Rituximab has been approved in combination with fludarabine and cyclophosphamide for a new hematologic cancer: CD20-positive chronic lymphocytic leukemia, whether or not it has previously treated.

The U.S. Food and Drug Administration announcement on Feb. 18 makes rituximab the third drug that the agency has approved for the treatment of chronic lymphocytic leukemia (CLL) since 2008. The other drugs are ofatumumab, which was approved in October 2009 for patients whose cancer stopped being controlled by other forms of chemotherapy, and bendamustine, approved in March 2008 for untreated patients.

The addition of rituximab underscores the “FDA’s commitment to expediting the development and approval of drugs for patients with serious and life-threatening diseases,” Dr. Richard Pazdur, director of the FDA’s Office of Oncology Drug Products, said in a statement to the press.

A therapeutic antibody administered intravenously, rituximab binds to CD20 (cluster of differentiation 20), a protein on the surface of cancer and normal B cells. It is marketed in the United States by Genentech Inc. (a part of the Roche Group) and Biogen Idec Inc.

Since rituximab was first approved in the United States in 1997 for relapsed or refractory low-grade or follicular CD20-positive B-cell non-Hodgkin’s lymphoma (NHL), it has also been approved for other types of NHL, and in 2006 it was approved for treating rheumatoid arthritis.

The FDA based the new indication on two phase III trials that found that median progression-free survival was extended when CLL patients were treated with rituximab.

In one study of 817 untreated patients, progression-free survival was 8 months longer among those who were treated with rituximab plus fludarabine and cyclophosphamide (FC) chemotherapy, compared with those who received FC chemotherapy alone. Patients in the rituximab-plus-FC arm went a median 39.8 months without a worsening of disease vs. 31.5 months in the FC-alone arm.

This trial was conducted by the German CLL Study Group and sponsored by Roche, according to a statement on the Genentech Web site.

In the second study, the REACH (Rituximab Plus Chemotherapy in Relapsed/Refractory Chronic Lymphocytic Leukemia) trial, the population comprised 522 patients with CLL that had progressed after treatment with other chemotherapy treatments. Median progression-free survival was 5 months longer among those who were treated with rituximab and FC chemotherapy, again compared with those who received chemotherapy alone. The time until the condition worsened in these patients was 26.7 months and 21.7 months, respectively.

Genentech described REACH as a global, multicenter, randomized, open-label, phase III study sponsored by Genentech, Biogen Idec, and Roche.

In addition, the FDA noted that it had focused an analysis on patients aged 70 years and older who had been treated with rituximab. The analysis found no evidence that adding rituximab to chemotherapy was beneficial in this population, but there was no evidence that it was harmful, the agency said.

No new safety signals were seen in either study, according to the Genentech statement. The serious adverse events associated with rituximab included cytopenias. Infusion reactions, tumor lysis syndrome, and severe (and sometimes fatal) mucocutaneous reactions are listed in a boxed warning in the label.

The treatment regimen for CLL is 375 mg/m² on the day prior to FC chemotherapy in the first 28-day cycle, and then 500 mg/m² on day 1 of cycles 2-6, according to the label.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

利妥昔单抗已获准与氟达拉滨和环磷酰胺联合用于治疗一种新的血液恶性肿瘤：之前曾接受治疗或未接受过治疗的CD20阳性慢性淋巴细胞白血病(CLL)患者。

 

美国食品药品管理局(FDA)于2月18日发布的这项声明使利妥昔单抗成为该机构自2008年以来批准用于治疗CLL的第3种药物。另外两种药物分别为ofatumumab和苯达莫司汀，前者于2009年10月通过审批，适应证为其他类型化疗药物无法控制的CLL患者，后者于2008年3月通过审批，适应证为未经治疗的CLL患者。

 

增加利妥昔单抗适应证的举措突显了“FDA为严重和危及生命疾病患者治疗药物的研发和批准开辟快捷通道的承诺”。FDA肿瘤药品办公室主任Richard Pazdu博士在新闻发布会上的声明中指出。

 

利妥昔单抗是一种通过静脉内途径给药的治疗性抗体，可与体内肿瘤和正常B细胞表面蛋白CD20(分化抗原决定簇20)结合。这种药物在美国的经销商为基因泰克公司(罗氏公司的子公司)和生物基因艾迪克公司。

 

1997年，利妥昔单抗首先在美国获准用于治疗复发及难治性低分级或滤泡型CD20阳性B细胞性非霍奇金淋巴瘤(NHL)，其后又获准用于治疗其他类型的NHL，并于2006年获准用于治疗类风湿关节炎。

 

FDA对该药物新适应证的批准是基于两项III期临床试验的结果，这两项研究显示，CLL患者接受利妥昔单抗治疗后中位无进展生存期延长。

 

在其中一项包括817例未经治疗患者的研究中，利妥昔单抗+氟达拉滨和环磷酰胺(FC)化疗患者较单纯接受FC化疗患者无进展生存期延长了8个月。利妥昔单抗+FC化疗组患者中位至疾病进展时间为39.8个月，而单纯FC化疗组为31.5个月。

 

根据基因泰克公司网站的一项声明，该试验由德国CLL研究组进行，由罗氏公司资助。

 

在第2项研究——REACH(利妥昔单抗+化疗治疗复发/难治性慢性淋巴细胞白血病)试验中，纳入522例经其他化疗方案治疗后疾病进展的CLL患者。该试验结果再次显示，与单纯接受化疗的患者相比，利妥昔单抗+FC化疗患者的中位无进展生存期延长了5个月，两组患者的至疾病进展时间分别为21.7和26.7个月。

 

基因泰克公司将REACH研究描述为一项由基因泰克、生物基因艾迪克和罗氏公司共同发起的全球性、多中心、随机、开放性III期研究。

 

另外，FDA指出，该机构着重对接受利妥昔单抗治疗的70岁及以上患者进行了分析。这项分析发现，无证据显示，对于这一人群，在化疗基础上加用利妥昔单抗可获益，但也无证据显示，这种治疗方式有害，FDA发言人说。

 

根据基因泰克公司的声明，两项研究中均未发现新的安全性信号。与利妥昔单抗相关的严重不良事件包括血小板减少。注射反应、肿瘤溶解综合征以及严重(有时为致死性)粘膜皮肤反应已列于标签的黑框警告中。

 

根据标签，利妥昔单抗用于CLL的治疗方案为：在第一个为期28天的周期中，于FC化疗前一天给予利妥昔单抗 375 mg/m² ，以后在第2~6个周期的第1天分别给予利妥昔单抗 500 mg/m²。

 

爱思唯尔  版权所有