Vangsted A J, Helm-Petersen S, Cowland J B, Jensen P B, Gimsing P, Barlogie B, Knudsen S
Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Granulocyte Research Laboratory, Copenhagen University Hospital, Copenhagen, Denmark.
Gene. 2018 Feb 20;644:80-86. doi: 10.1016/j.gene.2017.10.071. Epub 2017 Nov 6.
A Drug Response Prediction (DRP) score was developed based on gene expression profiling (GEP) from cell lines and tumor samples. Twenty percent of high-risk patients by GEP70 treated in Total Therapy 2 and 3A have a progression-free survival (PFS) of more than 10years. We used available GEP data from high-risk patients by GEP70 at diagnosis from Total Therapy 2 and 3A to predict the response by the DRP score of drugs used in the treatment of myeloma patients. The DRP score stratified patients further. High-risk myeloma with a predicted sensitivity to melphalan by the DRP score had a prolonged PFS, HR=2.4 (1.2-4.9, P=0.014) and those with predicted sensitivity to bortezomib had a HR 5.7 (1.2-27, P=0.027). In case of predicted sensitivity to bortezomib, a better response to treatment was found (P=0.022). This method may provide us with a tool for identifying candidates for effective personalized medicine and spare potential non-responders from suffering toxicity.
基于细胞系和肿瘤样本的基因表达谱（GEP）开发了一种药物反应预测（DRP）评分。在总治疗方案2和3A中接受治疗的GEP70高危患者中，20%的患者无进展生存期（PFS）超过10年。我们使用了总治疗方案2和3A中诊断时GEP70高危患者的可用GEP数据，通过DRP评分预测骨髓瘤患者治疗中所用药物的反应。DRP评分进一步对患者进行了分层。DRP评分预测对美法仑敏感的高危骨髓瘤患者PFS延长，风险比（HR）=2.4（1.2 - 4.9，P = 0.014），预测对硼替佐米敏感的患者HR为5.7（1.2 - 27，P = 0.027）。在预测对硼替佐米敏感的情况下，发现对治疗的反应更好（P = 0.022）。这种方法可能为我们提供一种工具，用于识别有效的个性化药物候选者，并使潜在的无反应者免受毒性影响。
