Objective: To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China. Methods: This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival. Results: The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage Ⅰ, 259 patients (64.6%) with stage Ⅱ, and 68 patients (17.0%) with stage Ⅲ. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage Ⅰ, 95 patients (23.7%) in stage Ⅱ, 206 patients (51.4%) in stage Ⅲ, and 50 patients (12.5%) in stage Ⅳ. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage Ⅰ; 62.0 months for stage Ⅱ, 39.2 months for stage Ⅲ, and 30.3 months for stage Ⅳ; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P<0.001). Multivariate Cox regression analysis showed that stages Ⅲ and Ⅳ of the R2-ISS were independent prognostic factors for PFS (HR=2.37, 95%CI 1.30-4.30; HR=4.50, 95%CI 2.35-9.01) and OS (HR=4.20, 95%CI 1.50-11.80; HR=9.53, 95%CI 3.21-28.29). Conclusions: The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.
目的： 验证新药时代第二次修订的国际分期系统（R2-ISS）对中国适合移植新诊断多发性骨髓瘤（MM）患者的预后价值。 方法： 多中心回顾性队列研究。收集2008年6月至2018年6月国内3个中心（首都医科大学附属北京朝阳医院、中山大学附属第一医院和海军军医大学第二附属医院）共401例适合移植的新诊断MM患者资料，所有患者均接受蛋白酶体抑制剂和/或免疫调节剂为基础的诱导化疗，联合自体造血干细胞移植。收集患者基线及随访数据，进行R2-ISS重新分期，分析无进展生存（PFS）及总生存（OS）。生存数据使用Kaplan-Meier方法估计，组间生存使用log-rank检验进行比较。危险因素与生存之间的关系使用Cox比例风险模型分析。 结果： 患者中位年龄为53岁（范围25~69岁），其中男性240例（59.5%）。初诊肾功能不全患者46例（11.5%）。按照修订的国际分期系统（R-ISS）：Ⅰ期74例（18.5%），Ⅱ期259例（64.6%），Ⅲ期68例（17.0%）。根据R2-ISS重新分期后，Ⅰ期50例（12.5%），Ⅱ期95例（23.7%），Ⅲ期206例（51.4%），Ⅳ期50例（12.5%）。中位随访时间35.9个月（范围6~119个月）。R2-ISS Ⅰ~Ⅳ期患者中位PFS期分别为75.3、62.0、39.2、30.3个月；中位OS期分别为未达到，86.6、71.6、38.5个月，各分期间PFS及OS差异均有统计学意义（均P<0.001）。多因素Cox回归分析显示R2-ISS Ⅲ、Ⅳ期是PFS（HR=2.37，95%CI 1.30~4.30；HR=4.50，95%CI 2.35~9.01）和OS（HR=4.20，95%CI 1.50~11.80；HR=9.53，95%CI 3.21~28.29）的独立预后因素。 结论： R2-ISS对新药时代中国适合移植新诊断MM患者的PFS、OS具有预后价值，其普遍性仍需在不同人群中进一步验证。.