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.

中文翻译：

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艾沙妥昔单抗单药治疗难治性多发性骨髓瘤的一期临床试验。

这项I期剂量递增/扩展研究评估了复发/难治性多发性骨髓瘤（RRMM）患者的isatuximab（抗CD38单克隆抗体）单药治疗。在标准治疗中或治疗后进展的患者接受静脉注射艾妥昔单抗（每周[QW]或每2周[Q2W]）。主要目的是确定艾沙妥昔单抗的最大耐受剂量（MTD）。总体而言，有84例患者接受了≥1剂量的伊妥昔单抗治疗。未达到MTD；没有发现累积的不良反应。引入强制性预防措施后，最常见的不良事件是输注反应（IR），在37/73例患者中发生（51％）。IR大多为1/2级，主要发生在第1周期，导致两名患者中止治疗。异烟单抗20 mg / kg（测试的最高剂量）的CD38受体占有率达到80％的平稳期，并与临床反应相关。接受伊妥昔单抗≥10 mg / kg的患者，总缓解率（ORR）为23.8％（15/63），包括一项完全缓解。在接受10 mg / kg isatuximab（QW或Q2W）治疗的高危患者中，ORR为16.7％（3/18）。在高危患者中，≥10 mg / kg剂量的反应中位（持续时间）为25（8-30）周，而其他患者为36（6-85）周。总之，伊沙妥昔单抗在RRMM患者中显示出可控的安全性和临床活动。ORR为16.7％（3/18）。在高危患者中，≥10 mg / kg剂量的反应中位（持续时间）为25（8-30）周，而其他患者为36（6-85）周。总之，伊沙妥昔单抗在RRMM患者中显示出可控的安全性和临床活动。ORR为16.7％（3/18）。在高危患者中，≥10 mg / kg剂量的反应中位（持续时间）为25（8-30）周，而其他患者为36（6-85）周。总之，伊沙妥昔单抗在RRMM患者中显示出可控的安全性和临床活动。