Cytokine gene polymorphisms are associated with response to blinatumomab in B‐cell acute lymphoblastic leukemia
| العنوان: | Cytokine gene polymorphisms are associated with response to blinatumomab in B‐cell acute lymphoblastic leukemia |
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| المؤلفون: | Stephen J. Forman, Margaret R. O'Donnell, Vinod Pullarkat, Xiwei Wu, Anthony S. Stein, Joycelynne Palmer, Sally Mokhtari, Ibrahim Aldoss, Guido Marcucci, Samer K. Khaled, Dongyun Yang, Joo Y. Song, Ketevan Gendzekhadze, Ryotaro Nakamura, Wei Chen, Nikeshan Jeyakumar |
| المصدر: | European Journal of Haematology. 106:851-858 |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, Oncology, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Internal medicine, Antibodies, Bispecific, medicine, Humans, SNP, Child, Adverse effect, Aged, Retrospective Studies, business.industry, Interleukin-17, Hematology, General Medicine, Immunotherapy, Odds ratio, Middle Aged, medicine.disease, Cytokine release syndrome, 030220 oncology & carcinogenesis, Interleukin-2, Female, Blinatumomab, IL17A, Cytokine Release Syndrome, business, 030215 immunology, medicine.drug |
| الوصف: | 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. |
| تدمد: | 1600-0609 0902-4441 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3c61d3f540f5cbb016ddaaa10b028512Test https://doi.org/10.1111/ejh.13622Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....3c61d3f540f5cbb016ddaaa10b028512 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16000609 09024441 |
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