A phase 2 trial of pomalidomide and dexamethasone rescue treatment in patients with AL amyloidosis
A phase 2 trial of pomalidomide and dexamethasone rescue treatment in patients with AL amyloidosis
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DOI：
10.1182/blood-2016-12-756528
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发表时间：
2017-04-13
期刊：
影响因子：
20.3
通讯作者：
Merlini, Giampaolo
中科院分区：
文献类型：
--
作者：
Palladini, Giovanni;Milani, Paolo;Merlini, Giampaolo
免疫调节药物是治疗轻链淀粉样变性的有效药物。然而，先前的研究并不能显示对泊马度胺抢救治疗有效的AL淀粉样变性患者的生存优势。在这项第二阶段的试验中，我们评估了泊马度胺和地塞米松(PDex)在AL淀粉样变性患者中的安全性和有效性，这些患者以前曾接触过硼替佐米、烷化剂和其他免疫调节药物。共有28名患者入选。3例患者接受泊马度胺2 mg/d治疗，无剂量限制性毒性。其余患者给予泊马度胺4 mg/d，持续给予泊马度胺，地塞米松20或40 mg，每周1次。15名患者经历了3到4级的不良反应；最常见的是液体滞留和感染。68%的患者观察到血液学反应(29%的患者部分或完全反应很好)，并改善了存活率。中位有效时间为1个月。PDex是一种快速有效的药物，可提高有反应的、经过大量预治疗的AL淀粉样变性患者的存活率。这项试验在www.Clinicaltrials.gov上注册为#NCT01510613。
Immunomodulatory drugs are active agents in light-chain (AL) amyloidosis. However, previous studies could not show a survival advantage for patients with AL amyloidosis responding to salvage treatment with pomalidomide. In this phase 2 trial, we assessed the safety and efficacy of pomalidomide and dexamethasone (PDex) in patients with AL amyloidosis who were previously exposed to bortezomib, alkylators, and other immunomodulatory drugs. Twenty-eight patients were enrolled. Three patients received pomalidomide 2 mg/d with no dose-limiting toxicity. The remaining patients received 4mg/d. Pomalidomide was administered continuously and dexamethasone was given once perweek at a dose of 20 or 40 mg. Fifteen patients experienced grade 3 to 4 adverse events; the most common were fluid retention and infection. Hematologic response was observed in 68% of patients (very good partial response or complete response in 29%), as well as improved survival. Median time to response was 1 month. PDex is a rapidly activere gimen and improves survival in responding, heavily pretreated patients with AL amyloidosis. This trial was registered at www.clinicaltrials.gov as #NCT01510613.