Gazyva (obinutuzumab)
On November 1, 2013, the U.S. Food and Drug Administration approved obinutuzumab (GAZYVA™ injection, for intravenous use, Genentech, Inc.; previously known as GA101) for use in combination with chlorambucil for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL).
The approval was based on demonstration of an improvement in progression-free survival (PFS) in a randomized, open-label, multicenter trial comparing obinutuzumab in combination with chlorambucil (GClb) to chlorambucil (Clb) alone in patients with previously untreated CD20-positive CLL. The study also included a rituximab in combination with chlorambucil (RClb) arm. The results of RClb compared to GClb will be available at a later stage.
Patients randomized to the combination arm received 1000 mg doses of obinutuzumab intravenously on day 1 (later divided into 100 mg on day 1, followed by 900 mg on day 2), day 8 and day 15 of the first cycle. Chlorambucil, 0.5 mg/kg, was administered on days 1 and 15. During treatment cycles 2-6, patients received obinutuzumab, 1000 mg intravenously only on day 1 in combination with chlorambucil, 0.5 mg/kg, on days 1 and 15. Patients received pre-medication with a glucocorticoid, acetaminophen and anti-histamine prior to initial obinutuzumab infusions, and subsequently as needed. Patients assigned to single-agent chlorambucil received 0.5 mg/kg on days 1 and 15 of all treatment cycles (cycles 1 to 6). Cycles were repeated every 28 days.
A total of 356 patients were randomized (2:1) to GClb (n=238) and Clb (n=118). The median age was 73 years (range 39 -88). The independent review committee assessed median PFS was 23.0 and 11.1 months in the GClb and Clb arms, respectively [HR 0.16 (95% CI: 0.11, 0.24), log-rank p-value <0.0001].
The most common adverse reactions (greater than or equal to 10%) with obinutuzumab in combination with chlorambucil (with a higher frequency than in the control arm) were infusion-related reactions, neutropenia, thrombocytopenia, anemia, pyrexia, cough, and musculoskeletal disorder. The most common grade 3-4 adverse reactions (greater than or equal to 10%) were infusion-related reactions, neutropenia, and thrombocytopenia.
Infusion reactions occurred in 69% of patients receiving obinutuzumab; 21% experienced Grade 3 or 4 reactions. Symptoms (greater than 10%) included dyspnea, hypotension, nausea, vomiting, chills, flushing, and pyrexia.
Obinutuzumab is approved with a BOXED WARNING regarding Hepatitis B virus reactivation and Progressive Multifocal Leukoencephalopathy. Patients should be advised of these risks and assessed for Hepatitis B virus and reactivation risk. Infusion reactions are included in the WARNING and PRECAUTIONS section of the label.
The recommended dose and schedule for the approved regimen is:
Obinutuzumab:
Cycle 1: 100 mg intravenously on day 1, 900 mg on day 2, and 1000 mg on days 8 and 15.
Cycles 2-6: 1000 mg administered intravenously every 28 days
Chlorambucil:
0.5 mg/kg orally on days 1 and 15 of each cycle
Full prescribing information is available at:
http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/125486s000lbl.pdf
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).
GAZYVA(obinutuzumab)注射剂，为静脉输注
美国初次批准：2013
适应证和用途
GAZYVA(obinutuzumab)是一种针对CD20溶细胞抗体和适用于与苯丁酸氮芥[chlorambucil]联用，为有既往未治疗过慢性淋巴性白血病患者的治疗。(1，14)
剂量和给药方法
（1）用糖皮质激素，对乙酰氨基酚[acetaminophen]和抗组织胺预先给药。(2.2)
（2）为静脉输注稀释和给药。不要静脉推注或丸注。(2.1)
（3）对6个疗程推荐剂量(28天疗程)：
1）在疗程1第1天100 mg
2）在疗程1第2天900 mg
3）在疗程1第8和15天1000 mg
4）在疗程2-6第1天1000 mg (2.1)
剂型和规格
1000 mg/40mL (25 mg/mL)单次使用小瓶. (3)
禁忌证
无。
警告和注意事项
（1）输注反应：患者用糖皮质激素，对乙酰氨基酚和抗组织胺预先给药。输注期间严密监视. 对反应中断或终止输注。(2.2，5.3)
（2）肿瘤溶解综合征：预料肿瘤溶解综合征;用抗高尿酸血症药物预先给药和充分水化尤其是对有高肿瘤负荷和/或高循环淋巴细胞计数患者。纠正电解质异常，提供支持性医护和监视肾功能和液体平衡。(5.4)
（3）中性粒细胞减少：对感染监视。 (5.6)
（4）血小板减少：监视血细胞计数和出血。出血的处理可能需要血液制品支持。(5.7)
（5）免疫接种：不要给活病毒疫苗GAZYVA给予前或期间。(5.8)
不良事件
最常见不良事件(发生率 ≥10%)是：输注反应，中性粒细胞减少，血小板减少，贫血，发热，咳嗽，和肌肉骨骼疾病。(6)
