Objective: To investigate the prognostic value of the Second Revision of the International Staging System (R2-ISS) in patients with newly diagnosed multiple myeloma (NDMM) . Methods: The retrospective study was performed in 326 NDMM patients with immunomodulatory drugs and/or proteasome inhibitors as the first-line treatment attending the Department of Hematology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China, from December 2012 to March 2022. The Kaplan-Meier method was used for the survival analysis, with the Log-rank test comparing the between-group differences and Cox proportional risk regression modeling A multifactorial analysis was performed. Results: ①326 patients were included in the study, 190 of whom were males. The median age was 63 years, and the median followup time was 37 months. R2-ISS can effectively predict prognosis, particularly for R-ISS Ⅱ patients. The median progression-free survival (PFS) time of R2-ISS Ⅰ, R2-ISS Ⅱ, R2-ISS Ⅲ, and R2-ISS Ⅳ was 52, 29, 20, and 15 months (P<0.001), while the median overall survival (OS) time was 91, 60, 44, and 36 months (P<0.001). Multifactor analysis revealed that ISS Ⅱ, ISS Ⅲ, del (17p), t (4;14), 1q+, LDH increased, and age >65 years old were independent negative prognostic factors for OS. ISS Ⅱ, ISS Ⅲ, del (17p), t (4;14), 1q+, and LDH were independent negative prognostic factors for PFS. ②The C-index score of R2-ISS was 0.724, higher than that of R-ISS (0.678), indicating high prediction efficiency. ③The median PFS for 1q+-related double-hit in R2-ISS Ⅲ and Ⅳ were 20, 15 months (P=0.084) and the median OS were 35, 36 months (P=0.786), respectively. In R2-ISS Ⅲ, there were twenty-seven cases of 1q+-related double-hit, sixty-one cases of 1q+ single abnormality, and sixty-eight cases with no 1q+. The median PFS for the three groups were 20, 18, and 21 months (P=0.974), while the median OS was 35, 47, and 56 months (P=0.042), respectively. Adjusting the assignment of 1q+ to 1, the median PFS and OS of different R2-ISS stages differed significantly after regrouping (P<0.001) . Conclusions: The prognostic stratification value of R2-ISS is higher than R-ISS, particularly in the highly heterogeneous R-ISS Ⅱ population. Adjusting the assignment of the 1q+-related double-hit can improve R2-ISS, which should be validated in future studies with multi-center and expanded cases.
目的： 探讨R2-ISS（The Second Revision of the International Staging System）分期在新诊断多发性骨髓瘤（NDMM）患者中的预后价值。 方法： 收集自2012年12月至2022年3月在南京医科大学鼓楼临床医学院血液科就诊的326例以免疫调节药物和（或）蛋白酶体抑制剂为一线治疗方案的NDMM患者临床资料，采用Kaplan-Meier法进行生存分析，Log-rank检验比较组间差异，Cox比例风险回归模型进行多因素分析。 结果： ①326例NDMM患者中男性190例，中位年龄63岁，中位随访时间37个月。R2-ISS分期可进行有效的预后分层，特别是R-ISS Ⅱ期患者，R2-ISS Ⅰ期、Ⅱ期、Ⅲ期和Ⅳ期患者的中位无进展生存（PFS）期分别为52、29、20和15个月（P<0.001），中位总生存（OS）期分别为91、60、44和36个月（P<0.001）。多因素分析显示ISS Ⅱ期、ISS Ⅲ期、del（17p）、t（4；14）、1q+、LDH升高、年龄>65岁是影响OS的独立不良预后因素；ISS Ⅱ期、ISS Ⅲ期、del（17p） 、t（4；14）、1q+、LDH升高是影响PFS的独立不良预后因素。②R2-ISS分期C-index得分为0.724，优于R-ISS分期的0.678，预测效能更高。③R2-ISS Ⅲ期和Ⅳ期中含1q+在内的双打击患者中位PFS期分别为20、15个月（P＝0.084），中位OS期为35、36个月（P＝0.786）。Ⅲ期中含1q+在内的双打击27例、1q+单一异常61例、不含1q+ 68例，三组的中位PFS期分别为20、18、21个月（P＝0.974），中位OS期分别为35、47、56个月（P＝0.042）。因此本研究将1q+赋值调整至1，重新分组后R2-ISS不同分期的中位PFS期和OS期差异均有统计学意义（P<0.001）。 结论： R2-ISS分期预后分层价值优于R-ISS分期，特别是对异质性较强的R-ISS Ⅱ期人群，调整含1q+在内的双打击赋值后可进一步优化R2-ISS分期。.
Keywords: 1q gain/amplification; Double-hit; Multiple myeloma; Prognosis; Second Revision of the International Staging System.