伊沙佐米、来那度胺、地塞米松治疗复发/难治多发性骨髓瘤的疗效与安全性分析:一项国内多中心真实世界研究  

The efficacy and safety profile of ixazomib/lenalidomide/dexamethasone in relapsed/refractory multiple myeloma:a multicenter real-world study in China

作　　者：杨扬 夏忠军[2] 张文皓[3] 傅琤琤[4] 鲍立[5] 陈兵 丁凯阳[7] 王思力[8] 罗军[9] 李炳宗[10] 化罗明[11] 杨威[12] 周新[13] 王亮[14] 徐天虹 王维达 吴国林[7] 黄耘[8] 李晶 刘澎 Yang Yang;Xia Zhongjun;Zhang Wenhao;Fu Chengcheng;Bao Li;Chen Bing;Ding Kaiyang;Wang Sili;Luo Jun;Li Bingzong;Hua Luoming;Yang Wei;Zhou Xin;Wang Liang;Xu Tianhong;Wang Weida;Wu Guolin;Huang Yun;Li Jing;Liu Peng(Department of Hematology,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Department of Hematologic Oncology,Sun Yat-sen University Cancer Center,Guangzhou 510060,China;Department of Hematology,Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine,Shanghai 200092,China;Department of Hematology,The First Affiliated Hospital of Soochow University,Jiangsu Institute of Hematology,Suzhou 210056,China;Department of Hematology,Beijing Jishuitan Hospital,Beijing 100035,China;Department of Hematology,The Affiliated Nanjing Drum Tower Hospital,Nanjing University Medical School,Nanjing 210008,China;Department of Hematology,Anhui Provincial Cancer Hospital,Hefei 230031,China;Department of Hematology,The First Affiliated Hospital of Xiamen University,Xiamen 361003,China;Department of Hematology,The First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China;Department of Hematology,The Second Affiliated Hospital of Soochow University,Suzhou 215004,China;Department of Hematology,The Affiliated Hospital of Hebei University,Baoding 071030,China;Department of Hematology,Shengjing Hospital of China Medical University,Shenyang 110004,China;Department of Hematology,Wuxi People Hospital,Wuxi 214023,China;Department of Hematology,Zhujiang Hospital of Southern Medical University,Guangzhou 510280,China)

机构地区：[1]复旦大学附属中山医院血液科,上海200032 [2]中山大学肿瘤防治中心血液肿瘤科,广州510060 [3]上海交通大学医学院附属新华医院血液科,200092 [4]苏州大学附属第一医院血液科,江苏省血液研究所,210056 [5]北京积水潭医院血液科,100035 [6]南京医科大学附属鼓楼医院血液科,210008 [7]安徽省肿瘤医院血液科,合肥230031 [8]厦门大学附属第一医院血液科,361003 [9]广西医科大学第一附属医院血液科,南宁530021 [10]苏州大学附属第二医院血液科,215004 [11]河北大学附属医院血液科,保定071030 [12]中国医科大学盛京医院血液科,沈阳110004 [13]无锡市人民医院血液科,214023 [14]南方医科大学珠江医院血液科,广州510280

出　　处：《中华血液学杂志》2021年第8期628-634,共7页Chinese Journal of Hematology

摘　　要：目的评估伊沙佐米、来那度胺、地塞米松(IRd)方案治疗复发/难治多发性骨髓瘤(MM)的疗效及安全性。方法纳入2018年7月至2020年5月于国内14个中心接受至少1个周期IRd方案治疗的复发/难治MM患者。除7例起始剂量作调整的患者以外,其余患者伊沙佐米起始剂量为4 mg。来那度胺剂量根据患者肌酐清除率进行调整。每周期进行疗效及安全性评估。结果共纳入74例患者,中位年龄65岁,11例(14.9%)患者曾接受>三线治疗。总体反应率(ORR)为54.1%(40/74),其中7例(9.5%)达严格意义的完全缓解或完全缓解,14例(18.9%)达非常好的部分缓解,19例(25.7%)达部分缓解,中位无进展生存时间为9.9月,中位总生存时间为20个月,中位获得反应时间为1个月。总体疗效与生存结果与TOURMALINE-MM1中国延展性研究(TOURMALINE-MM1 CCS)相近。硼替佐米难治、来那度胺难治、两药均难治患者的ORR分别为52.0%(13/25)、57.1%(4/7)和33.3%(6/18)。3~4级不良事件(AE)发生率为36.5%(27/74)。主要血液学不良反应为贫血、血小板减少、淋巴细胞减少及中性粒细胞减少。主要非血液学不良反应为乏力、消化道症状及感染。2例患者出现3级周围神经病变。与不符合TOURMALINE-MM1 CCS试验入组标准的患者相比,符合入组标准的患者ORR更高[77.8%(14/18)对46.4%(26/56),P=0.020],两组3~4级AE发生率的差异无统计学意义[33.3%(6/18)对37.5%(21/56),P=0.749]。结论IRd方案治疗复发/难治MM具有较好的疗效及安全性。Objective To evaluate the efficacy and safety profile of ixazomib/lenalidomide/dexamethasone(IRd)in Chinese patients with relapsed/refractory multiple myeloma(MM).Methods This study comprising 14 medical centers in China included patients with relapsed/refractory MM who received at least.Ixazomib at an initial oral dose of 4 mg was administered.Seven patients had dose adjustment to 3 mg at the time of first dose.The lenalidomide doses were adjusted according to creatinine clearance rate.The efficacy and safety were evaluated every cycle.Results In the study cohort of 74 patients,the median age was 65 years and 11(14.9%)patients received over three lines of therapy.Overall response rate(ORR)was 54.1%(40/74),and 7(9.5%),14(18.9%),and 19(25.7%)patients achieved stringent complete response or complete response,very good partial response,and partial response,respectively.The median progression-free survival and overall survival were 9.9 and 20 months,respectively.The median time to response was 1 month.The efficacy and survival outcome were similar to those reported in the Tourmaline-MM1 China Continuous Study.The ORR of patients refractory to bortezomib,lenalidomide,and bortezomib plus lenalidomide were 52.0%(13/25),57.1%(4/7),and 33.3%(6/18),respectively.The rate of grade 3-4 adverse events was 36.5%(27/74).Common hematological toxicities were anemia,thrombocytopenia,lymphopenia,and neutropenia.Common non-hematological toxicities were fatigue,gastrointestinal symptoms,and infections.Two cases of grade 3 peripheral neuropathy were reported.The patients eligible for the Tourmaline-MM1 China Continuous Study had a higher ORR than the ineligible patients[77.8%(14/18)vs 46.4%(26/56),P=0.020].There was no difference in the rate of grade 3-4 adverse events[33.3%(6/18)vs 37.5%(21/56),P=0.749].Conclusion The IRd regimen had good efficacy and acceptable toxicity in Chinese patients with relapsed/refractory MM.

关 键 词：多发性骨髓瘤 伊沙佐米 来那度胺 疗效 安全性 

分 类 号：R733.3[医药卫生—肿瘤]