文章：

抗体-药物偶联物GSK2857916治疗复发/难治性多发性骨髓瘤：I期剂量扩展研究安全性与疗效更新

Antibody–drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy from dose expansion phase I study

原文发布日期：2019-03-20

DOI: 10.1038/s41408-019-0196-6

类型: Article

开放获取: 是

英文摘要：

Interim analyses of a phase I study with GSK2857916, an antibody–drug conjugate against B cell maturation antigen, have previously reported a 60% overall response and 7.9 months progression-free survival in relapsed/refractory multiple myeloma (MM). We provide updated safety and efficacy results of the BMA117159 trial following an additional 14 months' follow-up. This open-label, first-in-human, phase I study was conducted at nine centres in the USA, Canada and the UK, and included adults with MM and progressive disease after stem cell transplantation, alkylators, proteasome inhibitors, and immunomodulators. In part 1, the recommended dose of 3.4 mg/kg was identified; in part 2, patients received GSK2857916 3.4 mg/kg once every 3 weeks. Selected part 2 safety/tolerability and efficacy endpoints are reported. Twenty-one (60.0%; 95% confidence interval (CI) 42.1–76.1) of 35 patients achieved partial response or better, including two stringent complete responses and three complete responses. The median progression-free survival was 12 months and median duration of response was 14.3 months. Thrombocytopenia and corneal events were commonly reported; no new safety signals were identified. GSK2857916 was well tolerated and demonstrated a rapid, deep and durable response in heavily pre-treated patients with relapsed/refractory MM, consolidating the interim analyses conclusions that GSK2857916 is a promising treatment for these patients.
 

摘要翻译： 

针对B细胞成熟抗原的抗体药物偶联物GSK2857916的I期研究中期分析此前曾报告，在复发/难治性多发性骨髓瘤患者中达到60%的总缓解率和7.9个月的无进展生存期。本文提供BMA117159试验经过额外14个月随访后的最新安全性和有效性结果。这项开放标签、首次人体I期研究在美国、加拿大和英国的9个中心进行，纳入经干细胞移植、烷化剂、蛋白酶体抑制剂和免疫调节剂治疗后仍出现疾病进展的成年多发性骨髓瘤患者。在研究第一部分确定了3.4 mg/kg的推荐剂量；在第二部分中，患者每三周接受一次3.4 mg/kg的GSK2857916治疗。本文报告了第二部分选定的安全性/耐受性和有效性终点。35例患者中21例（60.0%；95%置信区间42.1-76.1）达到部分缓解或更好疗效，包括2例严格完全缓解和3例完全缓解。中位无进展生存期为12个月，中位缓解持续时间为14.3个月。血小板减少症和角膜事件常见；未发现新的安全性信号。GSK2857916耐受性良好，并在经过深度治疗的复发/难治性多发性骨髓瘤患者中展现出快速、深度且持久的疗效，巩固了中期分析结论：GSK2857916是治疗这类患者的前景可期的方案。

原文链接：

Antibody–drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy from dose expansion phase I study