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.
1号染色体长臂额外拷贝在多发性骨髓瘤中常见，且预示高风险疾病。现有数据表明，1q扩增（Amp1q，≥4个1q拷贝）与1q获得（Gain1q，3个1q拷贝）患者的预后及生物学特征存在差异。我们通过FORTE试验（NCT02203643）评估了Amp1q/Gain1q对新诊断多发性骨髓瘤患者预后的影响。在400例具有1q数据的患者中，52例（13%）存在Amp1q，129例（32%）存在Gain1q。中位随访62个月后，Amp1q组中位无进展生存期为21.2个月，Gain1q组为54.9个月，1q正常组尚未达到。Amp1q显著损害无进展生存期（与1q正常组相比HR=3.34，P<0.0001；与Gain1q组相比HR=1.99，P=0.0008）。与1q正常组相比，Gain1q组患者的无进展生存期也显著缩短（HR=1.68，P=0.0031）。对于Amp1q患者，若同时存在其他不良预后因素或未能达到MRD阴性，则预测中位无进展生存期将短于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改善了Gain1q的不良影响，但对Amp1q无效。转录组数据显示，额外的1q拷贝与细胞凋亡信号通路、p38 MAPK信号通路及Myc相关基因的失调相关。
肿瘤(癌症)患者之家