Objective: To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform. Results: ① In 180 patients, 1q was found in 51.1% cases. Of them, 174 patients had complete follow-up data, including 88 cases with 1q and 86 without 1q (non-1q). ②Incidence of 1q was positively associated with percentage of IGH rearrangement (72.2%, P=0.017) and 1p deletion (1p) (27.8%, P=0.040). ③ The median PFS was 15.0 and 20.3 months for the 1q group and non-1q group, and the median OS was 29.4 and 44.0 months, respectively. Both PFS and OS of 1q group was significantly shorter than those of the non-1q group (P=0.029 and 0.038, respectively). Multivariate analysis further revealed that 1q was an independent prognostic factor for both PFS (HR=1.910, 95% CI 1.105-3.303, P=0.020) and OS (HR=2.353, 95% CI 1.090-5.078, P=0.029). ④ In 91 evaluable cases with 1q, very good partial remission (VGPR) rate was higher after treatment with Btz than those without Btz (62.1% vs 40.0%, P=0.032). Of note, the patients with 1q who received auto-HSCT after induction with Btz had significantly longer PFS than those without auto-HSCT (19 months vs 13 months, P=0.048). ⑤GEP analysis revealed that 1q21 amplification predominantly up-regulated expression of >50% genes within 1q21 region, and also altered expression of 28% genes in chromosome 1 and 10% genes in whole genome, particularly related to DNA repair and cell cycle. Conclusions: 1q is an independent adverse prognostic factor in patients with newly diagnosed MM. It is often associated with 1p deletion and IGH rearrangement. Patients with 1q respond well to Btz-based regimen, but they fail to gain long-term benefit from this treatment itself. However, auto-HSCT following Btz induction might improve survival of patients with 1q, suggesting a potential strategy to treat this high-risk subset of MM. GEP analysis warrants further attention in understanding the mechanisms underlying the high-risk of 1q.
目的： 探讨1q21扩增（简称1q）对硼替佐米（Btz）治疗多发性骨髓瘤（MM）疗效和预后的影响。 方法： 以2009年11月至2016年8月180例初治MM患者为研究对象，比较伴与不伴1q的MM患者的临床特征，分析其对Btz疗效及患者预后的影响，并通过R2分析平台，比较伴和不伴1q MM样本间基因表达谱的差异。 结果： ①180例患者中，男98例、女82例，中位年龄60（33~86）岁。1q发生率为51.1%（92/180），174例患者随访资料完整，其中1q组88例，无1q组86例。②1q组和无1q组伴del(1p)的发生率分别为27.8%和9.4%（χ(2)=3.71，P=0.040），伴IGH重排的发生率分别为72.2%和57.6%（χ(2)=4.09，P=0.017），差异均有统计学意义。③1q组和无1q组患者的中位无进展生存（PFS）时间分别为15.0（95% CI 15.0~22.1）、20.3（95% CI 20.7~31.2）个月，中位总生存（OS）时间分别为29.4（95% CI 28.9~38.7）、44.0（95% CI 36.4~47.6）个月，1q组较无1q组均显著缩短（P值分别为0.029、0.038），且1q为影响患者预后的独立不良因素（PFS：HR=1.910，95%CI 1.105~3.303，P=0.020；OS：HR=2.353，95%CI 1.090~5.078，P=0.029）。④伴1q患者中，Btz治疗组深度缓解率（≥非常好的部分缓解率）明显优于非Btz组（62.1%对40.0%，P=0.032），序贯auto-HSCT组较非移植组PFS期明显延长（19对13个月，P=0.048）。⑤基因表达谱分析结果显示，有1q和无1q样本的基因表达谱不同，1q上调1q21区>50%基因表达，并导致1号染色体及全基因组基因表达的异常，差异显著的基因与DNA修复和细胞周期等相关（P值均<0.001）。 结论： 1q是影响患者生存的独立预后不良因素，其常伴del（1p）和IgH重排等，Btz诱导治疗可明显提高1q患者的深度缓解率，但不改善患者的总生存，而序贯auto-HSCT巩固治疗则可能延长PFS，基因表达谱分析可能有助于解析1q高危的分子基础。.
Keywords: 1q21 amplification; Bortezomib; Hematopoietic stem cell transplantation; Multiple myeloma; Prognosis.