Cytokine gene polymorphisms are associated with response to blinatumomab in B-cell acute lymphoblastic leukemia.
acute lymphoblastic leukemia
blinatumomab
cytokine gene polymorphism
Journal
European journal of haematology
ISSN: 1600-0609
Titre abrégé: Eur J Haematol
Pays: England
ID NLM: 8703985
Informations de publication
Date de publication:
Jun 2021
Jun 2021
Historique:
revised:
02
03
2021
received:
16
12
2020
accepted:
03
03
2021
pubmed:
16
3
2021
medline:
30
11
2021
entrez:
15
3
2021
Statut:
ppublish
Résumé
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.
Substances chimiques
Antibodies, Bispecific
0
IL2 protein, human
0
Il17a protein, mouse
0
Interleukin-17
0
Interleukin-2
0
blinatumomab
4FR53SIF3A
Types de publication
Clinical Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
851-858Subventions
Organisme : NCI NIH HHS
ID : P30 CA033572
Pays : United States
Organisme : Next Generation of Research Scientists (HONORS) Award
Organisme : NIH HHS
ID : P30 CA033572
Pays : United States
Informations de copyright
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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