Department of Hematology, General Hospital of Beijing Military Area of PLA, Beijing, People's Republic of China.
Onco Targets Ther. 2014 Sep 10;7:1593-9. doi: 10.2147/OTT.S67165. eCollection 2014.
Multiple myeloma (MM) is a clonal malignancy characterized by the proliferation of malignant plasma cells in the bone marrow and the production of monoclonal immunoglobulin. Although some newly approved drugs (thalidomide, lenalidomide, and bortezomib) demonstrate significant benefit for MM patients with improved survival, all MM patients still relapse. Arsenic trioxide (ATO) is the most active single agent in acute promyelocytic leukemia, the antitumor activity of which is partly dependent on the production of reactive oxygen species. Due to its multifaceted effects observed on MM cell lines and primary myeloma cells, Phase I/II trials have been conducted in heavily pretreated patients with relapsed or refractory MM. Therapy regimens varied dramatically as to the dosage of ATO and monotherapy versus combination therapy with other agents available for the treatment of MM. Although ATO-based combination treatment was well tolerated by most patients, most trials found that ATO has limited effects on MM patients. However, since small numbers of patients were randomized to different treatment arms, trials have not been statistically powered to determine the differences in progression-free survival and overall survival among the experimental arms. Therefore, large Phase III studies of ATO-based randomized controlled trials will be needed to establish whether ATO has any potential beneficial effects in the clinical setting.
多发性骨髓瘤（MM）是一种克隆性恶性肿瘤，其特征是骨髓中恶性浆细胞的增殖和单克隆免疫球蛋白的产生。尽管一些新批准的药物（沙利度胺、来那度胺和硼替佐米）显示出对改善 MM 患者生存的显著益处，但所有 MM 患者仍会复发。三氧化二砷（ATO）是急性早幼粒细胞白血病中最有效的单一药物，其抗肿瘤活性部分依赖于活性氧的产生。由于其对 MM 细胞系和原代骨髓瘤细胞的多方面作用，已在复发或难治性 MM 的大量预处理患者中进行了 I/II 期试验。ATO 的剂量以及单药治疗与其他可用于治疗 MM 的药物联合治疗的方案因试验而异。尽管基于 ATO 的联合治疗被大多数患者耐受良好，但大多数试验发现 ATO 对 MM 患者的作用有限。然而，由于不同治疗组的患者数量较少，试验没有统计学能力来确定实验组之间无进展生存期和总生存期的差异。因此，需要进行基于 ATO 的大型 III 期随机对照试验，以确定 ATO 在临床环境中是否具有任何潜在的有益效果。
