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
- Author:
Xue Lian LIU
1
;
Pei Yu YANG
;
Xiao Yuan YU
;
Jing Cheng CHEN
;
Xiao Liang LIU
;
Jing BAI
;
Ying Min LIU
;
Hua HE
;
Jing Nan SUN
;
Hong Qiong FAN
;
Chen ZHANG
;
Ye ZHANG
;
Ke Ju SU
;
Chun Shui LIU
;
Ye Hui TAN
;
Su Jun GAO
;
Wei LI
;
Feng Yan JIN
Author Information
1. Department of Hematology, Cancer Center, the First Hospital of Jilin University, Changchun 130012, China.
- Publication Type:Journal Article
- Keywords:
1q21 amplification;
Bortezomib;
Hematopoietic stem cell transplantation;
Multiple myeloma;
Prognosis
- MeSH:
Bortezomib/therapeutic use*;
Chromosome Aberrations;
Humans;
Multiple Myeloma/drug therapy*;
Prognosis;
Retrospective Studies
- 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.
