A randomized, double-blind, phase III trial of personalized peptide vaccination for recurrent glioblastoma.

Related Articles

A randomized, double-blind, phase III trial of personalized peptide vaccination for recurrent glioblastoma.

Neuro Oncol. 2018 Nov 30;:

Authors: Narita Y, Arakawa Y, Yamasaki F, Nishikawa R, Aoki T, Kanamori M, Nagane M, Kumabe T, Hirose Y, Ichikawa T, Kobayashi H, Fujimaki T, Goto H, Takeshima H, Ueba T, Abe H, Tamiya T, Sonoda Y, Natsume A, Kakuma T, Sugita Y, Komatsu N, Yamada A, Sasada T, Matsueda S, Shichijo S, Itoh K, Terasaki M

Abstract
Background: We conducted a phase III trial of personalized peptide vaccination (PPV) for human leucocyte antigen (HLA)-A24+ recurrent glioblastoma to develop a new treatment modality.
Methods: We randomly assigned 88 recurrent glioblastoma patients to receive PPV (n=58) or the placebo (n=30) at a 2-to-1 ratio. Four of 12 warehouse peptides selected based on preexisting peptide-specific IgG levels or the corresponding placebos were injected 1/week for 12 weeks.
Results: Our trial met to neither the primary (overall survival, OS) nor secondary endpoints. Unfavorable factors for OS of 58 PPV patients as compared to 30 placebo patients were SART2-93 peptide selection (n=13 vs 8, hazard ratio<HR>;15.9), >=70 years old (4 vs 4, 7.87), >70 kg body weight (10 vs 7, 4.11), and performance status (PS)3 (8 vs 2, 2.82), respectively. Consequently, the median OS for PPV patients without SAR2-93 selection plus one of these 3 favorable factors (<70 years old, =<70kg, or PS0-2) was significantly longer than that for the corresponding placebo patients (HR; 0.49, 0.44, or 0.51), respectively. Preexisting immunity against both all 12 warehouse peptides besides SART2-93 and the other cytotoxic T lymphocyte epitope peptides was significantly depressed in the patients with SART2-93 selection (n=21) as compared to that of the patients without SART2-93 selection (n=67). Biomarkers correlative for favorable OS of the PPV patients were a lower percentage of CD11b+CD14+HLA-DRlow immunosuppressive monocytes and a higher percentage of CD4+CD45RA- activated T cells, the intermediate levels of CCL2, VEGF, IL-7, IL-17, or haptoglobin, respectively.
Conclusion: This phase III trial met to neither the primary nor secondary endpoints.

PMID: 30500939 [PubMed - as supplied by publisher]

from PubMed via alexandrossfakianakis on Inoreader https://ift.tt/2QfwnO7