FDA批准奥法木单抗用于慢性淋巴细胞白血病治疗

美国食品药品管理局（FDA）已批准奥法木单抗（Arzerra静脉输液剂）联合苯丁酸氮芥，用于不适合以氟达拉滨为基础治疗的慢性淋巴细胞白血病（CCL）未治患者。

奥法木单抗是靶向抗CD20单克隆抗体，由葛兰素史克（GSK）生产，最初于2009年获得加速批准。作为这一批准的条件，FDA要求GSK开展进一步临床研究。试验结果满足了上市后要求，也成为4月17日批准令的依据。至此，奥法木单抗的批准由加速批准转变为常规批准。

这项多中心随机开放试验比较了奥法木单抗联合苯丁酸氮芥治疗与苯丁酸氮芥单独治疗的有效性和安全性。患者按下述方案静注奥法木单抗：第1疗程第1天300 mg，第8天1,000 mg，后续所有疗程的第1天均为1,000 mg，28天为1个疗程。两组患者均在每个疗程的第1~7天口服10 mg/m的苯丁酸氮芥。奥法木单抗治疗患者预先给予对乙酰氨基酚、抗组胺药物和糖皮质激素药物。

奥法木单抗联合用药组中位无进展生存期为22.4个月，而苯丁酸氮芥单独治疗为13.1个月。无进展生存期由独立审查委员会依据2008年CCL国际研讨会更新后的美国癌症研究所工作组指南进行盲法评估。

奥法木单抗联合苯丁酸氮芥治疗最常见不良反应为输液反应、中性粒细胞减少症、乏力、头痛、白细胞减少症、单纯性疱疹、下呼吸道感染、关节痛以及上腹部疼痛。67%的奥法木单抗治疗患者出现1种或以上输液反应，10%的患者出现3级或以上输液反应。

去年9月，FDA在奥法木单抗说明书中添加了一项有关乙肝感染患者病毒感染再激活风险的黑框警告。

FDA称，对于CCL未治患者，推荐剂量和方案为：第1疗程第1天300 mg，第8天1,000 mg，后续所有疗程的第1天均为1,000 mg，28天为1个疗程，最少3个疗程，直到达到最佳应答或最大为12个疗程。

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By: ALICIA AULT, Pediatric News Digital Network

The Food and Drug Administration has approved ofatumumab (Arzerra injection, for intravenous infusion) in combination with chlorambucil, for previously untreated patients with chronic lymphocytic leukemia for whom fludarabine-based therapy is considered inappropriate.

Ofatumumab, an anti-CD20-directed monoclonal antibody, manufactured by GlaxoSmithKline, was originally given an accelerated approval in 2009. As a condition of that approval, the company was required to conduct further studies. The trial used as the basis of the April 17 approval fulfilled that postmarketing requirement, and accelerated approval was converted to regular approval, said the FDA.

That multicenter, randomized, open-label trial compared ofatumumab in combination with chlorambucil to chlorambucil alone. Patients received an intravenous infusion of ofatumumab on the following schedule: 300 mg on cycle 1, day 1; 1,000 mg on cycle 1, day 8; and 1,000 mg on day 1 of all subsequent 28-day cycles. In both arms, chlorambucil was given at a dose of 10 mg/meter orally on days 1 to 7, every 28 days. Ofatumumab patients were premedicated with acetaminophen, an antihistamine, and a glucocorticoid.

Median progression-free survival was 22.4 months for patients receiving the combination, compared with 13.1 months for those who were given chlorambucil alone. Progression-free survival was assessed by a blinded independent review committee using the 2008 International Workshop on Chronic Lymphocytic Leukemia update of the National Cancer Institute Working Group guidelines.

The most common adverse reactions of the ofatumumab-chlorambucil combination were infusion reactions, neutropenia, asthenia, headache, leukopenia, herpes simplex, lower respiratory tract infection, arthralgia, and upper abdominal pain. Sixty-seven percent of patients who received ofatumumab experienced one or more symptoms of infusion reaction; 10% experienced a grade 3 or greater infusion reaction.

In September, the FDA added a black box warning to ofatumumab’s label on the risk of reactivation of hepatitis B virus infection in patients with prior infection.

For previously untreated chronic lymphocytic leukemia, the recommended dose and schedule is 300 mg on day 1; followed 1 week later by 1,000 mg on day 8; followed by 1,000 mg on day 1 of subsequent 28-day cycles for a minimum of 3 cycles until best response or a maximum of 12 cycles, according to the FDA.