泊马度胺
来那度胺
中性粒细胞减少症
医学
内科学
不利影响
地塞米松
多发性骨髓瘤
沙利度胺
硼替佐米
养生
临床研究阶段
胃肠病学
耐火材料(行星科学)
肿瘤科
Carfilzomib公司
达拉图穆马
外科
伊扎莫布
毒性
物理
天体生物学
作者
Joseph Mikhael,Paul G. Richardson,Saad Z. Usmani,Noopur Raje,William I. Bensinger,Chatchada Karanes,Frank Campana,Dheepak Kanagavel,Franck Dubin,Qianying Liu,Dorothée Semiond,Kenneth C. Anderson
出处
期刊:Blood
[American Society of Hematology]
日期:2019-07-11
卷期号:134 (2): 123-133
被引量:63
标识
DOI:10.1182/blood-2019-02-895193
摘要
Abstract This phase 1b dose-escalation study evaluated isatuximab plus pomalidomide/dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM). Patients who had received ≥2 prior MM therapies, including lenalidomide and a proteasome inhibitor (PI), were enrolled and received isatuximab at 5, 10, or 20 mg/kg (weekly for 4 weeks, followed by every 2 weeks), pomalidomide 4 mg (days 1-21), and dexamethasone 40 mg (weekly) in 28-day cycles until progression/intolerable toxicity. The primary objective was to determine the safety and recommended dose of isatuximab with this combination. Secondary objectives included evaluation of pharmacokinetics, immunogenicity, and efficacy. Forty-five patients received isatuximab (5 [n = 8], 10 [n = 31], or 20 [n = 6] mg/kg). Patients received a median of 3 (range, 1-10) prior lines; most were refractory to their last regimen (91%), with 82% lenalidomide-refractory and 84% PI-refractory. Median treatment duration was 9.6 months; 19 patients (42%) remain on treatment. Most common adverse events included fatigue (62%), and upper respiratory tract infection (42%), infusion reactions (42%), and dyspnea (40%). The most common grade ≥3 treatment-emergent adverse event was pneumonia, which occurred in 8 patients (17.8%). Hematologic laboratory abnormalities were common (lymphopenia, leukopenia, anemia, 98% each; neutropenia, 93%; and thrombocytopenia, 84%). Overall response rate was 62%; median duration of response was 18.7 months; median progression-free survival was 17.6 months. These results demonstrate potential meaningful clinical activity and a manageable safety profile of isatuximab plus pomalidomide/dexamethasone in heavily pretreated patients with RRMM. The 10 mg/kg weekly/every 2 weeks isatuximab dose was selected for future studies. This trial was registered at www.clinicaltrials.gov as #NCT02283775.
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