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) (χ2=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 (χ2=22.74; P<0.001), respectively, among which patients in the PI/IMiD and PI+IMiD groups had comparable 2ndPFS (χ2=1.76; P=0.923). Patients with high-risk cytogenetic abnormalities (HRCAs) achieved the longest 2ndPFS of 22.0 months in the immunotherapy group (χ2=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.
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）（χ2=24.55，P<0.001），中位2ndPFS期分别为17.7、9.0、9.2、4.6个月（χ2=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（χ2=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）（χ2=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。.