Department of Hematology, Karolinska University Hospital Solna, Stockholm, Sweden.
Expert Opin Biol Ther. 2010 Mar;10(3):439-49. doi: 10.1517/14712590903586239.
Since relapse of chronic lymphocytic leukemia (CLL), and refractoriness to treatment following relapse, is inevitable after initial treatment, development of novel treatment strategies is necessary.
CD20 as a therapeutic target for CLL, successes and limitations of current anti-CD20 monoclonal antibody (mAb) therapy, and implications of preclinical and clinical developments of novel alternatives, including ofatumumab, that may enhance anti-CD20 mAb therapy are reviewed. The literature reviewed encompasses papers and congress abstracts from the past 13 years.
While rituximab combined with chemotherapy has considerably improved outcomes for some but not all CLL patients, single-agent use is limited in relapsed/refractory CLL. Novel anti-CD20 mAbs in development, such as ofatumumab, may bypass some limitations by virtue of alternative epitope binding and modified effector functions. Ofatumumab induces significant complement-dependent cell lysis in vitro, particularly in cells with low CD20 expression. The FDA recently approved ofatumumab for treatment of CLL refractory to fludarabine and alemtuzumab.
CD20-targetting chemoimmunotherapeutic options have advanced treatment of CLL. Results for single-agent ofatumumab and other new CD20 mAbs, in different lines of therapy and in combination with chemotherapy, will guide optimal use of these alternative therapies for B-cell malignancies.
由于慢性淋巴细胞白血病（CLL）的复发，以及在初始治疗后复发后的难治性，是不可避免的，因此需要开发新的治疗策略。
CD20 作为 CLL 的治疗靶点，目前抗 CD20 单克隆抗体（mAb）治疗的成功和局限性，以及新型替代物的临床前和临床发展的意义，包括奥法木单抗，这可能增强抗 CD20 mAb 治疗。综述中包含了过去 13 年的论文和会议摘要。
虽然利妥昔单抗联合化疗已经显著改善了一些但不是所有 CLL 患者的预后，但在复发/难治性 CLL 中，单一药物的使用是有限的。正在开发的新型抗 CD20 mAbs，如奥法木单抗，可能通过替代表位结合和修饰的效应功能来绕过一些局限性。奥法木单抗在体外诱导显著的补体依赖性细胞裂解，特别是在 CD20 表达较低的细胞中。美国食品和药物管理局最近批准奥法木单抗用于治疗对氟达拉滨和阿仑单抗耐药的 CLL。
针对 CD20 的化疗免疫治疗选择已经推进了 CLL 的治疗。单药奥法木单抗和其他新型 CD20 mAbs 的结果，在不同的治疗线和与化疗联合使用时，将指导这些替代疗法在 B 细胞恶性肿瘤中的最佳应用。
