药品介绍
On December 15, 2008, the U. S. Food and Drug Administration approved plerixafor, solution for subcutaneous injection, (Mozobil, Genzyme Corp.) for use in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM).

The efficacy and safety of plerixafor in combination with G-CSF in NHL and MM were evaluated in two placebo-controlled studies (Studies 1 and 2).  Patients were randomized to receive either plerixafor 0.24 mg/kg or placebo each evening prior to apheresis. All patients received G-CSF 10 micrograms/kg daily for 4 days prior to the first dose of plerixafor or placebo and prior to apheresis.  Results from 298 patients with NHL from study 1 and 302 patients with MM from study 2 were analyzed.

In Study 1, 59% of patients with NHL who were mobilized with plerixafor and G-CSF collected > 5 X 106 CD34+ cells/kg from the peripheral blood in four or fewer apheresis sessions compared with 20% of patients who were mobilized with placebo and G-CSF (p < 0.001). The median number of days to reach > 5 x 106 CD34+ cells/kg was 3 days for the plerixafor group and not evaluable for the placebo group.
           
In Study 2, 72% of  patients with MM who were mobilized with plerixafor and G-CSF collected > 6 X 106 CD34+ cells/kg from the peripheral blood in two or fewer apheresis sessions compared with 34% of patients who were mobilized with placebo and G-CSF (p <0.001). The median number of days to reach > 6 x 106 CD34+ cells/kg was 1 day for the plerixafor group and 4 days for the placebo group.

Safety data for plerixafor in combination with G-CSF were obtained from 983 patients enrolled in 16 clinical studies (593 patients enrolled in randomized Studies 1 and 2 plus 410 patients enrolled in 14 additional non-randomized studies). Patients were primarily treated with plerixafor at daily doses of 0.24 mg/kg SC. Median exposure to plerixafor was 2 days (range 1 to 7 days).  The most common adverse reactions (> 10%) reported in patients who received plerixafor in conjunction with G-CSF that were more frequent than in patients who received placebo were diarrhea, nausea, fatigue, injection site reactions, headache, arthralgia, dizziness and vomiting. Prescribing physicians and patients should be aware of the potential for tumor cell mobilization in leukemia patients, increased circulating leukocytes and decreased platelet counts, splenic enlargement, and fetal harm when administered to pregnant women.

Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications

美国FDA批准plerixafor注射液上市

美国FDA 批准基Genzyme公司的plerixafor注射液（Mozobil）上市，与粒细胞集落刺激因子（G-CSF）联合用药促进红细胞生成素干细胞进入非霍奇金淋巴瘤（NHL）和多发性骨髓瘤（MM）患者血流以收集、随后自体移植。本品还被获准作为罕用药物。剂量规格普乐沙福20 mg/mL。

本品系一新颖的小分子CXCR4趋化因子受体阻断剂，在多项早期研究显示可快速有效地增加NHL和MM患者血液循环中的干细胞数。

本品在治疗需干细胞移植的某些类型癌症患者是一重大进展。由于本品有益于患者、医生和移植治疗中心将成为干细胞移植治疗方案的整体部分。

本品调动红细胞生成素干细胞从骨髓进入血流，收集、为需干细胞移植的某些类型癌症患者进行移植。以往，移植前患者需接受处方药化疗和（或）生长因子    类药物来帮助其调动红细胞生成素干细胞进入血流。一旦此细胞进入血流，它们被收集用于移植制备。

为了完成干细胞移植，按体重必需收集约200万个干细胞/kg。许多患者需3~4小时至数日来完成此过程。甚至一些患者调动不了足够的干细胞，因而不能进行移植。对许多癌症患者来说，调动干细胞是缩小癌症或治愈的唯一希望。

