophage colony-stimulating factor (GM-CSF).

After combined treatment, the proportion and proliferation of regulatory T cells (Tregs) climbed and remained elevated, the team reported. Adverse events included known temozolomide-related toxicities such as nausea, fatigue, thrombocytopenia, and pronounced lymphopenia. No treatment-limiting toxicities occurred.

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“No known prognostic factors (age, Karnofsky performance status [KPS], IDH-1/2 mutation, and MGMT promoter methylation) predicted more favorable outcomes for the patients in this cohort,” the study authors reported.

References

  1. Batich KA, Reap EA, Archer GE, et al. Long-term survival in glioblastoma with cytomegalovirus pp65-targeted vaccination. Clin Cancer Res. 2017 Apr 14. doi: 10.1158/1078-0432-CCR-16-2057 [Epub ahead of print]