Cytokine gene polymorphisms are associated with response to blinatumomab in B‐cell acute lymphoblastic leukemia. (24th March 2021)

• Record Type: Journal Article
• Authors: 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; Nakamura, Ryotaro
• Is Part Of: European journal of haematology. Volume 106:Number 6(2021)
• Page Start: 851
• Page End: 858
• Publication Date: 2021-03-24
• Subjects: acute lymphoblastic leukemia -- blinatumomab -- cytokine gene polymorphism; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; Blood -- Periodicals; 616.15005
• DOI: 10.1111/ejh.13622
• Languages: English
• ISSNs: 0902-4441

Abstract

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.