Effects of CTLA-4 Single Nucleotide Polymorphisms on Toxicity of Ipilimumab-Containing Regimens in Patients With Advanced Stage Melanoma.
J Immunother
; 47(5): 190-194, 2024 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-38318726
ABSTRACT
Single nucleotide polymorphisms (SNPs) in the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) gene, an inhibitor of T-cell priming, are associated with auto and alloimmunity. Studies implied a role for these SNPs as surrogate markers for immunotherapy-outcome in patients with melanoma. However, no predictive SNPs are defined to date. We analyzed different CTLA-4 SNPs in a large multicenter cohort of patients with ipilimumab-treated melanoma and investigated possible correlations with treatment-related outcomes. Archival blood and/or tumor tissue samples were collected from 361 patients with advanced-stage ipilimumab-treated (±nivolumab) in 6 Swiss and Dutch hospitals. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry based DNA genotyping was performed for 10 different CTLA-4 SNPs 49A>G, CT60G>A, Jo27T>C, Jo30G>A, Jo31G>T, -658C>T, -1722T>C, -1661A>G, 318C>T, and C>T rs1863800. Associations between different allele genotypes and occurrence of grade ≥3 adverse events (AEs) and survival were tested using univariable logistic regressions or Cox proportional hazard models. 262/361 (73%) patients could be analyzed; 65% of those were males, the median age was 58 years, 39% showed a partial or complete response, and 65% had ≥1 AEs. A TT-genotype of -1722T>C SNP was significantly associated with a lower incidence of grade ≥3 AEs ( P = 0.049), whereas the GG-genotype of CT60G>A correlated with a higher incidence of grade ≥3 AEs ( P = 0.026). The TT-genotype of Jo27T>C SNP ( P = 0.056) and GG-genotype of Jo31G>T ( P = 0.046) were associated with overall survival. CTLA-4 SNPs might predict treatment-related outcomes in patients with melanoma receiving ipilimumab. Confirmatory studies are needed to fully exploit those findings as predictive biomarkers for ipilimumab AEs.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Polimorfismo de Nucleotídeo Único
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Antígeno CTLA-4
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Ipilimumab
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Melanoma
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Estadiamento de Neoplasias
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Immunother
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J. immunother
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Journal of immunotherapy
Assunto da revista:
ALERGIA E IMUNOLOGIA
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NEOPLASIAS
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TERAPEUTICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Holanda