Challenging the concept of functional high-risk myeloma through transcriptional and genetic profiling.

To establish the true incidenceof FHR, we analyzed uniformly treated, transplant-eligible patients from the Myeloma-XI (MyXI) trial that had been profiled for the International Myeloma Society and Working Group (IMS/IMWG) defined high-risk cytogenetic aberrations (HRCA), and the SKY92 gene expression HR signature (GEP-HR).

为了确定FHR的真实发生率，我们分析了来自Myeloma-XI（MyXI）试验的均一治疗、适合移植的患者，这些患者已经根据国际骨髓瘤学会和工作组（IMS/IMWG）定义的高风险细胞遗传学异常（HRCA）以及SKY92基因表达高风险特征（GEP-HR）进行了分型。

A total of 135 MyXI patients were studied, with a median follow-up of 88 months; 25 (18.5%) experienced ER, defined as relapse <18 months from maintenance randomization post-autologous stem-cell transplantation.

共研究了135例MyXI患者，中位随访时间为88个月；其中25例（18.5%）经历了早期复发（ER），定义为自体干细胞移植后维持随机化<18个月的复发。

Hereof, 15 (60%) were IMS/IMWG-HR at diagnosis, of whom 8 were also GEP-HR.

其中15例（60%）在诊断时为IMS/IMWG-HR，其中8例同时为GEP-HR。

Another 6 patients were GEP-HR only and would have been missed by IMS/IMWG-HR.

另外6名患者仅被GEP-HR识别，如果仅使用IMS/IMWG-HR标准则会被遗漏。

Among 4 patients with IMS/IMWG- and GEP-standard risk, 2 had isolated HR markers at diagnosis, leaving only 2 patients (8% of ER; 1.5% of all) truly meeting all FHR-criteria.

在4名被IMS/IMWG-和GEP标准识别为标准风险的患者中，有2人在诊断时仅表现出高风险标记，这使得只有2名患者（占ER的8%；占所有患者的1.5%）真正符合所有FHR标准。

Combined IMS/IMWG-HR and GEP-HR profiling identified 84% of ER, and differentiated long-term outcome across all 135 patients: co-occurring IMS/IMWG and GEP-HR was associated with very short overall survivalcompared to the absence of both (HR = 13.1; 95% CI, 6.5-26.1, P < .0001), followed by GEP-HR only (HR = 5.1; 95% CI, 2.4-11.1, P < .0001) and IMS/IMWG-HR only (HR = 3.2; 95% CI, 1.6-6.2, P = .0007).

综合IMS/IMWG-HR和GEP-HR分型，我们识别出84%的ER，并对所有135名患者进行了长期预后的区分：同时出现IMS/IMWG和GEP-HR的患者总生存期非常短，与两者均未出现的患者相比（HR = 13.1；95%置信区间，6.5-26.1，P < .0001），其次是仅GEP-HR（HR = 5.1；95%置信区间，2.4-11.1，P < .0001）和仅IMS/IMWG-HR（HR = 3.2；95%置信区间，1.6-6.2，P = .0007）。

Our results support more comprehensive baseline diagnostic profiling to identify those at risk of ER upfront.

我们的结果支持在基线时进行更全面的诊断分型，以便提前识别出有ER风险的患者。

The trials were registered at the ISRCTN Registry as ISRCTN49407852 and at clinicaltrials.gov as #NCT01554852.

这些试验已在ISRCTN注册处注册为ISRCTN49407852，在clinicaltrials.gov注册为#NCT01554852。