Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, 93-510 Lodz, ul. Ciołkowskiego 2, Poland.
Expert Rev Anticancer Ther. 2010 Oct;10(10):1529-43. doi: 10.1586/era.10.132.
Over the last few years, several monoclonal antibodies have been investigated in patients with B-cell lymphoid malignancies. Rituximab is the most important monoclonal antibody of clinical value in these disorders. Rituximab is an IgG1 chimeric antibody containing murine light- and heavy-chain variable region sequences and human constant region sequences. Since approval in 1997, rituximab has become the standard of care in follicular B-cell lymphoma, chronic lymphocytic leukemia (CLL) and aggressive lymphoma when combined with chemotherapy. Higher clinical benefits of rituximab can be seen in patients with CLL when it is added to other chemotherapeutic agents. Several recent reports have suggested that in patients with CLL, rituximab combined with purine nucleoside analogs (PNAs) or PNAs and cyclophosphamide may improve the results with acceptable toxicity, both in previously untreated and refractory/relapsed patients. The randomized, multinational Phase III study (REACH trial) has shown that rituximab combined with fludarabine and cyclophosphamide (R-FC regimen) results in 10 months longer progression-free survival, and higher overall response and complete response rates than fludarabine and cyclophosphamide (FC regimen) in previously treated patients. The German CLL study group initiated a multicenter, multinational Phase III trial, CLL8, to evaluate the efficacy and tolerability of R-FC versus FC for the first-line treatment of patients with advanced CLL. The overall response rate was significantly higher in the R-FC arm (95%) compared with FC (88%). The complete response rate in the R-FC arm was 44% compared with 27% in the FC arm. The recently updated analysis has demonstrated longer overall survival in the R-FC group. Recent clinical observations have revealed that combinations of rituximab with pentostatin and cyclophosphamide, or cladribine and cyclophosphamide are also highly active regimens in previously untreated CLL. In addition, the results of treatment with high-dose methylprednisolone in combination with rituximab in advanced CLL resistant to fludarabine have been reported recently by several groups. However, available therapies are only partially effective in CLL, exposing an obvious need to develop new, more specific and active drugs. Recently, several new anti-CD20 monoclonal antibodies have been developed and are now being evaluated in clinical trials.
在过去的几年中，已经有几种单克隆抗体在 B 细胞淋巴瘤患者中进行了研究。利妥昔单抗是这些疾病中具有临床价值的最重要的单克隆抗体。利妥昔单抗是一种 IgG1 嵌合抗体，包含鼠轻链和重链可变区序列以及人恒定区序列。自 1997 年批准以来，利妥昔单抗已成为滤泡性 B 细胞淋巴瘤、慢性淋巴细胞白血病 (CLL) 和侵袭性淋巴瘤的治疗标准，与化疗联合使用时更是如此。当添加其他化疗药物时，CLL 患者可从利妥昔单抗中获得更高的临床益处。最近的几份报告表明，在 CLL 患者中，利妥昔单抗联合嘌呤核苷类似物 (PNA) 或 PNA 和环磷酰胺可能会改善结果，同时具有可接受的毒性，无论是在未经治疗的患者还是在难治性/复发性患者中。随机、多中心 III 期研究 (REACH 试验) 表明，与氟达拉滨和环磷酰胺 (FC 方案) 相比，利妥昔单抗联合氟达拉滨和环磷酰胺 (R-FC 方案) 可使无进展生存期延长 10 个月，并且在先前治疗过的患者中，总缓解率和完全缓解率更高。德国 CLL 研究小组启动了一项多中心、多国 III 期试验 CLL8，以评估 R-FC 与 FC 在初治晚期 CLL 患者中的疗效和耐受性。R-FC 组的总缓解率明显高于 FC 组（95%比 88%）。R-FC 组的完全缓解率为 44%，而 FC 组为 27%。最近更新的分析表明，R-FC 组的总生存期更长。最近的临床观察显示，利妥昔单抗联合喷司他丁和环磷酰胺或克拉屈滨和环磷酰胺在初治 CLL 中也是高度有效的方案。此外，最近几个小组报告了治疗对氟达拉滨耐药的晚期 CLL 时，高剂量甲基强的松龙联合利妥昔单抗的治疗结果。然而，目前的治疗方法在 CLL 中仅部分有效，这表明迫切需要开发新的、更特异和更有效的药物。最近，已经开发了几种新的抗 CD20 单克隆抗体，目前正在临床试验中进行评估。
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