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

Yoshitaka Narita, Yoshiki Arakawa, Fumiyuki Yamasaki, Ryo Nishikawa, Tomokazu Aoki, Masayuki Kanamori, Motoo Nagane, Toshihiro Kumabe, Yuichi Hirose, Tomotsugu Ichikawa, Hiroyuki Kobayashi, Takamitsu Fujimaki, Hisaharu Goto, Hideo Takeshima, Tetsuya Ueba, Hiroshi Abe, Takashi Tamiya, Yukihiko Sonoda, Atsushi Natsume, Tatsuyuki KakumaYasuo Sugita, Nobukazu Komatsu, Akira Yamada, Tetsuro Sasada, Satoko Matsueda, Shigeki Shichijo, Kyogo Itoh, Mizuhiko Terasaki

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background. 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. 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 immunoglobulin G levels or the corresponding placebos were injected 1×/week for 12 weeks. Results. 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 PS0-2) 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. Conclusion. This phase III trial met neither the primary nor secondary endpoints.

Original languageEnglish
Pages (from-to)348-359
Number of pages12
JournalNeuro-Oncology
Volume21
Issue number3
DOIs
Publication statusPublished - 01-01-2019

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Glioblastoma
Vaccination
Peptides
Placebos
Survival
HLA Antigens
CC Chemokines
Haptoglobins
T-Lymphocyte Epitopes
Interleukin-17
Cytotoxic T-Lymphocytes
Immunosuppressive Agents
Vascular Endothelial Growth Factor A
Monocytes
Immunity
Interleukin-6
Immunoglobulin G
Biomarkers
Body Weight
Ligands

All Science Journal Classification (ASJC) codes

  • Oncology
  • Clinical Neurology
  • Cancer Research

Cite this

Narita, Y., Arakawa, Y., Yamasaki, F., Nishikawa, R., Aoki, T., Kanamori, M., ... Terasaki, M. (2019). A randomized, double-blind, phase III trial of personalized peptide vaccination for recurrent glioblastoma. Neuro-Oncology, 21(3), 348-359. https://doi.org/10.1093/neuonc/noy200
Narita, Yoshitaka ; Arakawa, Yoshiki ; Yamasaki, Fumiyuki ; Nishikawa, Ryo ; Aoki, Tomokazu ; Kanamori, Masayuki ; Nagane, Motoo ; Kumabe, Toshihiro ; Hirose, Yuichi ; Ichikawa, Tomotsugu ; Kobayashi, Hiroyuki ; Fujimaki, Takamitsu ; Goto, Hisaharu ; Takeshima, Hideo ; Ueba, Tetsuya ; Abe, Hiroshi ; Tamiya, Takashi ; Sonoda, Yukihiko ; Natsume, Atsushi ; Kakuma, Tatsuyuki ; Sugita, Yasuo ; Komatsu, Nobukazu ; Yamada, Akira ; Sasada, Tetsuro ; Matsueda, Satoko ; Shichijo, Shigeki ; Itoh, Kyogo ; Terasaki, Mizuhiko. / A randomized, double-blind, phase III trial of personalized peptide vaccination for recurrent glioblastoma. In: Neuro-Oncology. 2019 ; Vol. 21, No. 3. pp. 348-359.
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abstract = "Background. 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. 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 immunoglobulin G levels or the corresponding placebos were injected 1×/week for 12 weeks. Results. 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 PS0-2) 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. Conclusion. This phase III trial met neither the primary nor secondary endpoints.",
author = "Yoshitaka Narita and Yoshiki Arakawa and Fumiyuki Yamasaki and Ryo Nishikawa and Tomokazu Aoki and Masayuki Kanamori and Motoo Nagane and Toshihiro Kumabe and Yuichi Hirose and Tomotsugu Ichikawa and Hiroyuki Kobayashi and Takamitsu Fujimaki and Hisaharu Goto and Hideo Takeshima and Tetsuya Ueba and Hiroshi Abe and Takashi Tamiya and Yukihiko Sonoda and Atsushi Natsume and Tatsuyuki Kakuma and Yasuo Sugita and Nobukazu Komatsu and Akira Yamada and Tetsuro Sasada and Satoko Matsueda and Shigeki Shichijo and Kyogo Itoh and Mizuhiko Terasaki",
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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 2019, 'A randomized, double-blind, phase III trial of personalized peptide vaccination for recurrent glioblastoma', Neuro-Oncology, vol. 21, no. 3, pp. 348-359. https://doi.org/10.1093/neuonc/noy200

A randomized, double-blind, phase III trial of personalized peptide vaccination for recurrent glioblastoma. / Narita, Yoshitaka; Arakawa, Yoshiki; Yamasaki, Fumiyuki; Nishikawa, Ryo; Aoki, Tomokazu; Kanamori, Masayuki; Nagane, Motoo; Kumabe, Toshihiro; Hirose, Yuichi; Ichikawa, Tomotsugu; Kobayashi, Hiroyuki; Fujimaki, Takamitsu; Goto, Hisaharu; Takeshima, Hideo; Ueba, Tetsuya; Abe, Hiroshi; Tamiya, Takashi; Sonoda, Yukihiko; Natsume, Atsushi; Kakuma, Tatsuyuki; Sugita, Yasuo; Komatsu, Nobukazu; Yamada, Akira; Sasada, Tetsuro; Matsueda, Satoko; Shichijo, Shigeki; Itoh, Kyogo; Terasaki, Mizuhiko.

In: Neuro-Oncology, Vol. 21, No. 3, 01.01.2019, p. 348-359.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A randomized, double-blind, phase III trial of personalized peptide vaccination for recurrent glioblastoma

AU - Narita, Yoshitaka

AU - Arakawa, Yoshiki

AU - Yamasaki, Fumiyuki

AU - Nishikawa, Ryo

AU - Aoki, Tomokazu

AU - Kanamori, Masayuki

AU - Nagane, Motoo

AU - Kumabe, Toshihiro

AU - Hirose, Yuichi

AU - Ichikawa, Tomotsugu

AU - Kobayashi, Hiroyuki

AU - Fujimaki, Takamitsu

AU - Goto, Hisaharu

AU - Takeshima, Hideo

AU - Ueba, Tetsuya

AU - Abe, Hiroshi

AU - Tamiya, Takashi

AU - Sonoda, Yukihiko

AU - Natsume, Atsushi

AU - Kakuma, Tatsuyuki

AU - Sugita, Yasuo

AU - Komatsu, Nobukazu

AU - Yamada, Akira

AU - Sasada, Tetsuro

AU - Matsueda, Satoko

AU - Shichijo, Shigeki

AU - Itoh, Kyogo

AU - Terasaki, Mizuhiko

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background. 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. 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 immunoglobulin G levels or the corresponding placebos were injected 1×/week for 12 weeks. Results. 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 PS0-2) 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. Conclusion. This phase III trial met neither the primary nor secondary endpoints.

AB - Background. 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. 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 immunoglobulin G levels or the corresponding placebos were injected 1×/week for 12 weeks. Results. 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 PS0-2) 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. Conclusion. This phase III trial met neither the primary nor secondary endpoints.

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