Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Siltuximab in High-Risk Smoldering Multiple Myeloma
Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Siltuximab in High-Risk Smoldering Multiple Myeloma
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DOI：
10.1158/1078-0432.ccr-18-3470
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发表时间：
2019-07-01
影响因子：
11.5
通讯作者：
Goldschmidt, Hartmut
中科院分区：
文献类型：
--
作者：
Brighton, Timothy A.;Khot, Amit;Goldschmidt, Hartmut
目的：IL 6对骨髓瘤细胞的生长和存活具有重要作用。本研究评估了siltuximab阻断IL 6延迟从高风险闷烧多发性骨髓瘤（SMM）的过渡到multiple myeloma.Patients and Methods：在一项随机、双盲、安慰剂对照、多中心研究中，85例高风险SMM患者随机接受15 mg/kg siltuximab（43例）或安慰剂（42例）。主要终点是基于IMWG CRAB标准的1年无进展生存（PFS）率。次要终点包括进行性疾病指标率，PFS，和safety.Results：中位年龄为62岁（范围：21-84），57%是男性和87%的基线东部肿瘤协作组评分为0。1年PFS率为84.5%（西妥昔单抗）和74.4%（安慰剂）。中位随访29.2个月后，西妥昔单抗组32.6%的PFS事件发生，安慰剂组42.9%。西妥昔单抗未达到中位PFS，但安慰剂为23.5个月[HR 0.50（95%置信区间，0.24- 0.04）; P = 0.0597]。西妥昔单抗的安全性特征与安慰剂相当。西妥昔单抗组的大多数不良事件为2/3级;最常见的严重不良事件为感染/侵染和肾脏/泌尿系统疾病。两组死亡率均较低（siltuximab组3例死亡，安慰剂组4例死亡）。结论：虽然本研究不符合预先规定的方案假设标准，但数据表明siltuximab可能延缓高危SMM的进展。
Purpose: IL6 is important for the growth and survival of myeloma cells. This study evaluated blocking IL6 with siltuximab to delay the transition from high-risk smoldering multiple myeloma (SMM) to multiple myeloma.Patients and Methods: In a randomized, double-lind, placebo-controlled, multicenter study, 85 patients with high-risk SMM were randomized to 15 mg/kg siltuximab (43 patients) or placebo (42 patients). The primary endpoint was 1-year progression-free survival (PFS) rate, based on IMWG CRAB criteria. Secondary endpoints included progressive disease indicator rate, PFS, and safety.Results: Median age was 62 years (range: 21-84); 57% were male and 87% had a baseline Eastern Cooperative Oncology Group score of 0. The 1-year PFS rate was 84.5% (siltuximab) and 74.4% (placebo). After a median followup of 29.2 months, 32.6% of PFS events occurred with siltuximab and 42.9% with placebo. Median PFS was not reached with siltuximab but was 23.5 months with placebo [HR 0.50 (95% confidence interval, 0.24-.04); P = 0.0597]. The safety profile of siltuximab was comparable with placebo. Most adverse events in the siltuximab group were grade 2/3; the most common serious adverse events were infections/infestations, and renal/urinary disorders. Mortality was low in both groups (3 deaths in the siltuximab group and 4 in the placebo group).Conclusions: Although this study did not meet the prespecified protocol hypothesis criteria, data suggest that siltuximab may delay the progression of high-risk SMM.