文章：

I/II期苯达莫司汀、伊沙佐米和地塞米松治疗复发/难治性多发性骨髓瘤的临床试验

Phase I/II trial of bendamustine, ixazomib, and dexamethasone in relapsed/refractory multiple myeloma

原文发布日期：2019-07-29

DOI: 10.1038/s41408-019-0219-3

类型: Article

开放获取: 是

英文摘要：

In this phase I/II trial, BID, bendamustine (70, 80, or 90 mg/m2), ixazomib (4 mg), and dexamethasone (40 mg), was administered to 28 patients with relapsed and/or refractory multiple myeloma (RRMM) exposed to bortezomib and lenalidomide and refractory to at least one. A 3 + 3 dose escalation based on dose-limiting toxicities (DLTs) was employed in phase I (total 15); 2/6 patients developed DLTs (neutropenia and thrombocytopenia) at dose level 3 establishing the recommended phase II dose as bendamustine 80 mg/m2, ixazomib 4 mg, and dexamethasone 40 mg. The median age was 67 years (range, 42–72), and 43% were females. Patients received a median of 4 (range, 4–9) prior lines of therapy, of which ~50% were double refractory. In phase II, total 19 patients were treated. With a median follow-up of 17 months, 11% achieved very good partial response, 50% achieved partial response, and 27% achieved stable disease. Median progression free (PFS) and overall (OS) survival were 5.2 months (95% CI, 1.96–8.3) and 23.2 months (95% CI 16.3–30.07). The most frequent adverse events were anemia, thrombocytopenia, leukopenia, nausea, diarrhea, and infections. Peripheral neuropathy was infrequent. BID is a well-tolerated and effective combination therapy for patients with RRMM.
 

摘要翻译： 

在这项I/II期临床试验中，28名曾接受硼替佐米和来那度胺治疗且至少对一种药物耐药的复发/难治性多发性骨髓瘤患者接受了BID方案治疗。该方案包括苯达莫司汀、伊沙佐米和地塞米松。I期阶段采用基于剂量限制毒性（DLT）的3+3剂量递增设计，在剂量水平3时，2/6患者出现DLT，最终确定II期推荐剂量为苯达莫司汀80mg/m²、伊沙佐米4mg、地塞米松40mg。入组患者中位年龄67岁，43%为女性，既往中位治疗线数为4线，约50%为双重耐药患者。II期阶段共治疗19例患者，中位随访17个月后，11%达到非常好的部分缓解，50%达到部分缓解，27%实现疾病稳定。中位无进展生存期和总生存期分别为5.2个月和23.2个月。最常见不良事件包括贫血、血小板减少、白细胞减少、恶心、腹泻和感染，周围神经病变发生率较低。研究表明BID方案是RRMM患者耐受性良好且有效的联合治疗方案。

原文链接：

Phase I/II trial of bendamustine, ixazomib, and dexamethasone in relapsed/refractory multiple myeloma