在本品关键的临床研究中，59％的NHL患者接受本品和G-CSF联合用药治疗旨在4个或更少的单采血液成分术期间内按体重至少收集的目标数为500万个干细胞/kg，与20％接受安慰剂的患者进行比较。Mozobil治疗组达到目标细胞数的平均天数为3日，安慰剂组未作评价。72％的MM患者接受Mozobil与G-CSF联合用药治疗旨在2个或更少的单采血液成分术期间内按体重至少收集的目标数为600万个干细胞/kg，与28％使用安慰剂患者进行对照。本品组达到靶细胞数的平均天数为1日，安慰剂组为4日。在关键的临床研究中选择的干细胞目标数是依据达到这些目标数有助于促进移植的文献资料。

本品除了有益于NHL和MM患者外，还为移植治疗中心带来了经济效益。本品可减少单采血液成分术的天数，可向移植中心提供可预测和有效地使用单采血液成分术中心。本品还可减少原先单一采用G-CSF治疗不能调动足够细胞数需第2次治疗的患者人数。

Indication(s):
In combination with granulocyte colony stimulating factor (G-CSF): To mobilize hematopoietic stem cells to the peripheral blood for collection and autologous transplantation in patients with non-Hodgkin's lymphoma or multiple myeloma.

Pharmacology:
Patient with non-Hodgkin's lymphoma or multiple myeloma may be candidates for autologous hematopoietic stem cell transplantation as part of their treatment. Before the transplant can take place, a minimum number of stem cells, generally about 2million/kg, must be collected. For some patients, this may be a lengthy process or may not occur satisfactorily at all. Plerixafor is a CXCR4 chemokine receptor antagonist that is designed to mobilize hematopoietic stem cells from the bone marrow to the bloodstream where they can be harvested, enabling certain patients to proceed to transplant. It blocks the binding of stromal cell-derived factor-1α, which, with CXCR4, plays a role in the homing and trafficking of stem cells in the bone marrow. Treatment with plerixafor causes increases in circulating leukocytes and stem cells.

Clinical Trials:
Two placebo-controlled studies were conducted to evaluate the safety and efficacy of plerixafor in combination with G-CSF for stem cell mobilization. In the first study, conducted in patients with non-Hodgkin's lymphoma, 59% of 150 patients given plerixafor + G-CSF collected ≥5x106 CD34+ cells/kg in four or fewer apheresis sessions, compared to 20% of 148 patients given placebo + G-CSF. In the second study, conducted in patients with multiple myeloma, 72% of 148 patients who were treated with plerixafor + G-CSF collected ≥6x106 CD34+ cells/kg from the peripheral blood in two or fewer apheresis sessions, compared with 34% of 154 patients given placebo + G-CSF. The target numbers of stem cells in the studies were chosen based on literature that suggests that reaching these targets can help to facilitate engraftment. Updated 12-month follow-up findings showed that graft durability rates for patients in the plerixafor + G-CSF and placebo + G-CSF arms were comparable.

Legal Classification:
Rx

Adults:
Start after 4 days' treatment with G-CSF. Give approximately 11 hours before starting apheresis. Repeat up to 4 consecutive days. Base dose on actual body weight. 0.24mg/kg SC; max 40mg/day. Renal impairment (CrCl≤50mL/min): 0.16mg/kg; max 27mg/day.

Children:
Not recommended.

Precaution(s):
Not for use in leukemia. May cause mobilization of tumor cells. Monitor blood and platelet counts (esp. neutrophils). Monitor for splenic rupture (eg, left upper quadrant/scapular or shoulder pain). Pregnancy (Cat.D); avoid. Nursing mothers: not recommended.

Interaction(s):
May be potentiated by drugs that reduce renal function or compete for active tubular secretion.

Adverse Reaction(s):
GI upset, fatigue, injection site reactions, headache, arthralgia, dizziness; tumor cell mobilization, increased circulating neutrophils, decreased platelet counts, enlarged spleen, vasovagal reaction may occur.

