Department of Hematology, Niguarda Ca' Granda Hospital, Milano, Italy.
Onco Targets Ther. 2010 Nov 26;3:227-46. doi: 10.2147/OTT.S8151.
The monoclonal chimeric anti-CD20 antibody, rituximab, has considerably improved therapeutic outcome in B-cell chronic lymphocytic leukemia. Rituximab has limited clinical activity when used as a single agent. The combination of the monoclonal antibody with fludarabine-based regimens clearly demonstrated, in Phase II and randomized trials, an increase in clinical efficacy in previously untreated and pretreated patients. Furthermore the addition of rituximab enabled the eradication of minimal residual disease, which is correlated with the prognosis in a high proportion of patients. Although the combination of rituximab with fludarabine-based regimens increased myelosuppression and immunosuppression, incidence of infections did not increase. The benefit of adding rituximab to other purine analogs or other chemotherapeutic combination regimens has also been explored. Moreover there could be a role for achieving better quality of responses with the combination of different monoclonal antibodies, considering that they target different antigens and exert different mechanism of action. Although the role of rituximab as maintenance therapy in low grade non-Hodgkin's lymphomas has been determined, the benefit and optimal schedule in chronic lymphocytic leukemia are still under investigation. This review brings together knowledge of the pharmacokinetics, mechanism of action and clinical use of rituximab in chronic lymphocytic leukemia.
单克隆嵌合抗 CD20 抗体利妥昔单抗显著改善了 B 细胞慢性淋巴细胞白血病的治疗效果。利妥昔单抗单药治疗的临床疗效有限。在 II 期和随机试验中，将该单克隆抗体与氟达拉滨为基础的方案联合应用，在未治疗和预处理的患者中均明显提高了临床疗效。此外，利妥昔单抗的加入使微小残留疾病得以清除，而微小残留疾病在很大一部分患者中与预后相关。虽然利妥昔单抗与氟达拉滨为基础的方案联合应用增加了骨髓抑制和免疫抑制，但感染的发生率并未增加。人们还探索了在其他嘌呤类似物或其他化疗联合方案中加入利妥昔单抗的益处。此外，考虑到不同的单克隆抗体针对不同的抗原并发挥不同的作用机制，联合使用可能会产生更好的反应质量。虽然已经确定了利妥昔单抗作为低度非霍奇金淋巴瘤维持治疗的作用，但在慢性淋巴细胞白血病中的益处和最佳方案仍在研究中。本文综述了利妥昔单抗在慢性淋巴细胞白血病中的药代动力学、作用机制和临床应用。
