文章：

基于IMiD的试验在免疫球蛋白轻链淀粉样变性患者中的长期结局：一项汇总分析

Long-term outcomes of IMiD-based trials in patients with immunoglobulin light-chain amyloidosis: a pooled analysis

原文发布日期：2020-01-08

DOI: 10.1038/s41408-019-0266-9

类型: Article

开放获取: 是

英文摘要：

Rarity of light-chain amyloidosis (AL) makes randomized studies challenging. We pooled three phase II studies of immunomodulatory drugs (IMiDs) to update survival, toxicity, and assess new response/progression criteria. Studies included were lenalidomide-dexamethasone (Len-Dex) (n = 37; years: 2004–2006), cyclophosphamide-Len-Dex (n = 35; years: 2007–2008), and pomalidomide-Dex (n = 29; years: 2008–2010) trial. Primary endpoint was hematologic response. Overall survival (OS) was calculated from registration to death and progression-free survival (PFS) was calculated from registration to progression or death. Hematologic, cardiac, and renal response/progression was assessed using the modern criteria. Analysis included 101 patients, with a median age of 65 years, 61% male, 37 newly diagnosed (ND), and 64 relapsed/refractory (RR). Median follow-up was 101 months (range 17–150) and 78% of patients died. OS and PFS for pooled cohort were 31 and 15 months, respectively. Forty-eight patients achieved a hematologic response; for ND, 10 patients (28%) achieved ≥VGPR (very good partial response) and 8 (14%) among the RR. Only cardiac stage was prognostic for OS. Common grade ≥3 toxicities were hematologic, fatigue, and rash, and were similar among studies. Hematologic and renal responses occurred more frequently and rapidly using modern response criteria; cardiac response was less frequent but occurred quickly. IMiDs can result in long progression-free intervals/survival with tolerable toxicities. The new response/progression criteria were rapid and allows for tailoring therapy.
 

摘要翻译： 

轻链淀粉样变性（AL）的罕见性使得随机研究面临挑战。我们汇总了三项免疫调节药物（IMiDs）的II期研究，以更新生存期和毒性数据，并评估新的缓解/进展标准。纳入的研究包括来那度胺-地塞米松（Len-Dex）试验（n=37；年份：2004-2006）、环磷酰胺-来那度胺-地塞米松（Cyclophosphamide-Len-Dex）试验（n=35；年份：2007-2008）和泊马度胺-地塞米松（Pomalidomide-Dex）试验（n=29；年份：2008-2010）。主要终点为血液学缓解。总生存期（OS）从注册时计算至死亡，无进展生存期（PFS）从注册时计算至疾病进展或死亡。采用现代标准评估血液学、心脏和肾脏的缓解/进展情况。分析共纳入101例患者，中位年龄65岁，61%为男性，其中37例为新诊断（ND），64例为复发/难治性（RR）。中位随访时间为101个月（范围17-150），78%的患者死亡。汇总队列的中位OS和PFS分别为31个月和15个月。48例患者实现血液学缓解；ND患者中10例（28%）达到≥VGPR（非常好的部分缓解），RR患者中8例（14%）达到≥VGPR。仅心脏分期对OS具有预后意义。常见的≥3级毒性反应包括血液学毒性、疲劳和皮疹，各研究间结果相似。采用现代缓解标准后，血液学和肾脏缓解的发生更频繁且更迅速；心脏缓解较少见但发生迅速。IMiDs可在可耐受毒性下实现长期无进展间期/生存。新的缓解/进展标准评估快速，有助于个体化治疗调整。

原文链接：

Long-term outcomes of IMiD-based trials in patients with immunoglobulin light-chain amyloidosis: a pooled analysis