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Long-term Survival in Glioblastoma with Cytomegalovirus pp65-Targeted Vaccination.


ABSTRACT: Purpose: Patients with glioblastoma have less than 15-month median survival despite surgical resection, high-dose radiation, and chemotherapy with temozolomide. We previously demonstrated that targeting cytomegalovirus pp65 using dendritic cells (DC) can extend survival and, in a separate study, that dose-intensified temozolomide (DI-TMZ) and adjuvant granulocyte macrophage colony-stimulating factor (GM-CSF) potentiate tumor-specific immune responses in patients with glioblastoma. Here, we evaluated pp65-specific cellular responses following DI-TMZ with pp65-DCs and determined the effects on long-term progression-free survival (PFS) and overall survival (OS).Experimental Design: Following standard-of-care, 11 patients with newly diagnosed glioblastoma received DI-TMZ (100 mg/m2/d × 21 days per cycle) with at least three vaccines of pp65 lysosome-associated membrane glycoprotein mRNA-pulsed DCs admixed with GM-CSF on day 23 ± 1 of each cycle. Thereafter, monthly DI-TMZ cycles and pp65-DCs were continued if patients had not progressed.Results: Following DI-TMZ cycle 1 and three doses of pp65-DCs, pp65 cellular responses significantly increased. After DI-TMZ, both the proportion and proliferation of regulatory T cells (Tregs) increased and remained elevated with serial DI-TMZ cycles. Median PFS and OS were 25.3 months [95% confidence interval (CI), 11.0-?] and 41.1 months (95% CI, 21.6-?), 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 [age, Karnofsky performance status (KPS), IDH-1/2 mutation, and MGMT promoter methylation] predicted more favorable outcomes for the patients in this cohort.Conclusions: Despite increased Treg proportions following DI-TMZ, patients receiving pp65-DCs showed long-term PFS and OS, confirming prior studies targeting cytomegalovirus in glioblastoma. Clin Cancer Res; 23(8); 1898-909. ©2017 AACR.

SUBMITTER: Batich KA 

PROVIDER: S-EPMC5559300 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Long-term Survival in Glioblastoma with Cytomegalovirus pp65-Targeted Vaccination.

Batich Kristen A KA   Reap Elizabeth A EA   Archer Gary E GE   Sanchez-Perez Luis L   Nair Smita K SK   Schmittling Robert J RJ   Norberg Pam P   Xie Weihua W   Herndon James E JE   Healy Patrick P   McLendon Roger E RE   Friedman Allan H AH   Friedman Henry S HS   Bigner Darell D   Vlahovic Gordana G   Mitchell Duane A DA   Sampson John H JH  

Clinical cancer research : an official journal of the American Association for Cancer Research 20170401 8


<b>Purpose:</b> Patients with glioblastoma have less than 15-month median survival despite surgical resection, high-dose radiation, and chemotherapy with temozolomide. We previously demonstrated that targeting cytomegalovirus pp65 using dendritic cells (DC) can extend survival and, in a separate study, that dose-intensified temozolomide (DI-TMZ) and adjuvant granulocyte macrophage colony-stimulating factor (GM-CSF) potentiate tumor-specific immune responses in patients with glioblastoma. Here, w  ...[more]

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