塞利尼索联合化疗方案在复发/难治性多发性骨髓瘤治疗中的探索——来自多中心、开放标签的LAUNCH研究中期数据结果  

Selinexor combined with chemotherapy in relapsed/refractory multiple myeloma:interim results from the multi-center,open-label LAUNCH study

作　　者：孙春艳[1] 房佰俊 高广勋 周芙玲[4] 何爱丽[5] 赵菲 李俊颖 张纯[1] 黎纬明[1] 程辉[6] 蔡惠丽 陈斌[8] 郭静明[7] 胡豫[1] SUN Chunyan;FANG Baijun;GAO Guangaun;ZHOU Fuling;HE Aili;ZHAO Fei;LI Junying;ZHANG Chun;LI Weiming;CHENG Hui;CAI Huili;CHEN Bin;GUO Jingming;HU Yu(Department of Hematology,Union Hospital,Tongji Medical Collage,Huazhong University of Science and Technology,Wuhan,430022,China;Department of Hematology,the Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer Hospital;Department of Hematology,Xijing Hospital;Department of Hematology,Zhongnan Hospital of Wuhan University;Department of Hematology,the Second Affiliated Hospital of Xian Jiaotong University;Department of Hematology,Wuhan No.1 Hospital;Department of Hematology,Center People's Hospital of Yichang;Department of Hematology,Hubei Provincial Hospital of Traditional Chinese Medicine)

机构地区：[1]华中科技大学同济医学院附属协和医院血液科,武汉430022 [2]郑州大学附属肿瘤医院(河南省肿瘤医院)血液科 [3]空军军医大学西京医院血液科 [4]武汉大学中南医院血液科 [5]西安交通大学第二附属医院血液科 [6]武汉市第一医院血液科 [7]宜昌市中心人民医院血液科 [8]湖北省中医院血液科

出　　处：《临床血液学杂志》2023年第7期468-472,共5页Journal of Clinical Hematology

基　　金：国家自然科学基金项目(No:81974007,82270214)。

摘　　要：目的:评估塞利尼索、地塞米松(Sd)联合化疗药物在复发/难治性多发性骨髓瘤患者中的疗效及安全性。方法:这是一项多中心、开放标签、单臂的临床研究,分为2个治疗臂:SDd组:塞利尼索80 mg d1,8,15,22,地塞米松40 mg d1,8,15,22,脂质体阿霉素25~35 mg/m2,d1;SCd组:塞利尼索100 mg d1,8,15,22,地塞米松40 mg d1,8,15,22,环磷酰胺300 mg/m2,d1,8,15,22。每28 d为1个疗程,共12个疗程。主要终点为客观缓解率(ORR),次要终点包括安全性、无进展生存期、总生存期等。结果:截止到2023年4月30日,共入组36例患者。中位年龄为59(29~74)岁,患者应用塞利尼索的时间距离初次诊断的中位时间为3.5(0.5~15.5)年,中位既往治疗线数为3(1~8)。其中6例(16.7%)患者伴髓外病灶,12例(33.3%)患者伴高危细胞遗传学,4例(11.1%)患者既往接受过自体造血干细胞移植,3例(8.3%)患者既往接受过CAR-T治疗。既往药物暴露情况:硼替佐米(94.4%)、来那度胺(80.6%)、泊马度胺(41.7%)、达雷妥尤单抗(27.8%),阿霉素和环磷酰胺(19.4%)。1例患者已完成12个疗程治疗,4例患者治疗>10个疗程,12例患者仍在治疗中,最主要的出组原因依次为患者要求退出、疾病进展和治疗不耐受。在可评估的29例患者中,ORR为48.3%(14/29),包括完全缓解1例,非常好的部分缓解1例,部分缓解12例。治疗至缓解中位时间为2个月。中位无进展生存期为11.6个月,总生存期未达到,1年生存率为75.0%。其中SDd组(n=19)的ORR为52.6%;SCd组(n=10)的ORR为40.0%。治疗相关不良反应的发生主要集中在前2个治疗周期,多数为1~2级,通过积极的支持治疗或对症处理后,不良反应均有所改善。其中最常见的血液学不良反应(整体/3~4级)为:血小板减少(58.3%/25.0%),白细胞减少(50.0%/30.6%)和贫血(41.7%/22.2%);最常见的非血液学不良反应(整体/3~4级)为:恶心(52.8%/2.8%)、呕吐(38.9%/5.6%)和乏力(30.6%/2.8%)。结论:以Sd为基础联合脂质体阿Objective:To evaluate the preliminary efficacy and safety of combination of selinexor and dexamethasone(Sd)with chemotherapy in patients with relapsed/refractory multiple myeloma.Methods:This is a multicenter,open label,single arm clinical study divided into two treatment arms:SDd arm:selinexor 80 mg d1,8,15,22,dexamethasone 40 mg d1,8,15,22,and liposome doxorubicin 25-35 mg/m~2 d1;SCd arm:selinexor 100 mg d1,8,15,22,dexamethasone 40 mg d1,8,15,22,and cyclophosphamide 300 mg/m~2 d1,8,15,22.28 d per cycle in both arms,and a total of 12 cycles.The primary endpoint is the objective response rate(ORR),while secondary endpoints include safety,progression free survival(PFS),and overall survival(OS).Results:As of April 30,2023,a total of 36 patients were enrolled.The median age was 59(range 29-74)years old,and the median time between the initial diagnosis and enrollment was 3.5(range 0.5-15.5)years.Median number of previous treatment lines of 3(range 1-8).Six patients(16.7%)had extramedullary disease,12 patients(33.3%)had high-risk cytogenetic abnormalities,4 patients(11.1%)had previously received autologous stem cell transplantation,and 3 patients(8.3%)had previously treated with CAR-T.Previous drug exposure:bortezomib(94.4%),lenalidomide(80.6%),pomadolide(41.7%),daratumumab(27.8%),doxorubicin and cyclophosphamide(19.4%).1 patient had completed 12 cycles of treatment,4 patients had received more than 10 cycles of treatment,and 12 patients were still under treatment.Median follow-up time:2.25(0.25-12.00)months.Among the 29 evaluable patients,the objective response rate(ORR)was 48.3%(14/29),including 1 case with complete response,1 case with very good partial response,12 cases with partial response.The disease control rate was 89.7%(26/29).Median time from treatment to first response was 2 months.The median PFS was 11.6 months,the median OS was not reached,and 1-year OS rate was 75.0%.The ORR was 52.6%in SDd arm(n=19)and 40.0%in SCd arm(n=10).The treatment related adverse events was mainly concentrated in the first two t

关 键 词：复发/难治多发性骨髓瘤 塞利尼索 化疗 

分 类 号：R733.3[医药卫生—肿瘤]