Combined pegylated liposomal doxorubicin and bortezomib is highly effective in patients with recurrent or refractory multiple myeloma who received prior thalidomide/lenalidomide therapy
Combined pegylated liposomal doxorubicin and bortezomib is highly effective in patients with recurrent or refractory multiple myeloma who received prior thalidomide/lenalidomide therapy
复制标题
DOI：
10.1002/cncr.23326
复制
发表时间：
2008-04-01
期刊：
影响因子：
6.2
通讯作者：
Orlowski, Robert Z.
中科院分区：
文献类型：
--
作者：
Sonneveld, Pieter;Hajek, Roman;Orlowski, Robert Z.
背景最近，作者报告了在复发性/难治性多发性骨髓瘤患者中进行的一项III期随机试验中，与硼替佐米单药相比，聚乙二醇脂质体多柔比星（PLD）和硼替佐米联合治疗可改善疾病进展时间（TTP）。（MM）。在目前的分析中，他们确定了1）PLD+硼替佐米与硼替佐米单药治疗既往沙利度胺/来那度胺（免疫调节药物[IMiD]）治疗失败的MM患者的疗效，2）PLD+硼替佐米在IMiD暴露和IMiD初治患者中的疗效和安全性。该预先规定的分析包括646例患者，这些患者随机接受PLD联合硼替佐米（n = 324; 194例IMiD初治患者和130例IMiD暴露患者）或硼替佐米单药治疗（n = 322; 184例IMiD初治患者和138例IMiD暴露患者）。主要疗效终点为TTP，次要终点包括总生存期、缓解率和安全性。在IMiD暴露患者中，PLD+硼替佐米的中位TTP显著长于硼替佐米单药治疗（270天vs 205天）。未接受过IMiD治疗（295天）与接受PLD+硼替佐米治疗的IMiD暴露（270天）亚组之间的TTP无统计学差异。在总生存期分析中观察到支持联合治疗的持续趋势。在达到缓解的患者中，联合治疗组中IMiD初治患者和IMiD暴露患者的缓解持续时间相当，中位持续时间分别为310天和319天。PLD联合硼替佐米治疗3/4级不良事件的发生率相似，与既往IMiD治疗无关。尽管既往暴露于IMiD，但与硼替佐米单药治疗相比，PLD+硼替佐米联合治疗观察到TTP显著延长。对于IMiD初治和IMiD暴露亚组的联合治疗组，TTP相当。同样，PLD+硼替佐米组合的安全性特征未因既往IMiD暴露而改变。
BACKGROUND. Recently, the authors reported improved time to disease progression (TTP) with a combination of pegylated liposomal doxorubicin (PLD) and bortezomib compared with bortezomib alone in a phase 3 randomized trial in patients with recurrent/refractory multiple myeloma. (MM). In the current analysis, they determined 1) the efficacy of PLD plus bortezomib versus bortezomib alone in patients with MM who had failed on prior thalidomide/lenalidomide (immunomodulatory drug [IMiD]) treatment and 2) the efficacy and safety profile of PLD plus bortezomib in IMiD-exposed and IMiD-naive patients.METHODS. This prespecified analysis included 646 patients who were randomized to receive either PLD with bortezomib (n = 324; 194 IMiD-naive patients and 130 IMiD-exposed patients) or bortezomib alone (n = 322; 184 IMiD-naive patients and 138 IMiD-exposed patients). The primary efficacy endpoint was TTP, and secondary endpoints included overall survival, response rate, and safety.RESULTS. The median TTP was significantly longer with PLD plus bortezomib compared with bortezomib alone in IMiD-exposed patients (270 days vs 205 days). No statistical difference was noted with respect to TTP between IMiD-naive (295 days) versus IMiD-exposed (270 days) subgroups who received PLD plus bortezomib. A sustained trend favoring combination therapy was observed in analyses of overall survival. In patients who achieved a response, the response duration was comparable for IMiD-naive patients and IMiD-exposed patients in the combination treatment group and lasted a median of 310 days and 319 days, respectively. The incidence of grade 3/4 adverse events was similar with PLD plus bortezomib regardless of prior IMiD exposure.CONCLUSIONS. A significantly prolonged TTP was observed with combined PLD plus bortezomib combination therapy compared with bortezomib alone despite prior IMiD exposure. For the combination treatment arm in the IMiD-naive and IMiD-exposed subgroups, TTP was comparable. Similarly, the safety profile of the PLD plus bortezomib combination was unaltered by prior IMiD exposure.