Association of serum Rituximab (IDEC-C2B8) concentration and anti-tumor response in the treatment of recurrent low-grade or follicular non-Hodgkin's lymphoma
Association of serum Rituximab (IDEC-C2B8) concentration and anti-tumor response in the treatment of recurrent low-grade or follicular non-Hodgkin's lymphoma
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DOI：
10.1023/a:1008416911099
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发表时间：
1998-09-01
影响因子：
50.5
通讯作者：
Shen, D
中科院分区：
文献类型：
--
作者：
Berinstein, NL;Grillo-Lopez, AJ;Shen, D
背景：单克隆抗体被用于治疗低度恶性非霍奇金淋巴瘤以及其他癌症。从I期和II期临床研究的结果表明，嵌合单克隆抗体利妥昔单抗具有最小的毒性和显着的治疗活性，在低级别的非霍奇金淋巴瘤。患者和方法：我们最近报道了一个多中心的关键III期临床试验，涉及166例复发性低级别淋巴瘤谁与四输注利妥昔单抗治疗。80例患者（48%）达到客观缓解，包括10例患者（6%）达到完全缓解。总体而言，126例患者（76%）的总体肿瘤大小缩小≥ 20%。中位缓解持续时间和至进展时间分别为11.6和13.2个月。输注和长期毒性有限。在本报告中，我们描述了这些患者的药代动力学数据。所有患者在首次输注后均检测到可测量的利妥昔单抗浓度，并在整个治疗过程中增加。单克隆抗体的半衰期从第一次输注后的76.3小时增加至第四次输注后的205.8小时，同时抗体清除率降低4倍。在治疗后3个月和6个月，中位利妥昔单抗血清水平分别为20.3 μ g/ml（104例患者的范围为0.0 - 96.8 μ g/ml）和1.3 μ g/ml（13例患者的范围为0.0-28.7 μ g/ml）。在治疗和随访期间的多个时间点，发现中位抗体浓度和应答之间存在统计学显著相关性。平均血清抗体浓度也与肿瘤体积和基线循环B细胞数量呈负相关。我们得出结论，利妥昔单抗是治疗有效的B细胞淋巴瘤。药代动力学数据表明，某些患者亚组可能从增加剂量中获益，目前正在进行解决这一问题的研究。
Background, Monoclonal antibodies are being utilized for treatment of patients with low-grade non-Hodgkin's lymphoma as well as other cancers. Results from phase I and II clinical studies has shown that the chimeric monoclonal antibody Rituximab has minimal toxicity and significant therapeutic activity in low grade non-Hodgkin's lymphoma.Patients and methods: We have recently reported on a multicentre pivotal phase III clinical trial involving 166 patients with recurrent low-grade lymphoma who were treated with four infusions of Rituximab. Eighty patients (48%) achieved objective responses including 10 patients (6%) with complete responses. Overall, 126 patients (76%) had a greater than or equal to 20% reduction in overall tumor size. The median response duration and time to progression are 11.6 and 13.2 months, respectively. The infusional and long term toxicities were limited.Results. In this report we describe the pharmacokinetic data obtained on these patients. Measurable concentrations of Rituximab were detected in all patients after the first infusion and increased throughout the treatment course. The half-life of the monoclonal antibody increased from 76.3 hours after the first infusion to 205.8 hours after the fourth infusion and was concomitant with a four-fold decrease in the antibody clearance. At three months and six months post-treatment, the median Rituximab serum levels were 20.3 mu g/ml (range 0.0 to 96.8 mu g/ml in 104 patients) and 1.3 mu g/ml(range 0.0-28.7 mu g/ml in 13 patients), respectively. A statistically significant correlation was found between the median antibody concentration and response for multiple time points during the treatment and followup. The mean serum antibody concentration was also inversely correlated with measurements of tumor bulk and with the number of circulating B cells at baseline.Conclusions. We conclude that Rituximab is therapeutically effective against B-cell lymphoma. Pharmacokinetic data suggests that certain subsets of patients may possibly benefit from increased dosing and studies to address this are currently underway.