Skip to main content

Recurrent Glioblastoma Treated with Recombinant Poliovirus.

Publication ,  Journal Article
Desjardins, A; Gromeier, M; Herndon, JE; Beaubier, N; Bolognesi, DP; Friedman, AH; Friedman, HS; McSherry, F; Muscat, AM; Nair, S; Peters, KB ...
Published in: N Engl J Med
July 12, 2018

BACKGROUND: The prognosis of patients with recurrent World Health Organization (WHO) grade IV malignant glioma is dismal, and there is currently no effective therapy. We conducted a dose-finding and toxicity study in this population of patients, evaluating convection-enhanced, intratumoral delivery of the recombinant nonpathogenic polio-rhinovirus chimera (PVSRIPO). PVSRIPO recognizes the poliovirus receptor CD155, which is widely expressed in neoplastic cells of solid tumors and in major components of the tumor microenvironment. METHODS: We enrolled consecutive adult patients who had recurrent supratentorial WHO grade IV malignant glioma, confirmed on histopathological testing, with measurable disease (contrast-enhancing tumor of ≥1 cm and ≤5.5 cm in the greatest dimension). The study evaluated seven doses, ranging between 107 and 1010 50% tissue-culture infectious doses (TCID50), first in a dose-escalation phase and then in a dose-expansion phase. RESULTS: From May 2012 through May 2017, a total of 61 patients were enrolled and received a dose of PVSRIPO. Dose level -1 (5.0×107 TCID50) was identified as the phase 2 dose. One dose-limiting toxic effect was observed; a patient in whom dose level 5 (1010 TCID50) was administered had a grade 4 intracranial hemorrhage immediately after the catheter was removed. To mitigate locoregional inflammation of the infused tumor with prolonged glucocorticoid use, dose level 5 was deescalated to reach the phase 2 dose. In the dose-expansion phase, 19% of the patients had a PVSRIPO-related adverse event of grade 3 or higher. Overall survival among the patients who received PVSRIPO reached a plateau of 21% (95% confidence interval, 11 to 33) at 24 months that was sustained at 36 months. CONCLUSIONS: Intratumoral infusion of PVSRIPO in patients with recurrent WHO grade IV malignant glioma confirmed the absence of neurovirulent potential. The survival rate among patients who received PVSRIPO immunotherapy was higher at 24 and 36 months than the rate among historical controls. (Funded by the Brain Tumor Research Charity and others; ClinicalTrials.gov number, NCT01491893 .).

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

July 12, 2018

Volume

379

Issue

2

Start / End Page

150 / 161

Location

United States

Related Subject Headings

  • Young Adult
  • Survival Rate
  • Rhinovirus
  • Poliovirus
  • Oncolytic Virotherapy
  • Neoplasm Recurrence, Local
  • Middle Aged
  • Male
  • Infusions, Intralesional
  • Immunotherapy
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Desjardins, A., Gromeier, M., Herndon, J. E., Beaubier, N., Bolognesi, D. P., Friedman, A. H., … Bigner, D. D. (2018). Recurrent Glioblastoma Treated with Recombinant Poliovirus. N Engl J Med, 379(2), 150–161. https://doi.org/10.1056/NEJMoa1716435
Desjardins, Annick, Matthias Gromeier, James E. Herndon, Nike Beaubier, Dani P. Bolognesi, Allan H. Friedman, Henry S. Friedman, et al. “Recurrent Glioblastoma Treated with Recombinant Poliovirus.N Engl J Med 379, no. 2 (July 12, 2018): 150–61. https://doi.org/10.1056/NEJMoa1716435.
Desjardins A, Gromeier M, Herndon JE, Beaubier N, Bolognesi DP, Friedman AH, et al. Recurrent Glioblastoma Treated with Recombinant Poliovirus. N Engl J Med. 2018 Jul 12;379(2):150–61.
Desjardins, Annick, et al. “Recurrent Glioblastoma Treated with Recombinant Poliovirus.N Engl J Med, vol. 379, no. 2, July 2018, pp. 150–61. Pubmed, doi:10.1056/NEJMoa1716435.
Desjardins A, Gromeier M, Herndon JE, Beaubier N, Bolognesi DP, Friedman AH, Friedman HS, McSherry F, Muscat AM, Nair S, Peters KB, Randazzo D, Sampson JH, Vlahovic G, Harrison WT, McLendon RE, Ashley D, Bigner DD. Recurrent Glioblastoma Treated with Recombinant Poliovirus. N Engl J Med. 2018 Jul 12;379(2):150–161.

Published In

N Engl J Med

DOI

EISSN

1533-4406

Publication Date

July 12, 2018

Volume

379

Issue

2

Start / End Page

150 / 161

Location

United States

Related Subject Headings

  • Young Adult
  • Survival Rate
  • Rhinovirus
  • Poliovirus
  • Oncolytic Virotherapy
  • Neoplasm Recurrence, Local
  • Middle Aged
  • Male
  • Infusions, Intralesional
  • Immunotherapy