Engelhardt Monika, Wäsch Ralph, Reinhardt Heike, Kleber Martina
Hematology and Oncology, University of Freiburg, Hugstetterstr. 55, 79106, Freiburg, Germany,
Recent Results Cancer Res. 2014;201:359-72. doi: 10.1007/978-3-642-54490-3_22.
Pomalidomide (originally CC-4047 or 3-amino-thalidomide) is a derivative of thalidomide that is antiangiogenic and also acts as an immunomodulator. Pomalidomide, as the newest immunomodulatory agent (IMiD), has shown substantial in vitro antiproliferative and proapoptotic effects. In vivo studies have suggested limited cross-resistance between lenalidomide and pomalidomide, and the response of pomalidomide in relapsed and refractory (RR) multiple myeloma (MM) patients, including those who are refractory to both lenalidomide and bortezomib, has induced notable enthusiasm. Several studies have evaluated continuous (2 mg/day) or alternate (5 mg/2 day) dose schedules of pomalidomide, as well as 2 versus 4 mg schedules, and pomalidomide alone versus in combination with dexamethasone or other antimyeloma agents. Since pomalidomide plus low-dose dexamethasone has shown better responses, progression-free and overall survival than high-dose dexamethasone or pomalidomide alone, subsequent trials investigating pomalidomide combination therapy have been initiated. Among these trials combinations with alkylating agents (cyclophosphamide, bendamustin), anthracyclins (pegylated liposomal doxorubicin), proteasome inhibitors (bortezomib, carfilzomib), and various others can be found. Pomalidomide has also been assessed in AL amyloidosis, MPNs (myelofibrosis [MF]), Waldenstrom's macroglobulinemia, solid tumors (sarcoma, lung cancer), or HIV and--for AL amyloidosis and MF--has already proven remarkable activity. Due to its potency, pomalidomide was approved by the US Food and Drug Administration (FDA) for RRMM in 2/2013 and has also been approved by the European Medicines Agency (EMA).
泊马度胺（最初为CC - 4047或3 - 氨基沙利度胺）是沙利度胺的衍生物，具有抗血管生成作用，同时也是一种免疫调节剂。作为最新的免疫调节药物（IMiD），泊马度胺在体外显示出显著的抗增殖和促凋亡作用。体内研究表明来那度胺和泊马度胺之间的交叉耐药性有限，泊马度胺在复发和难治性（RR）多发性骨髓瘤（MM）患者中的反应，包括那些对来那度胺和硼替佐米均难治的患者，引起了显著的关注。多项研究评估了泊马度胺的持续（2毫克/天）或交替（5毫克/2天）给药方案，以及2毫克与4毫克的给药方案，还有泊马度胺单药治疗与联合地塞米松或其他抗骨髓瘤药物的治疗效果。由于泊马度胺联合低剂量地塞米松已显示出比高剂量地塞米松或泊马度胺单药治疗更好的反应、无进展生存期和总生存期，随后开展了研究泊马度胺联合治疗的试验。在这些试验中，可以找到与烷化剂（环磷酰胺、苯达莫司汀）、蒽环类药物（聚乙二醇化脂质体阿霉素）、蛋白酶体抑制剂（硼替佐米、卡非佐米）以及其他各种药物的联合方案。泊马度胺也已在AL淀粉样变性、骨髓增殖性肿瘤（MPN，骨髓纤维化[MF]）、华氏巨球蛋白血症、实体瘤（肉瘤、肺癌）或HIV中进行了评估，并且——对于AL淀粉样变性和MF——已证明具有显著活性。由于其有效性，泊马度胺于2013年2月被美国食品药品监督管理局（FDA）批准用于RRMM，并且也已获得欧洲药品管理局（EMA）的批准。
