Myeloma Division, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, New Jersey.
Department of Medicine, Sarah Cannon Research Institute, Nashville, Tennessee.
Am J Hematol. 2019 Jul;94(7):794-802. doi: 10.1002/ajh.25498. Epub 2019 May 13.
Twice-weekly carfilzomib (27 mg/m ) with lenalidomide-dexamethasone (KRd) is a standard-of-care in relapsed or refractory multiple myeloma (RRMM). This phase 1b study evaluated KRd with once-weekly carfilzomib in RRMM. Patients received carfilzomib (30-minute infusion; 56 or 70mg/m ) on days 1, 8, and 15; lenalidomide 25 mg on days 1-21; and dexamethasone 40 mg on days 1, 8, 15, and 22 (day 22 omitted for cycles 9+) of 28-day cycles. Primary objective was safety/tolerability; efficacy was a secondary objective. Fifty-six RRMM patients enrolled: 22 during dose evaluation (56-mg/m , n = 10; 70-mg/m , n = 12) and 34 during dose expansion (all initiated dosing at 70 mg/m ). After 2 fatal adverse events (AEs) during 70-mg/m dose expansion, dosage reduction to 56 mg/m was permitted. Results are presented for carfilzomib 56-mg/m (n = 10) and 70-mg/m groups (dose evaluation/expansion; n = 46). Median carfilzomib dose was 53.2 mg/m (56-mg/m group) and 62.4 mg/m (70-mg/m group). Grade ≥3 AE rates were 70.0% (56 mg/m ) and 69.6% (70 mg/m ). Overall response rates were 90.0% (56 mg/m ) and 89.1% (70 mg/m ); ≥very good partial response rates were 50.0% (56 mg/m ) and 73.9% (70 mg/m ). Once-weekly KRd was active with acceptable toxicity in RRMM, supporting further evaluation of this regimen.
卡非佐米（27mg/m）每周两次联合来那度胺-地塞米松（KRd）是复发性或难治性多发性骨髓瘤（RRMM）的标准治疗方法。这项 1b 期研究评估了 RRMM 中每周一次卡非佐米联合 KRd 的疗效。患者接受卡非佐米（30 分钟输注；56 或 70mg/m），第 1、8 和 15 天；来那度胺 25mg，第 1-21 天；地塞米松 40mg，第 1、8、15 和 22 天（第 22 天在第 9 个周期及以后省略），每 28 天为一个周期。主要目的是评估安全性/耐受性；疗效是次要目的。56 例 RRMM 患者入组：剂量评估期间（56mg/m，n=10；70mg/m，n=12）入组 22 例，剂量扩展期间（均起始剂量为 70mg/m）入组 34 例。在 70mg/m 剂量扩展期间发生 2 例致死性不良事件（AE）后，允许剂量减少至 56mg/m。本文报告了卡非佐米 56mg/m（n=10）和 70mg/m 组（剂量评估/扩展；n=46）的结果。卡非佐米的中位剂量为 53.2mg/m（56mg/m 组）和 62.4mg/m（70mg/m 组）。≥3 级 AE 发生率为 70.0%（56mg/m）和 69.6%（70mg/m）。总缓解率分别为 90.0%（56mg/m）和 89.1%（70mg/m）；≥非常好的部分缓解率分别为 50.0%（56mg/m）和 73.9%（70mg/m）。每周一次 KRd 在 RRMM 中具有活性且毒性可接受，支持进一步评估该方案。
