文章：

艾沙妥昔单抗单药治疗难治性多发性骨髓瘤的I期试验

Phase I trial of isatuximab monotherapy in the treatment of refractory multiple myeloma

原文发布日期：2019-03-29

DOI: 10.1038/s41408-019-0198-4

类型: Article

开放获取: 是

英文摘要：

This phase I dose-escalation/expansion study evaluated isatuximab (anti-CD38 monoclonal antibody) monotherapy in patients with relapsed/refractory multiple myeloma (RRMM). Patients progressing on or after standard therapy received intravenous isatuximab (weekly [QW] or every 2 weeks [Q2W]). The primary objective was to determine the maximum tolerated dose (MTD) of isatuximab. Overall, 84 patients received ≥ 1 dose of isatuximab. The MTD was not reached; no cumulative adverse reactions were noted. The most frequent adverse events were infusion reactions (IRs), occurring in 37/73 patients (51%) following introduction of mandatory prophylaxis. IRs were mostly grade 1/2, occurred predominantly during Cycle 1, and led to treatment discontinuation in two patients. CD38 receptor occupancy reached a plateau of 80% with isatuximab 20 mg/kg (highest dose tested) and was associated with clinical response. In patients receiving isatuximab ≥ 10 mg/kg, overall response rate (ORR) was 23.8% (15/63), including one complete response. In high-risk patients treated with isatuximab 10 mg/kg (QW or Q2W), ORR was 16.7% (3/18). Median (range) duration of response at doses ≥ 10 mg/kg was 25 (8–30) weeks among high-risk patients versus 36 (6–85) weeks for other patients. In conclusion, isatuximab demonstrated a manageable safety profile and clinical activity in patients with RRMM.
 

摘要翻译： 

这项I期剂量递增/扩展研究评估了伊沙妥昔单抗（抗CD38单克隆抗体）单药治疗复发/难治性多发性骨髓瘤患者的效果。经标准治疗无效或治疗后病情进展的患者接受静脉注射伊沙妥昔单抗（每周一次或每两周一次）。主要研究目的是确定伊沙妥昔单抗的最大耐受剂量。共计84例患者接受≥1剂伊沙妥昔单抗治疗。未达到最大耐受剂量；未观察到累积性不良反应。最常见的不良事件是输注反应，在引入强制性预防措施后，73例患者中有37例（51%）出现该反应。输注反应多为1/2级，主要发生在治疗周期1期间，并导致2例患者中止治疗。CD38受体占有率在伊沙妥昔单抗20mg/kg（测试最高剂量）时达到80%的平台期，且与临床应答相关。在接受伊沙妥昔单抗≥10mg/kg的患者中，总体缓解率为23.8%（15/63），其中包含1例完全缓解。接受伊沙妥昔单抗10mg/kg治疗的高危患者中，总体缓解率为16.7%（3/18）。在剂量≥10mg/kg组中，高危患者的中位缓解持续时间（范围）为25周，其他患者为36周。综上所述，伊沙妥昔单抗在复发/难治性多发性骨髓瘤患者中展现出可控的安全性和临床活性。

原文链接：

Phase I trial of isatuximab monotherapy in the treatment of refractory multiple myeloma