Office of Oncology Drug Products, Office of New Drugs, Michael Brave U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20903, USA.
Oncology. 2010;78(3-4):282-8. doi: 10.1159/000315736. Epub 2010 Jun 8.
On December 15, 2008, the US Food and Drug Administration approved plerixafor (Mozobil; Genzyme Corp.), a new small-molecule inhibitor of the CXCR4 chemokine receptor, for use in combination with granulocyte colony-stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSC) to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). This summary reviews the database supporting this approval.
The safety and efficacy of plerixafor were demonstrated by 2 multicenter, randomized, placebo-controlled studies in patients with NHL and MM who were eligible for autologous HSC transplantation. The primary efficacy end points were the collection of > or = 5 x 10(6) CD34+ cells/kg from the peripheral blood in 4 or fewer apheresis sessions in patients with NHL or > or = 6 x 10(6) CD34+ cells/kg from the peripheral blood in 2 or fewer apheresis sessions in patients with MM.
The 2 randomized studies combined enrolled 600 patients (298 with NHL and 302 with MM). Fifty-nine percent of patients with NHL who were mobilized with G-CSF and plerixafor had peripheral blood HSC collections of > or = 5 x 10(6) CD34+ cells/kg in 4 or fewer apheresis sessions, compared with 20% of patients with NHL who were mobilized with G-CSF and placebo (p < 0.001). Seventy-two percent of patients with MM who were mobilized with Mozobil and G-CSF had peripheral blood HSC collections of > or = 6 x 10(6) CD34+ cells/kg in 2 or fewer apheresis sessions, compared with 34% of patients with MM who were mobilized with placebo and G-CSF (p < 0.001). Common adverse reactions included diarrhea, nausea, vomiting, flatulence, injection site reactions, fatigue, arthralgia, headache, dizziness, and insomnia.
This report describes the Food and Drug Administration review supporting the approval of plerixafor.
2008 年 12 月 15 日，美国食品和药物管理局批准了plerixafor（ Mozobil；Genzyme 公司），一种 CXCR4 趋化因子受体的新型小分子抑制剂，与粒细胞集落刺激因子（G-CSF）联合使用，以动员造血干细胞（HSC）进入外周血进行收集，并随后在非霍奇金淋巴瘤（NHL）和多发性骨髓瘤（MM）患者中进行自体移植。本总结回顾了支持这一批准的数据库。
plerixafor 的安全性和有效性通过 2 项多中心、随机、安慰剂对照研究在符合自体 HSC 移植条件的 NHL 和 MM 患者中得到证实。主要疗效终点是 NHL 患者在外周血中采集≥5×10(6)个 CD34+细胞/kg，4 次或更少的单采，或 MM 患者在外周血中采集≥6×10(6)个 CD34+细胞/kg，2 次或更少的单采。
这两项随机研究共纳入 600 例患者（298 例 NHL 和 302 例 MM）。用 G-CSF 和 plerixafor 动员的 NHL 患者中有 59%在外周血中采集≥5×10(6)个 CD34+细胞/kg，4 次或更少的单采，而用 G-CSF 和安慰剂动员的 NHL 患者中只有 20%（p<0.001）。用 Mozobil 和 G-CSF 动员的 MM 患者中有 72%在外周血中采集≥6×10(6)个 CD34+细胞/kg，2 次或更少的单采，而用安慰剂和 G-CSF 动员的 MM 患者中只有 34%（p<0.001）。常见的不良反应包括腹泻、恶心、呕吐、气胀、注射部位反应、疲劳、关节痛、头痛、头晕和失眠。
本报告描述了美国食品和药物管理局对 plerixafor 批准的审查。
