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 （1q） 的额外拷贝常见于多发性骨髓瘤 （MM） 中，可预测高危疾病。现有数据表明，扩增 （Amp1q，≥1q 的 4 个拷贝） 与 1q 的增益 （Gain1q，1q 的 3 个拷贝） 患者的结局和生物学特性不同。我们评估了 Amp1q/Gain1q 对参加 FORTE 试验的新诊断 MM 患者预后的影响 （NCT02203643。在有可用 1q 数据的 400 名患者中，52 名 （13%） 患有 Amp1q，129 名 （32%） 患有 Gain1q。中位随访 62 个月后，Amp1q 组的中位无进展生存期 （PFS） 为 21.2 个月，Gain1q 为 54.9 个月，正常 1q 未达到 （NR）。Amp1q 的存在显著阻碍了 PFS （HR 3.34 vs. 正常 1q，P < 0.0001;HR 1.99 vs. Gain1q，P = 0.0008）。与正常 1q 相比，Gain1q 患者的 PFS 也显著缩短 （HR 1.68，P = 0.0031）。 伴随的不良预后因素或未能达到 MRD 阴性预测 Amp1q 患者 12 个月的中位 PFS <。卡非佐米 - 来那度胺 - 地塞米松加自体干细胞移植治疗改善了 Gain1q 的不良反应，但没有改善 Amp1q 的不良反应。转录组学数据显示，额外的 1q 拷贝与细胞凋亡信号传导、 p38 MAPK 信号传导和 Myc 相关基因的失调有关。