Hematology Department, University Hospital Hôtel-Dieu, Nantes, France;
Hematology Department, University Hospital, Reims, France;
Blood. 2015 May 14;125(20):3100-4. doi: 10.1182/blood-2015-02-626168. Epub 2015 Mar 17.
This phase 1/2 dose-escalation study investigated the combination of carfilzomib with melphalan and prednisone (CMP) in patients aged >65 years with newly diagnosed multiple myeloma (MM). Melphalan and prednisone were administered orally on days 1 to 4; carfilzomib was IV administered on days 1, 2, 8, 9, 22, 23, 29, and 30 of a 42-day cycle. Patients received up to 9 cycles of CMP. In the phase 1 dose-escalation portion, the primary objectives were to determine the incidence of dose-limiting toxicities during the first cycle of CMP treatment to define the maximal tolerated dose (MTD) of carfilzomib. In the phase 2 portion, the primary objective was to evaluate the overall response rate (ORR) of CMP. In the phase 1 portion of the study, 24 patients received CMP at carfilzomib dosing levels of 20 mg/m(2), 27 mg/m(2), 36 mg/m(2), and 45 mg/m(2). The MTD was established as 36 mg/m(2). In the phase 2 portion of the study, 44 patients were enrolled at the MTD. Among 50 efficacy-evaluable patients treated at the MTD, the ORR was 90%. The projected 3-year overall survival rate was 80%. The combination of CMP was observed to be effective in elderly patients with newly diagnosed MM. This trial was registered at www.clinicaltrials.gov as #NCT01279694 (Eudract identifier 2010-019462-92).
这项 1/2 期剂量递增研究调查了卡非佐米联合马法兰和泼尼松（CMP）在新诊断多发性骨髓瘤（MM）的>65 岁患者中的疗效。马法兰和泼尼松在第 1 至 4 天口服给予；卡非佐米在第 1、2、8、9、22、23、29 和 30 天的 42 天周期中静脉给予。患者接受最多 9 个周期的 CMP。在 1 期剂量递增部分，主要目标是确定 CMP 治疗第一周期的剂量限制毒性发生率，以确定卡非佐米的最大耐受剂量（MTD）。在 2 期部分，主要目标是评估 CMP 的总缓解率（ORR）。在研究的 1 期部分，24 名患者接受了卡非佐米剂量为 20 mg/m(2)、27 mg/m(2)、36 mg/m(2)和 45 mg/m(2)的 CMP。MTD 确定为 36 mg/m(2)。在研究的 2 期部分，44 名患者在 MTD 下入组。在 50 名可评估疗效的 MTD 治疗患者中，ORR 为 90%。预计 3 年总生存率为 80%。在新诊断的 MM 老年患者中，CMP 联合方案观察到有效。这项试验在 www.clinicaltrials.gov 上注册为 #NCT01279694（Eudract 标识符 2010-019462-92）。
