MD Anderson Cancer Center, Houston, TX;
Blood. 2013 Oct 31;122(18):3122-8. doi: 10.1182/blood-2013-07-511170. Epub 2013 Sep 6.
We previously reported a phase 1b dose-escalation study of carfilzomib, lenalidomide, and low-dose dexamethasone (CRd) in relapsed or progressive multiple myeloma where the maximum planned dose (MPD) was carfilzomib 20 mg/m2 days 1 and 2 of cycle 1 and 27 mg/m2 days 8, 9, 15, 16, and thereafter; lenalidomide 25 mg days 1 to 21; and dexamethasone 40 mg once weekly on 28-day cycles. Herein, we present results from the phase 2 dose expansion at the MPD, focusing on the 52 patients enrolled in the MPD cohort. Median follow-up was 24.4 months. In the MPD cohort, overall response rate (ORR) was 76.9% with median time to response of 0.95 month (range, 0.5-4.6) and duration of response (DOR) of 22.1 months. Median progression-free survival was 15.4 months. ORR was 69.2% in bortezomib-refractory patients and 69.6% in lenalidomide-refractory patients with median DOR of 22.1 and 10.8 months, respectively. A median of 9.5 (range, 1-45) carfilzomib cycles were started with 7.7% of patients requiring carfilzomib dose reductions and 19.2% discontinuing CRd due to adverse events (AEs). Grade 3/4 AEs included lymphopenia (48.1%), neutropenia (32.7%), thrombocytopenia (19.2%), and anemia (19.2%). CRd at the MPD was well tolerated with robust, rapid, and durable responses.
我们之前报道了一项卡非佐米、来那度胺和低剂量地塞米松（CRd）在复发或进展性多发性骨髓瘤中的 1b 期剂量递增研究，其中最大计划剂量（MPD）为卡非佐米 20mg/m2，第 1 天和第 2 天周期 1，第 8 天、第 9 天、第 15 天和第 16 天以及此后 27mg/m2；来那度胺 25mg 第 1 天至第 21 天；地塞米松 40mg 每周一次，28 天为一个周期。在此，我们报告了 MPD 阶段 2 扩展的结果，重点介绍了 MPD 队列中招募的 52 名患者。中位随访时间为 24.4 个月。在 MPD 队列中，总缓解率（ORR）为 76.9%，中位缓解时间为 0.95 个月（范围为 0.5-4.6），缓解持续时间（DOR）为 22.1 个月。中位无进展生存期为 15.4 个月。在硼替佐米耐药的患者中，ORR 为 69.2%，在来那度胺耐药的患者中，ORR 为 69.6%，中位 DOR 分别为 22.1 和 10.8 个月。中位数为 9.5（范围为 1-45）个卡非佐米周期，7.7%的患者需要减少卡非佐米剂量，19.2%的患者因不良事件（AE）停止 CRd。3/4 级 AE 包括淋巴细胞减少（48.1%）、中性粒细胞减少（32.7%）、血小板减少（19.2%）和贫血（19.2%）。MPD 时的 CRd 耐受良好，具有强大、快速和持久的反应。
