TY - JOUR
T1 - Effect of HLA genotype on intravesical recurrence after bacillus Calmette–Guérin therapy for non-muscle-invasive bladder cancer
AU - Kobayashi, Mizuki
AU - Fujiyama, Nobuhiro
AU - Tanegashima, Tokiyoshi
AU - Narita, Shintaro
AU - Yamamoto, Yoshiaki
AU - Fujimoto, Naohiro
AU - Ueda, Shohei
AU - Takeuchi, Ario
AU - Numakura, Kazuyuki
AU - Habuchi, Tomonori
AU - Matsuyama, Hideyasu
AU - Eto, Masatoshi
AU - Shiota, Masaki
N1 - Funding Information:
This work was partly supported by grants (Nos. 21K06592, 19K18551) from the Japan Society for the Promotion of Science, Tokyo, Japan, and the Nakatomi Foundation, Tokyo, Japan.
Funding Information:
Shintaro Narita received honoraria from Janssen Pharmaceutical, Bayer Yakuhin, AstraZeneca, Takeda Pharmaceutical, Sanofi, and Astellas Pharma. Tomonori Habuchi received honoraria from Janssen Pharmaceutical, Takeda Pharmaceutical, Astellas Pharma, Daiichi Sankyo, AstraZeneca, Sanofi, and Bayer Yakuhin, and research funding support from Takeda Pharmaceutical, Astellas Pharma, Daiichi Sankyo, Sanofi, and Bayer Yakuhin. Masatoshi Eto received honoraria from Ono Pharmaceutical, Takeda Pharmaceutical, Novartis Pharma, Pfizer, Bristol-Myers Squibb, Janssen Pharmaceutical, MSD, and Merck Biopharma, and research funding support from Sanofi, Bayer Yakuhin, Astellas Pharma., Ono Pharmaceutical., and Takeda Pharmaceutical. Masaki Shiota received honoraria from Janssen Pharmaceutical, AstraZeneca, and Astellas Pharma, and research funding support from Daiichi Sankyo.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2022/3
Y1 - 2022/3
N2 - The intravesical administration of bacillus Calmette–Guérin (BCG) is widely used to control the intravesical recurrence of non-muscle-invasive bladder cancer (NMIBC). This study aimed to reveal the effects of zygosity on human leukocyte antigen (HLA) genes and individual HLA genotypes on intravesical recurrence after intravesical BCG therapy for NMIBC. This study included Japanese patients who had received intravesical BCG for NMIBC. HLA genotyping of HLA-A, B, C, and DRB1 was performed. The effect of HLA zygosity and HLA genotype on intravesical recurrence was evaluated. Among 195 patients, those homozygous for the HLA-B supertype were more likely than those heterozygous for the HLA-B supertype to experience intravesical recurrence by univariate analysis (hazard ratio [HR], 95% confidence interval [CI]; 1.87, 1.14–3.05, P = 0.012) and multivariate analysis (HR, 95% CI; 2.26, 1.02–5.01, P = 0.045). Patients with B07 or B44 had a decreased risk of intravesical recurrence by univariate analysis (HR, 95% CI; 0.43, 0.24–0.78, P = 0.0056) and multivariate analysis (HR, 95% CI; 0.36, 0.16–0.82, P = 0.016). This study suggests the importance of the diversity and specificity of HLA-B loci in the antitumor effect of BCG immunotherapy for NMIBC. These findings may contribute to the delineation of risk strata for BCG therapy and improve the medical management of NMIBC.
AB - The intravesical administration of bacillus Calmette–Guérin (BCG) is widely used to control the intravesical recurrence of non-muscle-invasive bladder cancer (NMIBC). This study aimed to reveal the effects of zygosity on human leukocyte antigen (HLA) genes and individual HLA genotypes on intravesical recurrence after intravesical BCG therapy for NMIBC. This study included Japanese patients who had received intravesical BCG for NMIBC. HLA genotyping of HLA-A, B, C, and DRB1 was performed. The effect of HLA zygosity and HLA genotype on intravesical recurrence was evaluated. Among 195 patients, those homozygous for the HLA-B supertype were more likely than those heterozygous for the HLA-B supertype to experience intravesical recurrence by univariate analysis (hazard ratio [HR], 95% confidence interval [CI]; 1.87, 1.14–3.05, P = 0.012) and multivariate analysis (HR, 95% CI; 2.26, 1.02–5.01, P = 0.045). Patients with B07 or B44 had a decreased risk of intravesical recurrence by univariate analysis (HR, 95% CI; 0.43, 0.24–0.78, P = 0.0056) and multivariate analysis (HR, 95% CI; 0.36, 0.16–0.82, P = 0.016). This study suggests the importance of the diversity and specificity of HLA-B loci in the antitumor effect of BCG immunotherapy for NMIBC. These findings may contribute to the delineation of risk strata for BCG therapy and improve the medical management of NMIBC.
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U2 - 10.1007/s00262-021-03032-0
DO - 10.1007/s00262-021-03032-0
M3 - Article
C2 - 34379177
AN - SCOPUS:85112246358
VL - 71
SP - 727
EP - 736
JO - Cancer Immunology and Immunotherapy
JF - Cancer Immunology and Immunotherapy
SN - 0340-7004
IS - 3
ER -