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Filanesib plus bortezomib and dexamethasone in relapsed/refractory t(11;14) and 1q21 gain multiple myeloma
Cancer Medicine ( IF 2.9 ) Pub Date : 2021-12-17 , DOI: 10.1002/cam4.4451
Darren Pan 1 , Jonathan L Kaufman 2 , Myo Htut 3 , Manish Agrawal 4 , Amitabha Mazumder 5 , Robert F Cornell 6 , Jeffrey A Zonder 7 , Joseph W Fay 8 , Manuel R Modiano 9 , Erin L Moshier 10 , Selena A Rush 11 , Brian J Tunquist 11 , Ajai Chari 1
Affiliation  

Filanesib is a first-in-class kinesin spindle protein inhibitor which demonstrated safety and encouraging activity in combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma in a preliminary analysis of dose-escalation phase results. This multicenter study included first a dose-escalation phase to determine maximum tolerated dose of two schedules of filanesib, bortezomib, and dexamethasone and a subsequent dose-expansion phase using the maximum tolerated doses. In the dose-expansion phase, 28 patients were evaluable for safety and efficacy. The most common grade ≥3 adverse events were neutropenia (21%) and anemia (18%), which were noncumulative and reversible, and hypertension (18%). The overall response rate was 43% with median duration of response not yet reached (range, 2.8–23.7+ months) with median follow-up of 6.3 months. A post hoc analysis incorporated 29 dose-escalation phase patients who received therapeutic filanesib doses, with an overall response rate of 39% and median duration of response of 18.0 months among the 57 total patients with median progression-free survival of 8.5 months. Notably, the PFS of high risk patients was comparable at 8.5 months, driven by the patients with 1q21 gain, characterized by increased MCL-1 expression, with a PFS of 9.1 months versus 3.5 months for the remainder of high risk patients. Patients with t(11;14) also had an encouraging PFS of 15.0 months. The combination of filanesib, bortezomib, and dexamethasone continues to show safety and encouraging activity in relapsed/refractory multiple myeloma, particularly in those patients with 1q21 gain and t(11;14).

中文翻译:

Filanesib 加硼替佐米和地塞米松治疗复发/难治性 t(11;14) 和 1q21 多发性骨髓瘤

Filanesib 是一种一流的驱动蛋白纺锤体蛋白抑制剂,在剂量递增阶段结果的初步分析中,与硼替佐米和地塞米松联合治疗复发/难治性多发性骨髓瘤显示出安全性和令人鼓舞的活性。这项多中心研究首先包括一个剂量递增阶段,以确定 filanesib、bortezomib 和 dexamethasone 两个方案的最大耐受剂量,以及随后使用最大耐受剂量的剂量扩展阶段。在剂量扩展阶段,28 名患者的安全性和有效性进行了评估。最常见的≥3级不良事件是中性粒细胞减少症(21%)和贫血(18%),它们是非累积性和可逆性的,以及高血压(18%)。总体缓解率为 43%,中位缓解持续时间尚未达到(范围为 2.8-23.7+ 个月),中位随访时间为 6.3 个月。事后分析纳入了 29 名接受治疗性 filanesib 剂量的剂量递增阶段患者,总体缓解率为 39%,57 名患者的中位缓解持续时间为 18.0 个月,中位无进展生存期为 8.5 个月。值得注意的是,高风险患者的 PFS 为 8.5 个月,这是由 1q21 增益的患者驱动的,其特征是 MCL-1 表达增加,PFS 为 9.1 个月,而其余高风险患者的 PFS 为 3.5 个月。t(11;14) 患者的 PFS 也令人鼓舞,为 15.0 个月。filanesib、bortezomib 和 dexamethasone 的组合在复发/难治性多发性骨髓瘤中继续显示出安全性和令人鼓舞的活性,特别是对于那些 1q21 增益和 t(11;14) 的患者。
更新日期:2022-01-05
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