文章：

伊沙佐米、环磷酰胺和地塞米松联合治疗既往未接受过治疗的有症状多发性骨髓瘤患者的1/2期试验

Phase 1/2 trial of ixazomib, cyclophosphamide and dexamethasone in patients with previously untreated symptomatic multiple myeloma

原文发布日期：2018-07-30

DOI: 10.1038/s41408-018-0106-3

类型: Article

开放获取: 是

英文摘要：

Ixazomib is the first oral proteasome inhibitor to enter the clinic. Given the efficacy of bortezomib in combination with cyclophosphamide and dexamethasone, we studied the combination of ixazomib, cyclophosphamide and dexamethasone (ICd) in newly diagnosed multiple myeloma (NDMM) and patients with measurable disease, irrespective of transplant eligibility, were enrolled. The phase 1 was to determine the maximum tolerated dose (MTD) of cyclophosphamide in the combination. Patients received ixazomib 4 mg (days 1, 8, 15), dexamethasone 40 mg (days 1, 8, 15, 22), and cyclophosphamide 300 or 400 mg/m2 days 1, 8, 15, 22; cycles were 28 days. We enrolled 51 patients, 10 in phase 1 and 41 patients in phase 2. The median age was 64.5 years (range: 41–88); 29% had high or intermediate risk FISH. The MTD was 400 mg/m2 of cyclophosphamide weekly. The best confirmed response in all 48 patients included ≥ partial response in 77%, including ≥ VGPR in 35%; 3 patients had a sCR. The response rate for all 48 evaluable patients at 4-cycles was 71%; the median time to response was 1.9 months. Common adverse events included cytopenias, fatigue and GI intolerance. ICd is a convenient, all oral combination that is well tolerated and effective in NDMM.

摘要翻译： 

伊沙佐米是首个进入临床的口服蛋白酶体抑制剂。基于硼替佐米联合环磷酰胺和地塞米松的疗效，我们研究了伊沙佐米联合环磷酰胺与地塞米松（ICd）方案在新诊断多发性骨髓瘤（NDMM）中的应用，不限移植适应症，纳入了存在可测量病灶的患者。1期研究旨在确定该联合方案中环磷酰胺的最大耐受剂量（MTD）。患者接受伊沙佐米4mg（第1、8、15天）、地塞米松40mg（第1、8、15、22天）及环磷酰胺300或400mg/m²（第1、8、15、22天）治疗，28天为一个周期。共纳入51例患者，其中1期10例，2期41例。中位年龄64.5岁（范围：41-88岁）；29%存在高危或中危FISH异常。环磷酰胺的周剂量MTD为400mg/m²。全部48例患者的最佳确认缓解率包括：部分缓解及以上77%，其中VGPR及以上35%；3例达到sCR。48例可评估患者在第4周期时总缓解率为71%，中位缓解时间为1.9个月。常见不良事件包括血细胞减少、疲劳和胃肠道不耐受。ICd是一种便捷的全口服联合方案，在新诊断多发性骨髓瘤中耐受性良好且疗效显著。

原文链接：

Phase 1/2 trial of ixazomib, cyclophosphamide and dexamethasone in patients with previously untreated symptomatic multiple myeloma