Hanaizi Zahra, Flores Beatriz, Hemmings Robert, Camarero Jorge, Sancho-Lopez Arantxa, Salmonson Tomas, Gisselbrecht Christian, Laane Edward, Pignatti Francesco
European Medicines Agency, London, United Kingdom; Medicines and Healthcare Products Regulatory Agency, London, United Kingdom; Agencia Española de Medicamentos y Productos Sanitarios, Madrid, Spain; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Hôpital Saint Louis, Paris, France; North Estonia Regional Hospital, Tallinn, Estonia
European Medicines Agency, London, United Kingdom; Medicines and Healthcare Products Regulatory Agency, London, United Kingdom; Agencia Española de Medicamentos y Productos Sanitarios, Madrid, Spain; Läkemedelsverket, Medical Products Agency, Uppsala, Sweden; Hôpital Saint Louis, Paris, France; North Estonia Regional Hospital, Tallinn, Estonia.
Oncologist. 2015 Mar;20(3):329-34. doi: 10.1634/theoncologist.2014-0073. Epub 2015 Feb 11.
On August 5, 2013, a marketing authorization valid throughout the European Union (EU) was issued for pomalidomide in combination with dexamethasone for the treatment of adult patients with relapsed and refractory multiple myeloma (MM) who have received at least two prior treatment regimens, including both lenalidomide and bortezomib, and have demonstrated disease progression on the last therapy. Pomalidomide is an immunomodulating agent. The recommended starting dose of pomalidomide is 4 mg once daily taken on days 1-21 of repeated 28-day cycles. The main evidence of efficacy for pomalidomide in MM was based on a phase III multicenter, randomized, open-label study (CC-4047-MM-003) in which pomalidomide plus low-dose dexamethasone therapy (POM+LoDEX) was compared with high-dose dexamethasone alone (HiDEX) in previously treated adult patients with relapsed and refractory multiple myeloma who had received at least two prior treatment regimens, including both lenalidomide and bortezomib, and had demonstrated disease progression on the last therapy. For the intent-to-treat population, median progression-free survival based on International Myeloma Working Group criteria was 15.7 weeks (95% confidence interval [CI]: 13.0-20.1) in the POM+LoDEX group versus 8.0 weeks (95% CI: 7.0-9.0) in the HiDEX group (log-rank p value <.001). Overall survival (secondary endpoint) was also different in the two treatment groups (hazard ratio 0.53 [95% CI: 0.37-0.74]). The most commonly reported adverse reactions to pomalidomide in clinical studies were anemia (45.7%), neutropenia (45.3%) and thrombocytopenia (27%), fatigue (28.3%), pyrexia (21%), peripheral edema (13%), and infections including pneumonia (10.7%). Peripheral neuropathy adverse reactions were reported in 12.3% of patients, and venous embolic or thrombotic (VTE) adverse reactions were reported in 3.3% of patients. Pomalidomide is expected to be teratogenic. This paper summarizes the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the EMA website (http://www.ema.europa.eu).
2013年8月5日，泊马度胺联合地塞米松被授予一项在整个欧盟（EU）范围内有效的上市许可，用于治疗复发和难治性多发性骨髓瘤（MM）的成年患者，这些患者此前至少接受过两种治疗方案，包括来那度胺和硼替佐米，并且在最后一次治疗中已出现疾病进展。泊马度胺是一种免疫调节剂。泊马度胺的推荐起始剂量为每日4毫克，在重复的28天周期的第1 - 21天服用。泊马度胺治疗MM的主要疗效证据基于一项III期多中心、随机、开放标签研究（CC - 4047 - MM - 003），该研究将泊马度胺加低剂量地塞米松疗法（POM + LoDEX）与单独使用高剂量地塞米松（HiDEX）相比较，受试对象为既往接受过至少两种治疗方案（包括来那度胺和硼替佐米）且在最后一次治疗中已出现疾病进展的复发和难治性多发性骨髓瘤成年患者。对于意向性治疗人群，根据国际骨髓瘤工作组标准，POM + LoDEX组的中位无进展生存期为15.7周（95%置信区间[CI]：13.0 - 20.1），而HiDEX组为8.0周（95% CI：7.0 - 9.0）（对数秩p值 <.001）。两个治疗组的总生存期（次要终点）也存在差异（风险比0.53 [95% CI：0.37 - 0.74]）。临床研究中报告的泊马度胺最常见不良反应为贫血（45.7%）、中性粒细胞减少（45.3%）和血小板减少（27%）、疲劳（28.3%）、发热（21%）、外周水肿（13%）以及包括肺炎在内的感染（10.7%）。12.3%的患者报告有外周神经病变不良反应，3.3%的患者报告有静脉栓塞或血栓形成（VTE）不良反应。泊马度胺预计具有致畸性。本文总结了该申请在欧盟获批的科学审评情况。详细的科学评估报告和产品信息，包括产品特性摘要，可在欧洲药品管理局网站（http://www.ema.europa.eu）获取。
