Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Cancer. 2011 Mar 1;117(5):1001-9. doi: 10.1002/cncr.25535. Epub 2010 Oct 13.
Myeloma survival varies markedly with International Staging System classification, presence of cytogenetic abnormalities, and, especially, gene expression profiling-based risk and delTP53 status, whose collective impact has not been examined in the context of specific therapies.
The authors examined overall survival (OS), event-free survival (EFS), and complete response duration (CRD) in Total Therapy 2 with randomization to a control or thalidomide arm and in Total Therapy 3 with added bortezomib. Among 612 patients with complete data sets, multivariate analyses were used to investigate the relative contributions to OS, EFS, and CRD of International Staging System stage, cytogenetic abnormalities, and gene expression profiling-derived risk and delTP53 status, in the context of the 3 Total Therapy regimens.
Whereas gene expression profiling risk segregated outcomes within all 3 International Staging System stages, International Staging System 3 conferred inferior prognosis only in low-risk myeloma, whereas the grave prognosis of high-risk disease was International Staging System-independent. After adjusting for gene expression profiling-defined high risk and delTP53 in multivariate analysis, International Staging System 3 and cytogenetic abnormalities both retained independent adverse implications for OS, EFS, and CRD. Among the 86% with low-risk disease, cytogenetic abnormalities and delTP53 both affected all 3 endpoints negatively, whereas the International Staging System 3 effect was limited to OS. Total Therapy 3 improved survival outcomes beyond results obtained with Total Therapy 2.
In the genomic era, standard laboratory variables, such as International Staging System stage and presence of cytogenetic abnormalities, continue to impact survival after adjusting for gene expression profiling risk and delTP53 status, providing a basis for stratification in our current practice of gene expression profiling risk-based treatment assignment.
骨髓瘤的存活率因国际分期系统（ISS）分类、细胞遗传学异常的存在，以及基因表达谱风险和 delTP53 状态而有显著差异，这些因素的综合影响在特定治疗方案的背景下尚未得到研究。
作者分析了随机分为对照组或沙利度胺组的总治疗 2 期（Total Therapy 2）和增加硼替佐米的总治疗 3 期（Total Therapy 3）临床试验中，612 例患者的总生存（OS）、无事件生存（EFS）和完全缓解持续时间（CRD）。对于完整数据集的 612 例患者，采用多变量分析来探讨 ISS 分期、细胞遗传学异常和基因表达谱风险及 delTP53 状态在 3 种总治疗方案背景下，对 OS、EFS 和 CRD 的相对影响。
虽然基因表达谱风险在所有 3 个 ISS 分期中都能区分结局，但 ISS3 仅在低危骨髓瘤中预后较差，而高危疾病的严重预后与 ISS 无关。在多变量分析中调整基因表达谱定义的高危和 delTP53 后，ISS3 和细胞遗传学异常均对 OS、EFS 和 CRD 有独立的不利影响。在 86%的低危患者中，细胞遗传学异常和 delTP53 均对所有 3 个终点产生负面影响，而 ISS3 的影响仅局限于 OS。总治疗 3 期（Total Therapy 3）的生存结果优于总治疗 2 期（Total Therapy 2）。
在基因组时代，标准实验室变量，如 ISS 分期和细胞遗传学异常的存在，在调整基因表达谱风险和 delTP53 状态后，继续影响生存，为我们目前基于基因表达谱风险进行治疗分配的实践提供了分层的依据。
