Maloney D G, Grillo-López A J, Bodkin D J, White C A, Liles T M, Royston I, Varns C, Rosenberg J, Levy R
Department of Medicine, Stanford University, CA, USA.
J Clin Oncol. 1997 Oct;15(10):3266-74. doi: 10.1200/JCO.1997.15.10.3266.
To evaluate the safety, pharmacokinetics, and biologic effect of multiple doses of the chimeric anti-CD20 monoclonal antibody (mAb) IDEC-C2B8 in patients with relapsed B-cell lymphoma.
Twenty patients with relapsed low-grade (n = 15) or intermediate-/high-grade (n = 5) lymphoma received weekly infusions times four of 125 mg/m2 (n = 3), 250 mg/m2 (n = 7), or 375 mg/m2 (n = 10) of IDEC-C2B8.
Infusional side effects during the initial infusion were mainly grade I/II fever, asthenia, chills, nausea, rash, and urticaria. More serious events were rare. Peripheral-blood B cells were rapidly depleted and slowly recovered over 3 to 6 months. There was no change in mean immunoglobulin (Ig) levels. Antibody serum half-life (and maximum concentration [Cmax]) generally increased between the first and fourth infusions (33.2 hours v 76.6 hours, respectively) following the 375-mg/m2 doses. Six of 18 assessable patients had a partial remission (PR), with a median time to disease progression of 6.4 months (range, 3 to 21.7). Minor responses (MRs) were observed in five patients and progressive disease (PD) in seven. Tumor responses occurred in peripheral blood, bone marrow (BM), spleen, bulky lymph nodes, and extranodal sites, and in patients who had relapsed following high-dose myeloablative chemotherapy. Six of 14 patients (40%) with a low-grade histology responded. Four of six with bulky disease had a PR.
IDEC-C2B8 chimeric anti-CD20 mAb therapy is well tolerated and has clinical activity in patients with relapsed B-cell lymphoma. The 375-mg/m2 dose has been selected for a phase II trial in patients with relapsed low-grade or follicular B-cell lymphoma.
评估多次剂量的嵌合抗CD20单克隆抗体（mAb）IDEC-C2B8在复发B细胞淋巴瘤患者中的安全性、药代动力学和生物学效应。
20例复发的低度（n = 15）或中/高度（n = 5）淋巴瘤患者接受每周一次的输注，共4次，剂量分别为125 mg/m²（n = 3）、250 mg/m²（n = 7）或375 mg/m²（n = 10）的IDEC-C2B8。
首次输注期间的输注相关副作用主要为I/II级发热、乏力、寒战、恶心、皮疹和荨麻疹。更严重的事件罕见。外周血B细胞迅速耗竭，并在3至6个月内缓慢恢复。平均免疫球蛋白（Ig）水平无变化。375 mg/m²剂量组在第一次和第四次输注之间，抗体血清半衰期（和最大浓度 [Cmax]）通常增加（分别为33.2小时对76.6小时）。18例可评估患者中有6例部分缓解（PR），疾病进展的中位时间为6.4个月（范围3至21.7个月）。5例患者观察到微小反应（MR），7例患者疾病进展（PD）。肿瘤反应发生在外周血、骨髓（BM）、脾脏、肿大淋巴结和结外部位，以及接受大剂量清髓性化疗后复发的患者中。14例低度组织学患者中有6例（40%）有反应。6例有肿大病灶的患者中有4例部分缓解。
IDEC-C2B8嵌合抗CD20 mAb治疗耐受性良好，对复发B细胞淋巴瘤患者具有临床活性。已选择375 mg/m²剂量用于复发低度或滤泡性B细胞淋巴瘤患者的II期试验。