How Supplied:
Single-use vials (1.2mL)—1

Last Updated:

Mozobil（plerixafor注射液）；开发商Genzyme公司；于2008年12月被FDA批准用于非霍奇金淋巴瘤和多发性骨髓瘤的治疗。

Mozobil是一种造血干细胞激活剂以及CXCR4趋化因子拮抗剂。CXXR4属于特异性的基质细胞衍生因子1（SDF-1），SDF-1具有潜在的淋巴细胞趋化活性。由于SDF-1与CXCR4之间的相互作用对于造血干细胞停留在骨髓内具有非常重要的作用，所以能够阻断CXCR4受体的药物应该具有“动员”造血干细胞“释放”入血液的能力。Mozobil与粒细胞集落刺激因子（G-CSF）联合应用可将造血干细胞释放入周围血液中，收集后即可用于非霍奇金淋巴瘤和多发性骨髓瘤患者的自体移植。

Mozobil的剂型是注射液，用于皮下注射。接受Mozobil治疗前，患者需先给予G-CSF每天一次共4天。Mozobil最迟要在进行干细胞分离之前大约11个小时使用，最长可连续给药4天。推荐初始剂量为0.24 mg/kg，皮下注射。剂量不能超过40 mg/d。对于有中到重度肾损伤的患者（肌酐清除率 =50 mL/ min），Mozobil的剂量要减1/3，降到0.16 mg/kg。
FDA批准Mozobil上市是基于两项安慰剂对照临床研究的结果。两项研究中，均将患者分为两组，在进行干细胞分离的前一晚随机给予Mozobil 0.24 mg/kg或安慰剂。在首次给予Mozobil或安慰剂前以及进行干细胞分离的每个早上给予G-CSF 10 mg/kg共4天。

第一项研究：共入组298例非霍奇金淋巴瘤患者。结果表明，给予Mozobil和G-CSF联合治疗的患者，有59%的患者的外周血中可收集到≥ 5×106的CD34+ cells/kg，而用安慰剂和G-CSF的患者只有20%可收集到（P <0.001）。Mozobil组收集到5×106的CD34+ cells/kg的中位天数为3天。而安慰剂组没有达到中位时间。

第二项研究：入组了302例多发性多发性骨髓瘤患者。结果表明，给予Mozobil和G-CSF联合治疗的患者，有72%的患者可在外周血中收集到≥6×106的CD34+ cells/kg，而用安慰剂和G-CSF的患者只有34%可收集到（P <0.001）。Mozobil组收集到6×106的CD34+ cells/kg的中位天数为1天，安慰剂组为4天。

有关Mozobil长期安全性和有效性的研究正在进行中（3101-LTF），将历时5年，对患者的死亡结局以及疾病状态（复发或无病生存）进行评价。

不良反应主要包括：腹泻、恶心、乏力、注射部位反应、头痛、关节痛、头昏、呕吐等。

该药是一种造血干（祖）细胞激活剂，同时可刺激造血干（祖）细胞增殖、分化进入血液循环的功能。多项试验研究证明Mozobil在粒细胞刺激因子（G-CSF）或粒单核细胞刺激因子（GM-CSF）联合作用下，可使造血干（祖）细胞增殖，释放入外周血中的数量明显增多，使末梢血CD34+细胞群和造血祖细胞集落增加，可使自体造血干细胞移植的成功率明显增加。

由于非霍奇金淋巴瘤（NHL）和多发性骨髓瘤（MM）大部分缓解病例和进展病例需进行末梢血自体造血干细胞移植，而Mozobil联合G-CSF又能明显提高患者外周血中CD34+细胞的数量，大约可使60%病人的外周血CD34+细胞增加，保证了NHL和MM患者自体造血干细胞移植的成功。

FDA批准Mozobil用于造血干细胞移植 
 
Mozobil是一种提升造血干细胞数量的药物，2008年12月18日美国FDA批准该药用于造血干细胞移植。Mozobil多与粒细胞集落刺激因子（G-CSF）联合用于多发性骨髓瘤和非何杰金淋巴瘤患者，该类癌症患者在大剂量化（放）疗前有时需要采用血液分离术将造血干细胞分离储存备用，以便在化（放）疗后反输给病人。研究表明：相比单独使用G-CSF的癌症病人，同时使用MOZOBIL 和G-CSF能够在一定时间内收集到更多的造血干细胞。

Mozobil常见副作用有腹泻、恶心呕吐、疲乏、局部反应、头痛、关节痛、头昏等。
该药已批准由美国Genzyme公司生产。