BCD方案治疗后首次复发多发性骨髓瘤的方案选择及预后因素分析

Efficacy of different regimens and prognostic factors in patients with first relapsed multiple myeloma treated after front-line bortezomib,cyclophosphamide,and dexamethasone

目的分析多发性骨髓瘤(MM)患者一线采用硼替佐米、环磷酰胺、地塞米松(BCD)方案诱导治疗后首次复发采用不同二线治疗方案的疗效及预后因素。方法回顾性队列研究。收集2009年7月至2022年10月以北京协和医院为主的北方地区3家医院的经BCD方案诱导治疗后首次复发的MM患者,根据二线化疗方案将患者分为4组:免疫治疗组(包含达雷妥尤单抗、嵌合抗原受体T细胞免疫疗法的方案)、1种新药治疗组[包含蛋白酶体抑制剂(PI)或免疫调节剂(IMiD)之一,PI或IMiD组]、2种新药联合治疗组(同时应用PI和IMiD,PI+IMiD组)、传统化疗或姑息组。比较4组患者疗效、二线治疗无进展生存(2ndPFS)期和总生存(OS)期,并分析2ndPFS的影响因素。用Kaplan-Meier法进行生存分析,用Cox比例风险模型进行单因素和多因素分析。结果共纳入217例MM患者,中位年龄62岁(范围31~83岁),男性占56.2%(122/217),二线化疗方案比率分别为免疫治疗8.8%(19例)、PI或IMiD治疗48.4%(105例)、PI+IMiD治疗29.9%(65例)、传统化疗或姑息支持12.9%(28例)。免疫治疗组、PI或IMiD组、PI+IMiD组及传统化疗或姑息组的二线化疗后总反应率(ORR)分别为94.7%(18/19)、56.2%(59/105)、73.8%(48/65)、32.1%(9/28)(χ^(2)=24.55,P<0.001),中位2ndPFS期分别为17.7、9.0、9.2、4.6个月(χ^(2)=22.74,P<0.001),4组间差异有统计学意义,其中PI或IMiD组与PI+IMiD组2ndPFS相似(χ^(2)=1.76,P=0.923)。亚组分析显示,诊断时具有高危细胞遗传学异常的患者,首次复发时采用免疫治疗的2ndPFS最长(22.0个月)(χ^(2)=15.03,P=0.002)。多因素分析显示,二线方案选择免疫治疗(HR=0.11,95%CI 0.05~0.27)、最佳疗效达部分缓解及以上(HR=0.47,95%CI 0.34~0.66)、非侵袭性复发(HR=0.25,95%CI 0.17~0.37)为影响2ndPFS的独立因素。结论真实世界数据显示,一线BCD方案治疗后首次复发的MM患者,二线方案选择免疫治疗可获得更深的缓解和更长的无进展生存期,对基线具有高危细胞遗传学异常的患者亦是如此。

Objective To analyze the efficacy of second-line regimens and prognostic factors in patients with first-relapsed multiple myeloma(MM)treated with bortezomib,cyclophosphamide,and dexamethasone(BCD).Methods A retrospective cohort study.Clinical data were collected in first-relapsed MM patients after BCD treatment from three tertiary hospitals in north China from July 2009 to October 2022.Patients were classified according to the second-line regimen into the immunotherapy group,single novel agent group[either proteasome inhibitor(PI)or immunomodulatory drug(IMiD)],combination treatment group(both PI+IMiD),and traditional treatment group.Responses to second-line regimens and survival data were analyzed.The Kaplan-Meier method was used for survival analysis and the Cox proportional risk model was used for univariate and multivariate analyses.Results A total of 217 patients were enrolled including 8.8%(19/217)in the immunotherapy group,48.4%(105/217)in the PI/IMiD group,29.9%(65/217)in the PI+IMiD group,and 12.9%(28/217)in the traditional treatment group.The median age was 62 years(range 31-83 years)and 56.2%(122/217)were males.The overall response rates(ORRs)in the four groups were 94.7%(18/19)vs.56.2%(59/105)vs.73.8%(48/65)vs.32.1%(9/28)(χ^(2)=24.55;P<0.001),respectively.The progression-free survival(PFS)of the second-line regimens(2ndPFS)was 17.7 vs.9.0 vs.9.2 vs.4.6 months(χ^(2)=22.74;P<0.001),respectively,among which patients in the PI/IMiD and PI+IMiD groups had comparable 2ndPFS(χ^(2)=1.76;P=0.923).Patients with high-risk cytogenetic abnormalities(HRCAs)achieved the longest 2ndPFS of 22.0 months in the immunotherapy group(χ^(2)=15.03;P=0.002).Multivariate analysis suggested that immunotherapy(HR=0.11,95%CI 0.05-0.27),achievement of efficacy of partial response or better(HR=0.47,95%CI 0.34-0.66),and non-aggressive relapse(HR=0.25,95%CI 0.17-0.37)were independent prognostic factors of 2ndPFS.Conclusion In this real-world study,immunotherapy was associated with a more favorable efficacy and PFS for first-relapsed MM patients after BCD treatment,with similar outcomes in patients with HRCAs.