Cytokine gene polymorphisms are associated with response to blinatumomab in B-cell acute lymphoblastic leukemia.
Eur J Haematol
; 106(6): 851-858, 2021 Jun.
Article
em En
| MEDLINE
| ID: mdl-33721333
ABSTRACT
Blinatumomab is a bispecific T cell-engaging antibody approved for treatment of relapsed/refractory (r/r) ALL, with 40%-50% complete response (CR)/CR with incomplete count recovery (CRi). Cytokine release syndrome (CRS) as a major adverse effect after blinatumomab therapy. Here, we evaluated the possible association between single-nucleotide polymorphisms (SNPs) in cytokine genes, disease response, and CRS in r/r ALL patients who received blinatumomab between 2012 and 2017 at our center (n = 66), using patients' archived DNA samples. With a median duration of 9.5 months (range 1-37), 37 patients (56.1%) achieved CR/CRi, 54 (81.8%) experienced CRS (G1 n = 35, G2 n = 14, G3 n = 5), and 9 (13.6%) developed neurotoxicity. By multivariable analysis, after adjusting for high disease burden, one SNP on IL2 (rs2069762), odds ratio (OR) = 0.074 (95% CI NE-0.43, P = .01) and one SNP on IL17A (rs4711998), OR = 0.28 (95% CI 0.078-0.92, P = .034) were independently associated with CR/CRi. None of the analyzed SNPs were associated with CRS. To our knowledge, this is the first study demonstrating a possible association between treatment response to blinatumomab and SNPs. Our hypothesis-generated data suggest a potential role for IL-17 and IL-2 in blinatumomab response and justify a larger confirmatory study, which may lead to personalized blinatumomab immunotherapy for B-ALL.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Leucemia-Linfoma Linfoblástico de Células Precursoras B
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Interleucina-2
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Anticorpos Biespecíficos
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Interleucina-17
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Polimorfismo de Nucleotídeo Único
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Síndrome da Liberação de Citocina
Tipo de estudo:
Observational_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article