Department of Pharmacy Practice, Jefferson School of Pharmacy, Thomas Jefferson University, Philadelphia, PA, USA.
Ann Pharmacother. 2011 Oct;45(10):1248-55. doi: 10.1345/aph.1P780. Epub 2011 Sep 6.
To present the current clinical evidence on ofatumumab for use in refractory chronic lymphocytic leukemia (CLL).
A literature search was performed using MEDLINE and PubMed (both 1966-May 2011), as well as the American Society of Hematology abstracts (2000-May 2011), using the primary search terms ofatumumab and HuMax-CD20.
Clinical studies and abstracts available in the English language, describing the pharmacology, pharmacokinetics, clinical activity, and safety of ofatumumab in CLL were included in this review.
Ofatumumab is a human immunoglobulin monoclonal antibody that binds to B-lymphocytes expressing CD-20 cell surface antigens. Ofatumumab was granted accelerated approval by the Food and Drug Administration in October 2009 for the treatment of CLL refractory to fludarabine and alemtuzumab. A Phase 1/2 trial has established the safety and tolerability of single-agent ofatumumab at an initial dose of 300 mg intravenously on week 1, followed by 2000 mg once weekly for 7 doses (weeks 2-8), followed by 2000 mg once every 4 weeks for 4 doses (weeks 9-12), for a total of 12 doses. The final analysis of a pivotal international multicenter trial has shown promising activity in patients with CLL refractory to fludarabine and alemtuzumab, demonstrating overall response rates of 44-51%, with prolonged progression-free and overall survival. Ofatumumab activity has also been shown in a variety of other malignant and nonmalignant conditions, including non-Hodgkin lymphoma, rheumatoid arthritis, and multiple sclerosis. The most common adverse effect is grade 1 and 2 infusion reactions. Other adverse effects include infection, neutropenia, anemia, rash, fever, and diarrhea.
Clinical evidence suggests that ofatumumab is an effective agent in patients with CLL refractory to fludarabine and alemtuzumab. Data are awaited comparing ofatumumab to other salvage regimens. Until results of head-to-head trials are conducted comparing ofatumumab to existing regimens, it cannot be said whether ofatumumab is more efficacious or tolerable than currently available therapies.
介绍奥法木单抗在难治性慢性淋巴细胞白血病（CLL）中的临床应用现状。
应用 MEDLINE 和 PubMed（均回溯至 1966 年-2011 年 5 月）以及美国血液学会摘要（2000 年-2011 年 5 月）进行文献检索，检索的主要关键词包括奥法木单抗和 HuMax-CD20。
本综述纳入了在英语文献中描述奥法木单抗在 CLL 中的药理学、药代动力学、临床疗效和安全性的临床研究和摘要。
奥法木单抗是一种人源化免疫球蛋白单克隆抗体，与表达 CD-20 细胞表面抗原的 B 淋巴细胞结合。奥法木单抗于 2009 年 10 月获得美国食品和药物管理局加速批准，用于治疗氟达拉滨和阿仑单抗难治性 CLL。一项 1/2 期试验确定了单药奥法木单抗的安全性和耐受性，起始剂量为第 1 周静脉内给予 300mg，随后每周给予 2000mg，共 7 剂（第 2-8 周），然后每 4 周给予 2000mg，共 4 剂（第 9-12 周），共 12 剂。一项关键的国际多中心试验的最终分析显示，奥法木单抗在氟达拉滨和阿仑单抗难治性 CLL 患者中具有良好的疗效，总缓解率为 44%-51%，无进展生存期和总生存期延长。奥法木单抗在其他恶性和非恶性疾病中也具有疗效，包括非霍奇金淋巴瘤、类风湿关节炎和多发性硬化症。最常见的不良反应是 1 级和 2 级输注反应。其他不良反应包括感染、中性粒细胞减少、贫血、皮疹、发热和腹泻。
临床证据表明，奥法木单抗是氟达拉滨和阿仑单抗难治性 CLL 患者的有效治疗药物。目前正在比较奥法木单抗与其他挽救治疗方案的数据。在进行头对头试验比较奥法木单抗与现有方案之前，不能确定奥法木单抗是否比现有的治疗方法更有效或更耐受。
