Adis, a Wolters Kluwer Business, Auckland, New Zealand.
Drugs. 2011 Aug 20;71(12):1623-47. doi: 10.2165/11206040-000000000-00000.
Plerixafor (Mozobil®) is a CXCR4 chemokine receptor antagonist that is indicated for use in combination with granulocyte colony-stimulating factor (G-CSF) to mobilize stem cells to the peripheral blood for collection and subsequent autologous stem-cell transplantation in patients who have non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM) [US] and in patients who have lymphoma or MM and are poor mobilizers (EU). This article reviews the clinical efficacy and tolerability of subcutaneous plerixafor for stem-cell mobilization in patients with lymphoma or MM, as well as summarizing its pharmacological properties. Pharmacoeconomic analyses of plerixafor and decision-making algorithms intended to optimize its use are also discussed. Plerixafor plus G-CSF mobilized stem cells more efficiently than placebo plus G-CSF in adults with NHL or MM, according to the results of two randomized, double-blind, multicentre trials. In these trials, significantly more plerixafor plus G-CSF recipients than placebo plus G-CSF recipients reached primary apheresis targets in significantly fewer apheresis days. In the trial in patients with NHL, significantly more plerixafor plus G-CSF than placebo plus G-CSF recipients proceeded to transplantation. Results of compassionate-use studies in patients with lymphoma or MM demonstrated that plerixafor plus G-CSF successfully mobilized stem cells in the majority of patients who were poor mobilizers (i.e. sufficient CD34+ cells had not been collected during apheresis or apheresis had not occurred because of low peripheral blood CD34+ cell counts). Results of compassionate-use studies and additional studies in patients with lymphoma or MM also demonstrated that plerixafor plus G-CSF successfully mobilized stem cells in predicted poor mobilizers, such as heavily pretreated patients considered to be at high risk of mobilization failure. In addition, a small study showed mobilization with pre-emptive plerixafor to be effective. Subcutaneous plerixafor was generally well tolerated during stem-cell mobilization in patients with NHL or MM; the most commonly occurring treatment-related adverse events in plerixafor plus G-CSF recipients included injection-site reactions and gastrointestinal adverse events. Preliminary results of a US cost-effectiveness analysis suggest that plerixafor plus G-CSF is a cost-saving option compared with cyclophosphamide plus G-CSF. A retrospective US cost analysis found no significant difference between plerixafor plus G-CSF and cyclophosphamide plus G-CSF recipients in the median total cost of initial mobilization, suggesting that the cost of plerixafor may be offset by increased utilization of other resources in patients receiving alternative mobilization regimens. Additional cost analyses examined the use of pre-emptive plerixafor; institutions have developed decision-making algorithms, mainly relating to the use of pre-emptive plerixafor, to help optimize its use. In conclusion, plerixafor is a valuable stem-cell mobilizer for use in combination with G-CSF in patients with lymphoma or MM, particularly in patients who are poor mobilizers or predicted poor mobilizers.
培洛昔福（Mozobil®）是一种趋化因子受体 CXCR4 拮抗剂，适用于联合粒细胞集落刺激因子（G-CSF）动员造血干细胞进入外周血，以便采集，随后对患有非霍奇金淋巴瘤（NHL）或多发性骨髓瘤（MM）[美国]的患者，或患有淋巴瘤或 MM 且动员效果不佳的患者（欧盟）进行自体干细胞移植。本文综述了培洛昔福在淋巴瘤或 MM 患者中进行干细胞动员的临床疗效和耐受性，并总结了其药理学特性。还讨论了培洛昔福的药物经济学分析和旨在优化其使用的决策算法。两项随机、双盲、多中心试验的结果表明，培洛昔福联合 G-CSF 比安慰剂联合 G-CSF 更有效地动员 NHL 或 MM 成年患者的干细胞。在这些试验中，与安慰剂联合 G-CSF 相比，更多的培洛昔福联合 G-CSF 接受者在更少的采集天数内达到了主要采集目标。在 NHL 患者的试验中，与安慰剂联合 G-CSF 相比，更多的培洛昔福联合 G-CSF 接受者进行了移植。在淋巴瘤或 MM 患者的同情使用研究中结果表明，培洛昔福联合 G-CSF 成功动员了大多数动员效果不佳的患者（即采集过程中未采集到足够的 CD34+细胞，或由于外周血 CD34+细胞计数低而未进行采集）的干细胞。在淋巴瘤或 MM 患者的同情使用研究和其他研究的结果还表明，培洛昔福联合 G-CSF 成功动员了预测的动员效果不佳的患者的干细胞，如被认为动员失败风险较高的大量预处理患者。此外，一项小型研究表明，抢先使用培洛昔福进行动员是有效的。在 NHL 或 MM 患者的干细胞动员过程中，培洛昔福通常具有良好的耐受性；培洛昔福联合 G-CSF 接受者中最常见的治疗相关不良事件包括注射部位反应和胃肠道不良事件。美国一项成本效益分析的初步结果表明，与环磷酰胺联合 G-CSF 相比，培洛昔福联合 G-CSF 是一种节省成本的选择。一项美国回顾性成本分析发现，在初始动员的总中位成本方面，培洛昔福联合 G-CSF 与环磷酰胺联合 G-CSF 接受者之间没有显著差异，这表明培洛昔福的成本可能会因接受替代动员方案的患者更多地利用其他资源而得到弥补。其他成本分析研究了抢先使用培洛昔福的情况；各机构制定了决策算法，主要涉及抢先使用培洛昔福，以帮助优化其使用。总之，培洛昔福是一种有价值的造血干细胞动员剂，与 G-CSF 联合用于淋巴瘤或 MM 患者，特别是动员效果不佳或预测动员效果不佳的患者。
