摘要
目的:探讨基于Dara-KRd-PACE(达雷妥尤单抗、卡非佐米、来那度胺、地塞米松、顺铂、表柔比星、环磷酰胺、依托泊苷)的诱导治疗联合自体造血干细胞移植(ASCT)在新诊断适合移植超高危(UHR)多发性骨髓瘤(MM)患者中的有效性和安全性。方法:对2023年11月—2025年9月入组国内多中心、前瞻性、Ⅱ期临床研究(NCT06140966)的患者随访数据进行分析。结果:本研究共纳入23例新诊断适合移植UHRMM患者,中位年龄54(32~69)岁,其中原发性浆细胞白血病(pPCL)患者10例(43.5%),MM伴非骨旁浸润5例(21.7%),双打击型MM 8例(34.8%)。入组患者中,R-ISS分期Ⅱ期7例(30.4%),R-ISS分期Ⅲ期15例(65.2%)。疗效分析显示:1个疗程Dara-KRd-PACE诱导治疗后(n=23),总体缓解率(ORR)为95.7%,≥非常好的部分缓解(VGPR)率为78.3%,完全缓解率(CR)率为17.4%。其中,pPCL患者(n=10),ORR为90%,≥VGPR率为50%,CR率为10.0%。2个疗程Dara-KRd-PACE后(n=18),ORR为94.4%,≥VGPR率为94.4%,CR/sCR率为38.9%,MRD阴性率为88.9%。其中,pPCL患者(n=8),ORR为100.0%,≥VGPR率为87.5%,CR/sCR率为12.5%,MRD阴性率为87.5%。完成ASCT后(n=9),≥VGPR率为88.9%,CR/sCR率为77.8%,1例(11.1%)出现疾病进展(PD),MRD阴性率为88.9%。其中,pPCL患者(n=4):≥VGPR率为100.0%,CR/sCR率为75.0%,MRD阴性率为100.0%。安全性分析显示:接受Dara-KRd-PACE诱导治疗期间,最常见的不良事件(AEs)为血液学AEs,最常见的非血液学AEs为感染。无不良反应相关的死亡。结论:基于Dara-KRd-PACE的诱导治疗联合ASCT在新诊断适合移植UHRMM患者中显示出较高的缓解率与较好耐受性,表现出潜在的治疗前景,其长期生存获益有待进一步随访证实。
Objective To evaluate the efficacy and safety of Dara-KRd-PACE(daratumumab,carfilzomib,lenalidomide,dexamethasone,cisplatin,epirubicin,cyclophosphamide,etoposide)induction therapy combined with autologous stem cell transplantation(ASCT)in newly diagnosed transplant-eligible ultra-high-risk(UHR)multiple myeloma(MM)patients.Methods Data from patients enrolled in a prospective,multicenter,phase Ⅱ clinical trial(NCT06140966)between November 2023 and September 2025 were analyzed.Results The cohort included 23 UHRMM patients with a median age of 54(32-69)years.Among them,10(43.5%)were primary plasma cell leukemia(pPCL),5(21.7%)were MM with extramedullary extraosseous,and 8 were(34.8%)double-hit MM R-ISS staging was Ⅱ in 7(30.4%)and Ⅲ in 15(65.2%).Efficacy analysis:after 1 cycle of Dara-KRd-PACE induction(n=23):overall response rate(ORR)was 95.7%,≥very good partial response(VGPR)rate was 78.3%,and complete response(CR)rate was 17.4%.For pPCL patients(n=10):ORR was 90.0%,≥VGPR rate was 50.0%,CR was 10.0%.After 2 cycles of Dara-KRd-PACE induction(n=18):ORR was 94.4%,≥VGPR rate was 94.4%,CR/stringent CR(sCR)rate was 38.9%,and the minimal residual disease(MRD)negativity(10-5)was 88.9%.For pPCL patients(n=8):ORR was 100.0%,≥VGPR rate was 87.5%,CR/sCR rate was 12.5%,MRD negativity was 87.5%.Post-ASCT(n=9):≥VGPR rate was 88.9%,CR/sCR rate was 77.8%,1 case(11.1%)had progressive disease(PD),and MRD negativity was 88.9%.For pPCL patients(n=4):≥VGPR rate was 100.0%,CR/sCR rate was 75.0%,MRD negativity was 100.0%.Safety analysis:during Dara-KRd-PACE induction,the most common adverse events(AEs)were hematologic,and the most common non-hematologic AEs were infections.No treatment-related deaths occurred.Conclusion Combining Dara-KRd-PACE induction with ASCT yielded high response rates and excellent tolerability in newly diagnosed,transplant-eligible UHRMM patients,highlighting its clinical promise.Confirmation of long-term survival benefits requires additional follow-up studies.
作者
徐健
沈恺妮
魏永强
魏小磊
李炳宗
孙秀丽
李璐
徐鹤
张立莹
李德虎
毛玥莹
徐傲霜
赵菲
傅卫军
李剑
孙春艳
XU Jian;SHEN Kaini;WEI Yongqiang;WEI Xiaolei;LI Bingzong;SUN Xiuli;LI Lu;XU He;ZHANG Liying;LI Dehu;MAO Yueying;XU Aoshuang;ZHAO Fei;FU Weijun;LI Jian;SUN Chunyan(Institute of Hematology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430022,China;Department of Hematology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College;Department of Hematology,Nanfang Hospital,Southern Medical University;Department of Hematology,the Second Affiliated Hospital of Soochow University;Department of Hematology,the First Affiliated Hospital of Dalian Medical University;Department of Hematology,Shanghai Fourth People's Hospital,School of Medicine,Tongji University)
出处
《临床血液学杂志》
2025年第11期853-859,共7页
Journal of Clinical Hematology
基金
国家自然科学基金面上项目(No:82270214、82470205)。
关键词
超高危多发性骨髓瘤
浆细胞白血病
干细胞移植
高危细胞遗传学
达雷妥尤单抗
ultra-high-risk multiple myeloma
plasma cell leukemia
stem cell transplantation
high risk cytogenetics abnormalities
daratumumab
