首页> 美国卫生研究院文献>Blood Cancer Journal >Combining carfilzomib and panobinostat to treat relapsed/refractory multiple myeloma: results of a Multiple Myeloma Research Consortium Phase I Study
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Combining carfilzomib and panobinostat to treat relapsed/refractory multiple myeloma: results of a Multiple Myeloma Research Consortium Phase I Study

机译:卡非佐米和panobinostat联合治疗复发/难治性多发性骨髓瘤:多发性骨髓瘤研究联盟第一阶段研究的结果

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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: )
机译:蛋白酶体(PIs)和组蛋白去乙酰化酶抑制剂(HDACis)先前已显示在复发/难治性多发性骨髓瘤(RRMM)患者的治疗中具有协同活性。在这项1期研究中,我们将第二代PI卡非佐米与HDACi panobinostat组合使用,以确定该组合(CarPan)的最大耐受剂量(MTD),并评估RRMM患者的安全性和有效性。招募了32例患者(在先治疗4线的中位数)。 MTD为卡非佐米36?mg / m 2 (在第1、2、8、9、15和16天)和panobinostat 20?mg(TIW,3周/ 1周,每28天) ),直至进展。在MTD,最常见的3/4级与治疗相关的不良事件是血小板减少症(41%),疲劳(17%)和恶心/呕吐(12%)。客观缓解率(ORR)和临床获益率分别为63%和68%。整个人群的中位无进展生存期(PFS)和总体生存期(OS)分别为8个月和23个月。在对硼替佐米敏感和难治性患者中,ORR(55%vs. 57%),中位PFS(第8个月对7个月)和OS(24个月对22个月)方面无差异。 CarPan被证明是经过大量预处理的MM患者的一种安全有效的类固醇激素疗法。 (已在ClinicalTrial.gov上注册的试用版:)

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