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

被引：78

作者：

Narita, Yoshitaka ^{[1
]}

Arakawa, Yoshiki ^{[2
]}

Yamasaki, Fumiyuki ^{[3
]}

Nishikawa, Ryo ^{[4
]}

Aoki, Tomokazu ^{[5
]}

Kanamori, Masayuki ^{[6
]}

Nagane, Motoo ^{[7
]}

Kumabe, Toshihiro ^{[8
]}

Hirose, Yuichi ^{[9
]}

Ichikawa, Tomotsugu ^{[10
]}

Kobayashi, Hiroyuki ^{[11
]}

Fujimaki, Takamitsu ^{[12
]}

Goto, Hisaharu ^{[13
]}

Takeshima, Hideo ^{[14
]}

Ueba, Tetsuya ^{[15
]}

Abe, Hiroshi ^{[16
]}

Tamiya, Takashi ^{[17
]}

Sonoda, Yukihiko ^{[18
]}

Natsume, Atsushi ^{[19
]}

Kakuma, Tatsuyuki ^{[20
]}

Sugita, Yasuo ^{[21
]}

Komatsu, Nobukazu ^{[21
]}

Yamada, Akira ^{[21
]}

Sasada, Tetsuro ^{[22
]}

Matsueda, Satoko ^{[23
]}

Shichijo, Shigeki ^{[24
]}

Itoh, Kyogo ^{[24
]}

Terasaki, Mizuhiko ^{[25
]}

机构：

[1] Natl Canc Ctr, Tokyo, Japan

[2] Kyoto Univ, Grad Sch Med, Kyoto, Japan

[3] Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Hiroshima, Japan

[4] Saitama Med Univ, Int Med Ctr, Saitama, Japan

[5] Natl Hosp Org, Kyoto Med Ctr, Kyoto, Japan

[6] Tohoku Univ, Grad Sch Med, Sendai, Miyagi, Japan

[7] Kyorin Univ, Fac Med, Tokyo, Japan

[8] Kitasato Univ, Sch Med, Sagamihara, Kanagawa, Japan

[9] Fujita Hlth Univ, Sch Med, Toyoake, Aichi, Japan

[10] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Okayama, Japan

[11] Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido, Japan

[12] Saitama Med Univ Hosp, Saitama, Japan

[13] Yamaguchi Univ, Sch Med, Yamaguchi, Japan

[14] Univ Miyazaki, Fac Med, Miyazaki, Japan

[15] Kochi Med Sch, Kochi, Japan

[16] Fukuoka Univ, Fac Med, Fukuoka, Fukuoka, Japan

[17] Kagawa Univ, Fac Med, Takamatsu, Kagawa, Japan

[18] Yamagata Univ, Fac Med, Yamagata, Japan

[19] Nagoya Univ, Grad Sch Med, Nagoya, Aichi, Japan

[20] Kurume Univ, Biostat Ctr, Kurume, Fukuoka, Japan

[21] Kurume Univ, Sch Med, Fukuoka, Fukuoka, Japan

[22] Kanagawa Canc Ctr Res Inst, Canc Vaccine Ctr, Yokohama, Kanagawa, Japan

[23] Roswell Pk Canc Inst, Ctr Immunotherapy, Buffalo, NY 14263 USA

[24] Kurume Univ, Canc Vaccine Ctr, Kurume, Fukuoka, Japan

[25] Kurume Univ, Sch Med, Kurume, Fukuoka, Japan

来源：

NEURO-ONCOLOGY | 2019年 / 21卷 / 03期

关键词：

biomarker for overall survival; personalized peptide vaccine; phase III trial; pre-existing immunity; recurrent glioblastoma; IMMUNOLOGICAL EVALUATION; GROWTH-FACTOR; CELLS; BEVACIZUMAB; BIOMARKERS;

D O I：

10.1093/neuonc/noy200

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We conducted a phase III trial of personalized peptide vaccination (PPV) for human leukocyte antigen (HLA)-A24+ recurrent glioblastoma to develop a new treatment modality. 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 immunoglobulin G levels or the corresponding placebos were injected 1/week for 12 weeks. Our trial met neither the primary (overall survival [OS]) nor secondary endpoints. Unfavorable factors for OS of 58 PPV patients compared with 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 SART2-93 selection plus one of these 3 favorable factors (< 70 y old, 70 kg, or PS02) was significantly longer than that for the corresponding placebo patients (HR: 0.49, 0.44, and 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) compared with 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 chemokine C-C ligand 2 (CCL2), vascular endothelial growth factor, interleukin (IL)-6, IL-17, or haptoglobin, respectively. This phase III trial met neither the primary nor secondary endpoints.

引用

页码：348 / 359

页数：12

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