Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma
Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma
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DOI：
10.1182/blood-2016-03-705210
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发表时间：
2016-07-07
期刊：
影响因子：
20.3
通讯作者：
Nahi, Hareth
中科院分区：
文献类型：
--
作者：
Usmani, Saad Z.;Weiss, Brendan M.;Nahi, Hareth
既往报告了达雷妥尤单抗单药治疗多发性骨髓瘤（MM）的疗效和有利的安全性特征。在此，我们对148例接受达雷妥尤单抗16 mg/kg治疗的患者进行了更新的汇总分析。数据来自首次人体I/II期研究的第2部分，研究对象为既往≥ 2种治疗后复发或难治的患者，以及既往接受过≥ 3种治疗（包括蛋白酶体抑制剂[PI]和免疫调节药物[IMiD]）或双重难治的患者的II期研究。在汇总人群中，患者接受了中位5线既往治疗（范围：2 - 14线既往治疗），86.5%的患者对PI和IMiD双重难治。总有效率为31.1%，其中13例部分缓解，4例完全缓解，3例严格完全缓解。中位缓解持续时间为7.6个月（95%置信区间[CI]，5.6至不可评价[NE]）。中位无进展生存期（PFS）和总生存期（OS）分别为4.0个月（95% CI，2.8-5.6个月）和20.1个月（95% CI，16.6个月至NE）。当按缓解者vs疾病稳定/最小缓解vs疾病进展/NE分层时，中位PFS为15.0个月（95% CI，7.4个月至NE）vs 3.0个月（95% CI，2.8- 3.7个月）vs 0.9个月（95% CI，0.9-1.0个月），中位OS分别为NE（95% CI，NE至NE）vs 18.5个月（95% CI，15.1-22.4个月）vs 3.7个月（95% CI，1.7-7.6个月）。未发现新的安全性信号。在该汇总数据集中，达雷妥尤单抗16 mg/kg单药治疗显示出快速、深度和持久的缓解，临床获益扩展至疾病稳定或更好的患者。
The efficacy and favorable safety profile of daratumumab monotherapy in multiple myeloma (MM) was previously reported. Here, we present an updated pooled analysis of 148 patients treated with daratumumab 16 mg/kg. Data were combined from part 2 of a first-in-human phase 1/2 study of patients who relapsed after or were refractory to >= 2 prior therapies and a phase 2 study of patients previously treated with >= 3 prior lines of therapy (including a proteasome inhibitor [PI] and an immunomodulatory drug [IMiD]) or were double refractory. Among the pooled population, patients received a median of 5 prior lines of therapy (range, 2 to 14 prior lines of therapy), and 86.5% were double refractory to a PI and an IMiD. Overall response rate was 31.1%, including 13 very good partial responses, 4 complete responses, and 3 stringent complete responses. The median duration of response was 7.6 months (95% confidence interval [CI], 5.6 to not evaluable [NE]). The median progression-free survival (PFS) and overall survival (OS) were 4.0 months (95% CI, 2.8-5.6 months) and 20.1 months (95% CI, 16.6 months to NE), respectively. When stratified by responders vs stable disease/minimal response vs progressive disease/NE, median PFS was 15.0 months (95% CI, 7.4 months to NE) vs 3.0 months(95% CI, 2.8-3.7months) vs 0.9 months (95% CI, 0.9-1.0 months), respectively, and median OS was NE(95% CI, NE to NE) vs 18.5 months (95% CI, 15.1-22.4 months) vs 3.7 months (95% CI, 1.7-7.6 months), respectively. No new safety signals were identified. In this pooled data set, daratumumab 16 mg/kg monotherapy demonstrated rapid, deep, and durable responses, with a clinical benefit that extended to patients with stable disease or better.