title: Chromosome 1q21 gains confer inferior outcomes in multiple myeloma treated with bortezomib but copy number variation and percentage of plasma cells involved have no additional prognostic value.
abstract: Chromosome 1q21 aberrations have not been yet been made part of routine clinical tests and their effect in multiple myeloma is still under investigation. The prognostic value of copy number variation and percentage of plasma cells involved have remained unclear. In the present study, we analyzed the prognostic value of 1q21 in a series of 290 cases of newly diagnosed multiple myeloma treated in a prospective, non-randomized clinical trial (BDH 2008/02). We found that incidence of 1q21 aberration increased at relapse, but its copy numbers and proportion of cells involved did not change. Gains of 1q21 had no impact on survival in patients receiving thalidomide-based treatment but conferred a significantly inferior prognosis in patients under bortezomib-based chemotherapy and was an independent adverse prognostic factor for progression free survival (HR 3.831; 95%CI: 2.125-6.907; P<0.001) and overall survival (HR 3.245; 95%CI: 1.555-6.773; P=0.002). Strikingly, our results showed that the copy number variation and clone size harboring 1q21 gains carried no additional prognostic value and patients with 1q21 gains did not benefit significantly from regimens incorporating bortezomib. Our results indicate that three copies of 1q21 and 20% of plasma cells with this abnormality were enough to confer bortezomib resistance. Therefore, chromosome 1q21 gains should be considered a high-risk feature in multiple myeloma receiving bortezomib therapy.
authors.affiliation: drqiu99@medmail.com.cn.
authors.forename: Gang
authors.initials: G
authors.lastname: An
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Lihui
authors.initials: L
authors.lastname: Shi
authors.forename: Zhong
authors.initials: Z
authors.lastname: Shizhen
authors.forename: Shuhui
authors.initials: S
authors.lastname: Deng
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Xie
authors.forename: Weiwei
authors.initials: W
authors.lastname: Sui
authors.forename: Fenghuang
authors.initials: F
authors.lastname: Zhan
authors.forename: Lugui
authors.initials: L
authors.lastname: Qiu
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D018628:Gene Dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D010950:Plasma Cells; D011719:Pyrazines / Q000008:administration & dosage*; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib