PDF(Pubmed)
Abstract：
Additional copies of chromosome 1 long arm (1q) are frequently found in multiple myeloma (MM) and predict high-risk disease. Available data suggest a different outcome and biology of patients with amplification (Amp1q, ≥4 copies of 1q) vs. gain (Gain1q, 3 copies of 1q) of 1q. We evaluated the impact of Amp1q/Gain1q on the outcome of newly diagnosed MM patients enrolled in the FORTE trial (NCT02203643). Among 400 patients with available 1q data, 52 (13%) had Amp1q and 129 (32%) Gain1q. After a median follow-up of 62 months, median progression-free survival (PFS) was 21.2 months in the Amp1q group, 54.9 months in Gain1q, and not reached (NR) in Normal 1q. PFS was significantly hampered by the presence of Amp1q (HR 3.34 vs. Normal 1q, P < 0.0001; HR 1.99 vs. Gain1q, P = 0.0008). Patients with Gain1q had also a significantly shorter PFS compared with Normal 1q (HR 1.68, P = 0.0031). Concomitant poor prognostic factors or the failure to achieve MRD negativity predicted a median PFS < 12 months in Amp1q patients. Carfilzomib-lenalidomide-dexamethasone plus autologous stem cell transplantation treatment improved the adverse effect of Gain1q but not Amp1q. Transcriptomic data showed that additional 1q copies were associated with deregulation in apoptosis signaling, p38 MAPK signaling, and Myc-related genes.
摘要：
在多发性骨髓瘤（MM）中经常发现1号染色体长臂（1q）的其他拷贝，并预测高风险疾病。现有数据表明扩增患者的结果和生物学不同(Amp1q，≥4份1q)vs.增益(Gain1q，3份1q)的1q。我们评估了Amp1q/Gain1q对FORTE试验(NCT02203643)新诊断MM患者预后的影响。在有1q数据的400名患者中，52（13%）的Amp1q和129（32%）的Gain1q。经过62个月的中位随访，Amp1q组的中位无进展生存期（PFS）为21.2个月，在Gain1q的54.9个月，在正常1q中未达到(NR)。Amp1q的存在显著阻碍了PFS(HR3.34vs.正常1q,P<0.0001;HR1.99vs.Gain1q,P=0.0008)。与正常1q相比，Gain1q患者的PFS也明显较短（HR1.68，P=0.0031）。伴随不良预后因素或未能达到MRD阴性预测Amp1q患者的中位PFS<12个月。卡非佐米-来那度胺-地塞米松联合自体干细胞移植治疗可改善Gain1q的不良反应，但不能改善Amp1q的不良反应。转录组数据显示，额外的1q拷贝与凋亡信号的失调有关，p38MAPK信号，和Myc相关基因.
