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2018 ; 379
(2
): 150-161
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Recurrent Glioblastoma Treated with Recombinant Poliovirus
#MMPMID29943666
Desjardins A
; Gromeier M
; Herndon JE 2nd
; 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
N Engl J Med
2018[Jul]; 379
(2
): 150-161
PMID29943666
show ga
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 10(7) and 10(10) 50% tissue-culture
infectious doses (TCID(50)), 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 (5.0×10(7)
TCID(50)) was identified as the phase 2 dose. One dose-limiting toxic effect was
observed; a patient in whom dose level 5 (10(10) TCID(50)) 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 .).
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