Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
Division of Hematology, Mayo Clinic Rochester, Rochester, Minnesota, USA.
Am J Hematol. 2023 Aug;98(8):1277-1285. doi: 10.1002/ajh.26990. Epub 2023 Jun 19.
In this phase 1/2 study, carfilzomib was added to high-dose melphalan conditioning prior to autologous stem cell transplantation (ASCT) in patients with multiple myeloma that had been treated with ≤2 prior lines of therapy. Carfilzomib was escalated at doses of 27, 36, 45, and 56 mg/m2 on days -6, -5, -2, and -1 before ASCT in the phase 1 component of the study. In addition, all the patients received melphalan 100 mg/m on days -4 and -3. The primary endpoint of the phase 1 component was to identify the maximum tolerated dose, and the primary endpoint of the phase 2 component was the rates of complete response (≥CR) at 1 year after ASCT. The phase 1 dose escalation cohort included 14 patients, and 35 patients were included in the phase 2 cohort. The maximum tested dose was 56 mg/m (MTD). The median time from diagnosis to study enrollment was 5.8 (range 3.4-88.4) months, and 16% of patients had obtained a ≥CR prior to ASCT. The best response within 1 year after ASCT was a ≥ CR rate in 22% for the entire cohort, and 22% for patients treated at the MTD. The ≥VGPR rates improved from 41% before ASCT to 77% by 1 year after ASCT. One patient had a grade 3 renal adverse event, and renal function returned to baseline with supportive care. The rate of grade 3-4 cardiovascular toxicity was 16%. The addition of carfilzomib to melphalan conditioning was safe and resulted in deep responses after ASCT.
在这项 1/2 期研究中，在接受 ≤2 线治疗的多发性骨髓瘤患者中，在高剂量马法兰预处理后添加卡非佐米进行自体干细胞移植 (ASCT)。在研究的 1 期部分，卡非佐米在 ASCT 前的第-6、-5、-2 和-1 天分别以 27、36、45 和 56mg/m2 的剂量递增。此外，所有患者均在第-4 和-3 天接受 100mg/m2 的马法兰。1 期部分的主要终点是确定最大耐受剂量，2 期部分的主要终点是 ASCT 后 1 年完全缓解（≥CR）的发生率。1 期剂量递增队列包括 14 例患者，2 期队列包括 35 例患者。测试的最大剂量为 56mg/m（MTD）。从诊断到研究入组的中位时间为 5.8 个月（范围 3.4-88.4），16%的患者在 ASCT 前已获得≥CR。整个队列的最佳反应是 ASCT 后 1 年内≥CR 率为 22%，MTD 治疗患者为 22%。ASCT 前的≥VGPR 率为 41%，ASCT 后 1 年提高至 77%。1 例患者出现 3 级肾不良事件，经支持治疗后肾功能恢复基线。3-4 级心血管毒性的发生率为 16%。卡非佐米联合马法兰预处理安全，并在 ASCT 后产生深度反应。
