Effect of 1q21 amplification on bortezomib therapeutic response and prognosis of newly diagnosed multiple myeloma patients
10.3760/cma.j.issn.0253-2727.2018.05.013
- VernacularTitle: 1q21扩增对硼替佐米治疗初治多发性骨髓瘤患者疗效和预后的影响
- Author:
Xuelian LIU
1
;
Peiyu YANG
;
Xiaoyuan YU
;
Jingcheng CHEN
;
Xiaoliang LIU
;
Jing BAI
;
Yingmin LIU
;
Hua HE
;
Jingnan SUN
;
Hongqiong FAN
;
Chen ZHANG
;
Ye ZHANG
;
Keju SU
;
Chunshui LIU
;
Yehui TAN
;
Sujun GAO
;
Wei LI
;
Fengyan JIN
Author Information
1. Department of Hematology, Cancer Center, the First Hospital of Jilin University, Changchun 130012, China
- Publication Type:Journal Article
- Keywords:
Multiple myeloma;
1q21 amplification;
Bortezomib;
Hematopoietic stem cell transplantation;
Prognosis
- From:
Chinese Journal of Hematology
2018;39(5):408-413
- CountryChina
- Language:Chinese
-
Abstract:
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.
