Global Bioassays and Technology, Teva Pharmaceuticals, Inc., 145 Brandywine Parkway, West Chester, PA 19380, USA.
Merckle GmbH, Graf-Arco-Straße 3, 89079 Ulm, Germany.
J Immunol Res. 2016;2016:9248061. doi: 10.1155/2016/9248061. Epub 2016 Jun 23.
Lipegfilgrastim is a long-acting, once-per-cycle, glycopegylated recombinant granulocyte colony-stimulating factor (G-CSF) used to prevent neutropenia in patients receiving myelosuppressive chemotherapy. This integrated analysis examined the immunogenicity of lipegfilgrastim and its potential clinical impact in two double-blind randomized studies (phases II and III) of patients with breast cancer receiving chemotherapy. Serum samples were analyzed using sequential assays for screening, confirmation, antibody titer, and characterization of antidrug antibodies (ADA). Neutropenia-related efficacy measures were reviewed for each ADA-positive patient. Among 255 patients receiving lipegfilgrastim (154 in phase II, 101 in phase III) and 155 patients receiving pegfilgrastim (54 in phase II, 101 in phase III), the incidence of treatment-emergent ADA was low and similar between the lipegfilgrastim (phase II: 1.3%; phase III: 1.0%) and pegfilgrastim (phase II: 1.9%; phase III: 1.0%) arms. None of the treatment-emergent ADA-positive samples exhibited neutralizing activity against lipegfilgrastim, pegfilgrastim, or glycosylated G-CSF in a cell-based neutralizing antibody assay. No changes were observed in neutropenia-related efficacy measures among ADA-positive patients, and no treatment-related hypersensitivity or anaphylaxis occurred. These results indicate that there is no apparent impact of ADA on lipegfilgrastim efficacy and safety.
培格非格司亭是一种长效、每个周期只需使用一次的聚乙二醇化重组粒细胞集落刺激因子（G-CSF），用于预防接受骨髓抑制性化疗的患者中性粒细胞减少症。本综合分析检查了培格非格司亭的免疫原性及其在两项接受化疗的乳腺癌患者的双盲随机研究（II 期和 III 期）中的潜在临床影响。使用序贯检测法分析血清样本，以进行筛选、确证、抗体滴度和抗药物抗体（ADA）的表征。对每个 ADA 阳性患者的中性粒细胞减少相关疗效措施进行了回顾。在接受培格非格司亭（II 期 154 例，III 期 101 例）和培非格司亭（II 期 54 例，III 期 101 例）的 255 例患者中，治疗中出现 ADA 的发生率低，且培格非格司亭（II 期：1.3%；III 期：1.0%）和培非格司亭（II 期：1.9%；III 期：1.0%）之间无差异。治疗中出现的 ADA 阳性样本在基于细胞的中和抗体检测中均未显示对培格非格司亭、培非格司亭或糖基化 G-CSF 的中和活性。ADA 阳性患者的中性粒细胞减少相关疗效措施无变化，且未发生与治疗相关的过敏反应或过敏样反应。这些结果表明 ADA 对培格非格司亭的疗效和安全性无明显影响。
