文章：

联合使用卡非佐米和帕比司他治疗复发/难治性多发性骨髓瘤：多发性骨髓瘤研究联盟Ⅰ期研究结果

Combining carfilzomib and panobinostat to treat relapsed/refractory multiple myeloma: results of a Multiple Myeloma Research Consortium Phase I Study

原文发布日期：2019-01-04

DOI: 10.1038/s41408-018-0154-8

类型: Article

开放获取: 是

英文摘要：

Proteasome (PIs) and hystone deacetylase inhibitors (HDACis) have previously shown synergistic activity in the treatment of relapesed/refractory multiple myeloma (RRMM) patients. In this phase 1 study, we combined carfilzomib, a second generation PI, with panobinostat, a HDACi, to determine the maximum tolerated dose (MTD) of the combination (CarPan) and assess safety and efficacy among RRMM patients. Thirty-two patients (median of 4 prior lines of therapy) were enrolled. The MTD was carfilzomib 36 mg/m2 (on days 1, 2, 8, 9, 15, and 16) and panobinostat 20 mg (TIW, 3 weeks on/1 week off, every 28 days), administered until progression. At the MTD, the most common grade 3/4, treatment-related adverse events were thrombocytopenia (41%), fatigue (17%), and nausea/vomiting (12%). The objective response rate (ORR) and clinical benefit rate were 63% and 68%, respectively. Median progression-free survival (PFS) and overall survival (OS) for the entire population were 8 and 23 months, respectively. No differences in terms of ORR (55% vs. 57%), median PFS (months 8 vs. 7 months) and OS (24 vs. 22 months) were observed between bortezomib-sensitive and -refractory patients. CarPan proved to be a safe and effective steroid-sparing regimen in a heavily pre-treated population of MM patients. (Trial registered at ClinicalTrial.gov: NCT01549431)

摘要翻译： 

蛋白酶体抑制剂(PIs)与组蛋白去乙酰化酶抑制剂(HDACis)在复发/难治性多发性骨髓瘤(RRMM)患者的治疗中已显示出协同作用。本项I期研究中,我们将第二代PI卡非佐米与HDACi帕比司他联用,旨在确定CarPan联合方案的最大耐受剂量(MTD),并评估其对RRMM患者的安全性与疗效。共入组32例患者(中位既往治疗线数为4)。确定MTD为卡非佐米36mg/m2(第1、2、8、9、15、16天给药)联合帕比司他20mg(每周三次,用药3周/停药1周,每28天为周期),持续治疗至疾病进展。在MTD剂量下,最常见的3/4级治疗相关不良事件为血小板减少症(41%)、疲劳(17%)和恶心/呕吐(12%)。客观缓解率和临床获益率分别为63%和68%。总体患者的中位无进展生存期和总生存期分别为8个月和23个月。在硼替佐米敏感与耐药患者之间,客观缓解率(55%对57%)、中位无进展生存期(8个月对7个月)和总生存期(24个月对22个月)均未观察到差异。研究证实,CarPan方案在经深度治疗的骨髓瘤患者群体中是一种安全有效的类节俭方案。(临床试验注册号:NCT01549431)

原文链接：

Combining carfilzomib and panobinostat to treat relapsed/refractory multiple myeloma: results of a Multiple Myeloma Research Consortium Phase I Study