Landgren Ola, Morgan Gareth J
Authors' Affiliations: National Cancer Institute, NIH, Center for Cancer Research, Medical Oncology Branch, Bethesda, Maryland; and The Institute of Cancer Research, Royal Cancer Hospital, London, United Kingdom.
Clin Cancer Res. 2014 Feb 15;20(4):804-13. doi: 10.1158/1078-0432.CCR-13-2159. Epub 2013 Nov 22.
Since the mid-1990s, the multiple myeloma treatment landscape has evolved considerably, which has led to improved patient outcomes and prolonged survival. In addition to discovering new, targeted agents or treatment regimens, the identification and validation of biomarkers has the potential to further improve patient outcomes. The International Staging System relies on a number of biochemical parameters to stratify patients into risk categories. Other biologically relevant markers that are indicative of inherited genetic variation (e.g., single-nucleotide polymorphisms) or tumor-acquired genetic events (e.g., chromosomal translocations or mutations) have been studied for their prognostic potential. In patients with high-risk cytogenetics, plasma cells (PC) undergo genetic shifts over time, which may partially explain why high-risk patients relapse and are so difficult to treat. Although novel agents have improved treatment outcomes, identification of markers that will enable clinicians to determine which treatment is most appropriate for high-risk patients following initial diagnosis represents an exciting frontier in the clinical management of multiple myeloma. Biomarkers based on quantitating PCs or factors that are secreted from them (e.g., serum free light chain) may also help to risk-stratify patients with asymptomatic multiple myeloma. Eventually, identification of novel biomarkers may lead to the creation of personalized treatment regimens that are optimized to target clonal PCs that express a specific oncogenomic profile. Although the future is exciting, validation will be necessary before these biologic and molecular beacons can inform decision-making processes in a routine clinical setting.
自20世纪90年代中期以来，多发性骨髓瘤的治疗格局发生了显著变化，这使得患者的治疗效果得到改善，生存期得以延长。除了发现新的靶向药物或治疗方案外，生物标志物的识别和验证有可能进一步改善患者的治疗效果。国际分期系统依靠一些生化参数将患者分层为不同的风险类别。其他与生物学相关的标志物，如指示遗传基因变异的（如单核苷酸多态性）或肿瘤获得性基因事件的（如染色体易位或突变），已就其预后潜力进行了研究。在具有高危细胞遗传学特征的患者中，浆细胞会随着时间推移发生基因变化，这可能部分解释了为什么高危患者会复发且如此难以治疗。尽管新型药物改善了治疗效果，但识别能够使临床医生在初诊后确定哪种治疗最适合高危患者的标志物，仍是多发性骨髓瘤临床管理中一个令人兴奋的前沿领域。基于定量浆细胞或其分泌因子（如血清游离轻链）的生物标志物，也可能有助于对无症状多发性骨髓瘤患者进行风险分层。最终，新型生物标志物的识别可能会带来个性化治疗方案的制定，这些方案经过优化以靶向表达特定肿瘤基因组特征的克隆性浆细胞。尽管未来令人期待，但在这些生物学和分子标志物能够为常规临床环境中的决策过程提供信息之前，还需要进行验证。
