1. Cytokine gene polymorphisms are associated with response to blinatumomab in B‐cell acute lymphoblastic leukemia.
- Author
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Jeyakumar, Nikeshan, Aldoss, Ibrahim, Yang, Dongyun, Mokhtari, Sally, Gendzekhadze, Ketevan, Khaled, Samer, O'Donnell, Margaret, Palmer, Joycelynne, Song, Joo Y., Marcucci, Guido, Stein, Anthony S., Forman, Stephen J., Pullarkat, Vinod A., Chen, Wei, Wu, Xiwei, and Nakamura, Ryotaro
- Subjects
LYMPHOBLASTIC leukemia ,ACUTE leukemia ,GENETIC polymorphisms ,CYTOKINE release syndrome ,SINGLE nucleotide polymorphisms ,CD19 antigen - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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