摘要
目的探讨新型药物治疗多发性骨髓瘤(multiple myeloma,MM)的疗效,分析预后相关影响因素及新型药物治疗对预后的影响。方法选取山东第一医科大学附属中心医院2014年2月—2024年5月收治的93例初诊多发性骨髓瘤(newly diagnosed multiple myeloma,NDMM)患者,其中11例行传统化疗,82例采用新型药物治疗,包括蛋白酶体抑制剂硼体佐米、免疫调节剂来那度胺,新药诱导治疗后序贯自体造血干细胞移植(autologous stem cell transplantation,ASCT)治疗11例,评价疗效并进行log⁃rank单因素及Cox回归多因素分析。82例NDMM患者中属于复发/难治性多发性骨髓瘤(relapsed or refractory multiple myeloma,RRMM)患者33例,使用新型药物治疗,包括免疫治疗CD38单抗,蛋白酶体抑制剂卡非佐米、伊沙佐米、硼替佐米及免疫调节剂泊马度胺、来那度胺,评价其疗效。结果82例NDMM患者新药治疗完全缓解(complete remission,CR)率24.4%,总缓解率(overall response rate,ORR)75.6%,中位无进展生存期(progression⁃free survival,PFS)35个月,中位总生存期(overall survival,OS)60个月,联合ASCT CR率63.6%,ORR 81.8%,中位OS 81.2个月;新药治疗较传统化疗ORR更高(P=0.028),联合ASCT可进一步提高OS(P=0.031)。多因素分析结果显示,双打击、初治诱导未达部分缓解(partial response,PR)及以上、未行ASCT共同影响NDMM患者PFS和OS;新型药物治疗下,33例RRMM患者CR 12.1%,ORR 57.6%,复发后中位OS 33个月,其中13例使用新一代新型药物(CD38单抗、卡非佐米、伊沙佐米、泊马度胺)中任意2种治疗,CR 15.4%,ORR 76.9%,复发后中位OS 48个月。双打击RRMM患者再治疗达PR及以上5例,其中4例使用卡非佐米联合泊马度胺、来那度胺治疗。多因素分析显示,双打击、再治疗未达PR及以上,共同影响RRMM患者复发后生存时间。结论NDMM患者选用以新药为基础的治疗方案更获益;联合ASCT可进一步提高OS。RRMM患者使用新型免疫治疗、新一代蛋白酶体抑制剂和免疫调节剂联合治疗中位生存时间更长。双打击RRMM患者使用新一代蛋白酶体抑制剂联合免疫调节剂可达更深度缓解。无论NDMM还是RRMM患者,治疗达更深层次缓解,中位生存期更长。新型药物为基础治疗下,双打击MM患者仍然预后差,生存期短。
Objective:To explore the efficacy of novel drug treatments for patients with multiple myeloma(MM),analyze prognostic factors,and evaluate the impact of these treatments on prognosis.Methods:We analyzed 93 newly diagnosed multiple myeloma(NDMM)patients,of whom 11 received traditional chemotherapy,and 82 were treated with novel drugs,including the proteasome inhibitor bortezomib and the immunomodulatory drug lenalidomide.Among them,11 patients underwent autologous hematopoietic stem cell transplantation(ASCT)after novel drug induction therapy.The efficacy of novel drugs was evaluated,and log-rank univariate analysis and Cox regression multivariate analysis were performed.Of the 82 NDMM patients,33 were relapsed or refractory multiple myeloma(RRMM)cases,treated with novel drugs such as CD38 monoclonal antibodies,proteasome inhibitors(carfilzomib,ixazomib,bortezomib),and immunomodulatory agents(pomalidomide,lenalidomide)to assess their efficacy.Results:Among the 82 NDMM patients,the complete remission(CR)rate with novel drug treatment was 24.4%,and the overall response rate(ORR)was 75.6%.The median progression-free survival(PFS)was 35 months,and the median overall survival(OS)was 60 months.For patients undergoing ASCT,the CR rate was 63.6%,ORR was 81.8%,and median OS was 81.2 months.New drug therapy showed higher ORR than traditional chemotherapy(P=0.028),and ASCT further improved OS(P=0.031).Multivariate analysis revealed that double-hit,failure to achieve partial response(PR)or better with induction therapy,and lack of ASCT independently affected PFS and OS in NDMM.Among 33 RRMM patients,the CR rate was 12.1%,ORR was 51.5%,and the median survival after relapse was 33 months.Thirteen patients treated with two next-generation drugs(CD38 monoclonal antibodies,carfilzomib,ixazomib,pomalidomide)achieved a CR rate of 15.4%,ORR of 76.9%,and median survival of 48 months.Five double-hit RRMM patients achieved PR or better,four of whom were treated with carfilzomib combined with pomalidomide or lenalidomide.Multivariate analysis showed that double-hit and failure to achieve PR or better with re-treatment significantly affected RRMM survival.Conclusion:NDMM patients benefit more from novel drug-based treatments,with ASCT further improving OS.RRMM patients have a longer median survival time with the combination treatments involving novel immune therapies,next-generation proteasome inhibitors,and immunomodulatory drugs.Double-hit patients achieve deeper mitigation with the use of next-generation proteasome inhibitors combined with immunomodulatory drugs.In both patients with NDMM and RRMM,the median survival is longer when treatment achieves deeper remission.However,double-hit MM patients still have poor prognosis and shorter survival even under novel drug-based therapies.
作者
李永菊
陈昀
赵珺
周亚伟
王顺业
王任翔
常亚丽
LI Yongju;CHEN Yun;ZHAO Jun;ZHOU Yawei;WANG Shunye;WANG Renxiang;CHANG Yali(Graduate School,Shandong First Medical University&Shandong Academy of Medical Sciences,Jinan 250117,China;Department of Hematology,Central Hospital Affiliated to Shandong First Medical University,Jinan 250013,China)
出处
《山东第一医科大学(山东省医学科学院)学报》
2025年第5期257-265,共9页
Journal of Shandong First Medical University & Shandong Academy of Medical Sciences
基金
国家自然科学基金(81372545)。
关键词
多发性骨髓瘤
新型药物
预后
双打击
自体造血干细胞移植
multiple myeloma
novel drug
prognosis
double-hit
autologous hematopoietic stem cell transplantation
