国产硼替佐米联合来那度胺、地塞米松治疗初治多发性骨髓瘤的多中心、前瞻性、Ⅱ期、单臂研究  

A multicenter, prospective, phaseⅡ, single-arm study on the treatment of newly diagnosed multiple myeloma with domestic bortezomib in combination with lenalidomide and dexamethasone

作　　者：解琳娜 王鑫 贺强 王慧 马骥 张海燕[2] 刘南[3] 接贵涛 肖太武[5] 张颢[6] 张海国[7] 李增军[1] 邢立杰 Xie Linna;Wang Xin;He Qiang;Wang Hui;Ma Ji;Zhang Haiyan;Liu Nan;Jie Guitao;Xiao Taiwu;Zhang Hao;Zhang Haiguo;Li Zengjun;Xing Lijie(Department of Lymphohematology,Cancer Hospital of Shandong First Medical University,Shandong Cancer Hospital,Jinan 250000,China;Department of Hematology,Linyi City People's Hospital,Linyi 276003,China;Department of Hematology,Heze City Hospital,Heze 274031,China;Department of Hematology,Linyi Central Hospital,Linyi 276400,China;Department of Hematology,Liaocheng City People's Hospital,Liaocheng 252000,China;Department of Hematology,Jining Medical University Affiliated Hospital,Jining 272100,China;Department of Hematology,Jining First People's Hospital,Jining 272011,China)

机构地区：[1]山东第一医科大学附属肿瘤医院,山东省肿瘤医院淋巴血液病区,济南250000 [2]临沂市人民医院血液科,临沂276003 [3]菏泽市立医院血液科,菏泽274031 [4]临沂市中心医院血液科,临沂276400 [5]聊城市人民医院血液科,聊城252000 [6]济宁医学院附属医院血液科,济宁272100 [7]济宁市第一人民医院血液科,济宁272011

出　　处：《中华血液学杂志》2024年第6期571-576,共6页Chinese Journal of Hematology

基　　金：山东省肿瘤医院启动资金(RCYJ201902);中国临床肿瘤学科学基金(Y-SY201901-0011);山东省自然科学基金面上项目(ZR2021MH072);国家自然科学基金(82200224);73批博士后基金(2023M732124);山东省优秀青年科学基金(海外)(2023HWYQ-115)。

摘　　要：目的:探索国产硼替佐米联合来那度胺及地塞米松治疗初治多发性骨髓瘤(NDMM)的疗效和安全性。方法:此项多中心、前瞻性、单臂临床研究纳入2019年12月至2022年1月7所医院收治的126例NDMM患者,均接受国产硼替佐米联合来那度胺、地塞米松方案(BLD方案)治疗,分析其疗效、预后影响因素及安全性。结果:126例NDMM患者中,118例患者完成4个周期治疗,其中118例的总体反应率(ORR)为93.22%(110/118),≥非常好的部分缓解(VGPR)率为68.64%(81/118)。114例患者完成至少8个周期治疗,ORR为92.98%(106/114),≥VGPR率为77.19%(88/114)。18例在完成6~8个周期BLD方案治疗后进行自体造血干细胞移植,ORR为100%(18/18),≥VGPR率为88.9%(16/18)。治疗疗程增加与患者≥VGPR率升高呈正相关,且分期和年龄等因素对疗效无显著影响。单因素分析显示,R2-ISS分期Ⅲ期/Ⅳ期、血钙>2.27 mmol/L、6个周期疗效未达VGPR是无进展生存(PFS)的不良预后因素(P均<0.05),6个周期未达VGPR是OS的不良预后因素(P<0.001)。多因素分析显示,6个周期未达VGPR是PFS较差的独立预后因素(P=0.002)。血液学不良反应发生率为16.7%(19/114),非血液学不良反应主要为轻度至中度,未发现明显心脏及肾脏不良反应。结论:BLD方案治疗NDMM效果显著,具有高危遗传学特征的患者仍可获得较高的≥VGPR率,且整体安全性良好。Objective To explore the efficacy and safety of domestic bortezomib in combination with lenalidomide and dexamethasone in the treatment of newly diagnosed multiple myeloma(NDMM).Methods This multicenter,prospective,single-arm clinical study included 126 patients with NDMM admitted to seven hospitals between December 2019 and January 2022.All patients received domestic bortezomib in combination with lenalidomide and dexamethasone(BLD regimen),and the efficacy,prognostic factors,and safety were analyzed.Results Among the 126 patients with NDMM,118 completed four cycles of treatment,with an overall response rate(ORR)of 93.22%(110/118)and a≥very good partial response(VGPR)rate of 68.64%(81/118).Ultimately,114 patients completed at least eight cycles of treatment,with an ORR of 92.98%(106/114)and a≥VGPR rate of 77.19%(88/114).Eighteen patients underwent autologous hematopoietic stem cell transplantation after completing 6-8 cycles of the BLD regimen,with an ORR of 100%(18/18)and a≥VGPR rate of 88.9%(16/18).The proportion of patients achieving≥VGPR increased with the treatment duration,and factors such as staging and age did not significantly affect efficacy.Single-factor analysis showed that R2-ISS stageⅢ/Ⅳ,blood calcium>2.27 mmol/L,and failure to achieve VGPR after six cycles were adverse prognostic factors for progression-free survival(PFS)(P<0.05),whereas failure to achieve VGPR after six cycles was an adverse prognostic factor for overall survival(OS)(P<0.001).Multifactor analysis demonstrated that failure to achieve VGPR after six cycles is an independent adverse prognostic factor for PFS(P=0.002).The incidence of hematologic adverse reactions was 16.7%(19/114),and nonhematologic adverse reactions were mainly mild to moderate,with no significant cardiac or renal adverse reactions observed.Conclusion The BLD regimen is effective in treating NDMM,in which patients with high-risk genetic features are still achieving a high≥VGPR rate,and the overall safety is good.

关 键 词：多发性骨髓瘤 硼替佐米 来那度胺 

分 类 号：R733.3[医药卫生—肿瘤]