Department of Medicine, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, CA 94305, USA.
Haematologica. 2012 Jan;97(1):30-7. doi: 10.3324/haematol.2011.045997. Epub 2011 Oct 11.
This phase I trial was conducted to determine the safety and pharmacokinetics of monoclonal antibody 216, a human monoclonal Immunoglobulin M antibody targeting a linear B-cell lactosamine antigen, administered alone and in combination with vincristine in patients with relapsed or refractory B-cell acute lymphoblastic leukemia, and to preliminarily assess tumor targeting and efficacy.
Three cohorts of patients received escalating doses of monoclonal antibody 216 administered as an intravenous infusion. In the case of poor response to the first dose of monoclonal antibody 216 alone, defined as less than 75% reduction in peripheral blood blast count, a second dose of the antibody with vincristine was given between days 4 and 7. Responses were assessed weekly until day 35. Serum concentration of monoclonal antibody 216 was measured before and after infusion. Monoclonal antibody 216 targeting was determined with an anti-idiotypic antibody to monoclonal antibody 216 and preliminary efficacy was analyzed by changes in peripheral blood blasts.
Thirteen patients were enrolled. One episode of grade 3 epistaxis was the only dose-limiting toxicity observed. All patients showed a poor response to the first monoclonal antibody 216 infusion with a decrease in peripheral blasts from 6-65% in 9 patients. In 8 patients, addition of vincristine to monoclonal antibody 216 resulted in an average reduction of the peripheral blasts of 81%. One patient without peripheral blasts achieved a hypoplastic marrow without evidence of leukemia after one infusion of monoclonal antibody 216 and monoclonal antibody 216/vincristine each. Monoclonal antibody 216 was detected on peripheral blasts in all patients.
Treatment with monoclonal antibody 216 in combination with vincristine is feasible and well tolerated in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Binding of monoclonal antibody 216 to leukemic blasts was efficient, and favorable early responses were observed.
本研究旨在评估单克隆抗体 216 的安全性和药代动力学，该药是人源化单克隆免疫球蛋白 M 抗体，可靶向 B 细胞线性乳糖胺抗原，用于治疗复发或难治性 B 细胞急性淋巴细胞白血病患者，评估其单独应用和联合长春新碱的疗效。
3 组患者接受递增剂量的单克隆抗体 216 静脉输注。若单克隆抗体 216 单药治疗首剂量反应不佳（定义为外周血原始细胞计数减少小于 75%），则于第 4 至 7 天加用单克隆抗体 216 联合长春新碱。每周评估疗效至第 35 天。于输注前后检测单克隆抗体 216 血清浓度。采用抗单克隆抗体 216 免疫原性抗体检测单克隆抗体 216 靶向性，并分析外周血原始细胞减少的初步疗效。
共纳入 13 例患者。唯一的剂量限制毒性是 1 例 3 级鼻出血。9 例患者首次单克隆抗体 216 输注后外周血原始细胞下降 6%至 65%，反应均不佳。8 例患者加用长春新碱后，外周血原始细胞平均减少 81%。1 例患者在单药输注单克隆抗体 216 及单克隆抗体 216/长春新碱后骨髓增生低下，外周血原始细胞无白血病。所有患者外周血原始细胞均能检测到单克隆抗体 216。
在复发或难治性 B 细胞急性淋巴细胞白血病患者中，单克隆抗体 216 联合长春新碱治疗是可行的，且耐受良好。单克隆抗体 216 与白血病细胞结合有效，观察到早期疗效较好。
