文章：

口服伊沙佐米-地塞米松对比口服泊马度胺-地塞米松治疗来那度胺难治、蛋白酶体抑制剂暴露过的多发性骨髓瘤：一项随机 II 期试验

Oral ixazomib-dexamethasone vs oral pomalidomide-dexamethasone for lenalidomide-refractory, proteasome inhibitor-exposed multiple myeloma: a randomized Phase  2 trial

原文发布日期：2022-01-24

DOI: 10.1038/s41408-021-00593-2

类型: Article

开放获取: 是

英文摘要：

Multiple myeloma (MM) patients typically receive several lines of combination therapy and first-line treatment commonly includes lenalidomide. As patients age, they become less tolerant to treatment, requiring convenient/tolerable/lenalidomide-free options. Carfilzomib and/or bortezomib-exposed/intolerant, lenalidomide-refractory MM patients with ≥2 prior lines of therapy were randomized 3:2 to ixazomib-dexamethasone (ixa-dex) (n = 73) or pomalidomide-dexamethasone (pom-dex) (n = 49) until progression/toxicity. Median progression-free survival (mPFS) was 7.1 vs 4.8 months with ixa-dex vs pom-dex (HR 0.847, 95% CI 0.535–1.341, P = 0.477; median follow-up: 15.3 vs 17.3 months); there was no statistically significant difference between arms. In patients with 2 and ≥3 prior lines of therapy, respectively, mPFS was 11.0 vs 5.7 months (HR 1.083, 95% CI 0.547–2.144) and 5.7 vs 3.7 months (HR 0.686, 95% CI 0.368–1.279). Among ixa-dex vs pom-dex patients, 69% vs 81% had Grade ≥3 treatment-emergent adverse events (TEAEs), 51% vs 53% had serious TEAEs, 39% vs 36% had TEAEs leading to drug discontinuation, 44% vs 32% had TEAEs leading to dose reduction, and 13% vs 13% died on study. Quality of life was similar between arms and maintained during treatment. Ixa-dex represents an important lenalidomide-free, oral option for this heavily pretreated, lenalidomide-refractory, proteasome inhibitor-exposed population. Trial registration: ClinicalTrials.gov number, NCT03170882.
 

摘要翻译： 

多发性骨髓瘤（MM）患者通常接受多线联合治疗，一线治疗常包含来那度胺。随着年龄增长，患者对治疗的耐受性降低，需要便捷/可耐受/不含来那度胺的治疗选择。本研究针对既往接受过≥2线治疗、且暴露于卡非佐米和/或硼替佐米或不耐受、对来那度胺耐药的MM患者，按3:2随机分配至伊沙佐米-地塞米松组（ixa-dex）（n=73）或泊马度胺-地塞米松组（pom-dex）（n=49），持续治疗至疾病进展或出现毒性反应。中位无进展生存期（mPFS）在ixa-dex组与pom-dex组分别为7.1个月 vs 4.8个月（HR 0.847，95% CI 0.535–1.341，P=0.477；中位随访时间：15.3个月 vs 17.3个月）；两组间无统计学显著差异。在既往接受过2线和≥3线治疗的患者中，mPFS分别为11.0个月 vs 5.7个月（HR 1.083，95% CI 0.547–2.144）和5.7个月 vs 3.7个月（HR 0.686，95% CI 0.368–1.279）。ixa-dex组与pom-dex组中，≥3级治疗期间出现的不良事件（TEAEs）发生率分别为69% vs 81%，严重TEAEs为51% vs 53%，导致停药的不良事件为39% vs 36%，导致剂量降低的不良事件为44% vs 32%，研究中死亡率为13% vs 13%。两组生活质量相近且在治疗期间保持稳定。对于这类经过大量预处理、对来那度胺耐药且暴露于蛋白酶体抑制剂的患者群体，伊沙佐米-地塞米松方案是一种重要的口服、不含来那度胺的治疗选择。试验注册号：ClinicalTrials.gov NCT03170882。

原文链接：

Oral ixazomib-dexamethasone vs oral pomalidomide-dexamethasone for lenalidomide-refractory, proteasome inhibitor-exposed multiple myeloma: a randomized Phase  2 trial