Maloney D G, Grillo-López A J, White C A, Bodkin D, Schilder R J, Neidhart J A, Janakiraman N, Foon K A, Liles T M, Dallaire B K, Wey K, Royston I, Davis T, Levy R
Department of Medicine, Stanford University, CA, USA.
Blood. 1997 Sep 15;90(6):2188-95.
IDEC-C2B8 is a chimeric monoclonal antibody (MoAb) directed against the B-cell-specific antigen CD20 expressed on non-Hodgkin's lymphomas (NHL). The MoAb mediates complement and antibody-dependent cell-mediated cytotoxicity and has direct antiproliferative effects against malignant B-cell lines in vitro. Phase I trials of single doses up to 500 mg/m2 and 4 weekly doses of 375 mg/m2 showed clinical responses with no dose-limiting toxicity. We conducted a phase II, multicenter study evaluating four weekly infusions of 375 mg/m2 IDEC-C2B8 in patients with relapsed low-grade or follicular NHL (Working Formulation groups A-D). Patients were monitored for adverse events, antibody pharmacokinetics, and clinical response. Thirty-seven patients with a median age of 58 years (range, 29 to 81 years) were treated. All patients had relapsed after chemotherapy (median of 2 prior regimens) and 54% had failed aggressive chemotherapy. Infusional side effects (grade 1-2) consisting of mild fever, chills, respiratory symptoms, and occasionally hypotension were observed mostly with the initial antibody infusion and were rare with subsequent doses. Peripheral blood B-cell depletion occurred rapidly, with recovery beginning 6 months posttreatment. There were no significant changes in mean IgG levels and infections were not increased over what would be expected in this population. Clinical remissions were observed in 17 patients (3 complete remissions and 14 partial remissions), yielding an intent to treat response rate of 46%. The onset of these tumor responses was as soon as 1 month posttreatment and reached a maximum by 4 months posttreatment. In the 17 responders, the median time to progression was 10.2 months (5 patients exceeding 20 months). Likelihood of tumor response was associated with a follicular histology, with the ability to sustain a high serum level of antibody after the first infusion, and with a longer duration of remission to prior chemotherapy. One patient developed a detectable but not quantifiable immune response to the antibody that had no clinical significance. IDEC-C2B8 in a dose of 375 mg/m2 weekly for 4 weeks has antitumor activity in patients with relapsed low-grade or follicular NHL. Results with this brief, outpatient treatment compare favorably with results with standard chemotherapy, and IDEC-C2B8 has a better safety profile. Further studies evaluating IDEC-C2B8 in other types of lymphoma either alone or combined with chemotherapy are warranted.
IDEC-C2B8是一种嵌合单克隆抗体（MoAb），靶向非霍奇金淋巴瘤（NHL）上表达的B细胞特异性抗原CD20。该单克隆抗体介导补体和抗体依赖性细胞介导的细胞毒性，并在体外对恶性B细胞系具有直接的抗增殖作用。单剂量高达500mg/m²和4周剂量375mg/m²的I期试验显示出临床反应，且无剂量限制性毒性。我们进行了一项II期多中心研究，评估对复发的低度或滤泡性NHL患者（工作分类A-D组）每周输注4次375mg/m²的IDEC-C2B8。对患者进行不良事件、抗体药代动力学和临床反应监测。37例患者接受治疗，中位年龄58岁（范围29至81岁）。所有患者化疗后复发（既往化疗方案中位数为2种），54%患者对积极化疗无效。输注副作用（1-2级）包括轻度发热、寒战、呼吸道症状，偶尔有低血压，大多在首次输注抗体时出现，后续剂量时少见。外周血B细胞迅速耗竭，治疗后6个月开始恢复。平均IgG水平无显著变化，感染发生率未高于该人群预期。17例患者出现临床缓解（3例完全缓解，14例部分缓解），意向性治疗缓解率为46%。这些肿瘤反应最早在治疗后1个月出现，治疗后4个月达到高峰。在17例缓解者中，中位进展时间为10.2个月（5例超过20个月）。肿瘤反应的可能性与滤泡组织学、首次输注后维持高血清抗体水平的能力以及既往化疗缓解持续时间较长有关。1例患者对该抗体产生了可检测但不可量化的免疫反应，无临床意义。每周1次、共4周给予375mg/m²的IDEC-C2B8对复发的低度或滤泡性NHL患者具有抗肿瘤活性。这种简短的门诊治疗结果与标准化疗结果相比具有优势，且IDEC-C2B8安全性更好。有必要进一步研究单独或联合化疗评估IDEC-C2B8在其他类型淋巴瘤中的作用。
