Princess Margaret Cancer Centre, Toronto, ON, Canada.
Department of Medicine, Myeloma Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Blood Cancer J. 2019 Mar 20;9(4):37. doi: 10.1038/s41408-019-0196-6.
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.
GSK2857916 是一种针对 B 细胞成熟抗原的抗体药物偶联物，此前开展的 I 期研究的中期分析结果显示，复发/难治性多发性骨髓瘤（MM）患者的总缓解率为 60%，无进展生存期为 7.9 个月。我们提供了 BMA117159 试验在额外 14 个月随访后的最新安全性和疗效结果。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，纳入了干细胞移植后疾病进展、接受烷化剂、蛋白酶体抑制剂和免疫调节剂治疗的 MM 成年患者。在第 1 部分中，确定了 3.4mg/kg 的推荐剂量；在第 2 部分中，患者接受 GSK2857916 3.4mg/kg，每 3 周 1 次。报告了部分 2 的安全性/耐受性和疗效终点。35 例患者中有 21 例（60.0%；95%置信区间（CI）42.1-76.1）达到部分缓解或更好，包括 2 例严格完全缓解和 3 例完全缓解。无进展生存期的中位数为 12 个月，缓解持续时间的中位数为 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，在复发/难治性 MM 患者中表现出快速、深度和持久的缓解，巩固了中期分析的结论，即 GSK2857916 是这些患者有前景的治疗选择。
