title: Proteasome inhibitors and IMiDs can overcome some high-risk cytogenetics in multiple myeloma but not gain 1q21.
abstract: Chromosomal aberrations have significant prognostic importance in multiple myeloma (MM). However, proteasome inhibitors (PI) and IMiDs may partly overcome the poor prognostic impact of some of them. In this study, we investigated a population-based consecutive cohort newly diagnosed patients with MM admitted during a defined time period to hospitals in Denmark, Norway, and Sweden. The impact of treatment modality on the prognostic importance of specific chromosomal aberration was investigated, with special reference to gain 1q21. The median follow-up of patients still alive at analysis was 40 months for the high-dose (HDT)-treated ones and 29 months for the whole population. Three hundred forty-seven patients with a known 1q21 status were included in this study. The 347 patients were divided into three groups, that is, 119 patients with the 1q21 gain, 105 patients with other aberrations (OA), that is, del(13q), del(17p), t(4,14), and/or (14;16), and 123 patients with no aberrations (NA). The groups were compared in terms of overall survival (OS), time to progression (TTP), and response. The 3-yr OS for patients with gain 1q21 was 60% compared to patients with OA 74% and NO 82% (gain 1q21 vs. NO P < 0.001; gain 1q21 vs. OA P = 0.095). If treated with PI or IMiDs, the 3-yr OS was 58% for patients with gain 1q21 compared to patients with OA 78% and NO 78%, respectively (P = 0.041, P = 0.140). In HDT patients, the 3-yr OS was 69% for patients with gain 1q21 compared to patients with OA 84% and NO 88%, respectively (P < 0.008, P = 0.600). Thus, neither HDT nor using PI or IMiDs could overcome the poor prognostic impact of gain 1q21, while these drugs and HDT seemed to improve OS in patients with OA, approaching the survival in NO. Further, gain 1q21 appears to be one of the most important poor prognostic chromosomal aberrations in multiple myeloma with current treatments. Trials using new drugs or allogeneic transplantation are warranted.
authors.affiliation: Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Hareth
authors.initials: H
authors.lastname: Nahi
authors.affiliation: KG Jebsen Center for Myeloma Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.|Department of Pathology, St Olavs Hospital, Trondheim, Norway.
authors.forename: Thea Kristin
authors.initials: TK
authors.lastname: Våtsveen
authors.affiliation: Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Lund
authors.affiliation: PharmacoEpidemiology & PharmacoEconomics (PE2), University of Groningen, Groningen, The Netherlands.|Department of Epidemiology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Bart M S
authors.initials: BM
authors.lastname: Heeg
authors.affiliation: Department of Pathology, Odense University Hospital, Odense, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Preiss
authors.affiliation: Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Evren
authors.initials: E
authors.lastname: Alici
authors.affiliation: Department of Pathology, Odense University Hospital, Odense, Denmark.
authors.forename: Michael Boe
authors.initials: MB
authors.lastname: Møller
authors.affiliation: KG Jebsen Center for Myeloma Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.|Department of Oncology, St Olavs Hospital, Trondheim, Norway.
authors.forename: Karin Fahl
authors.initials: KF
authors.lastname: Wader
authors.affiliation: Department of Pathology, Odense University Hospital, Odense, Denmark.
authors.forename: Hanne E H
authors.initials: HE
authors.lastname: Møller
authors.affiliation: KG Jebsen Center for Myeloma Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.|Department of Hematology, St Olavs Hospital, Trondheim, Norway.
authors.forename: Lill Anny
authors.initials: LA
authors.lastname: Grøseth
authors.affiliation: Department of Hematology, Odense University Hospital, Odense, Denmark.
authors.forename: Brian
authors.initials: B
authors.lastname: Østergaard
authors.affiliation: Department of Pathology, St Olavs Hospital, Trondheim, Norway.
authors.forename: Hong Yan
authors.initials: HY
authors.lastname: Dai
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Holmberg
authors.affiliation: Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Gösta
authors.initials: G
authors.lastname: Gahrton
authors.affiliation: KG Jebsen Center for Myeloma Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.|Department of Hematology, St Olavs Hospital, Trondheim, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Waage
authors.affiliation: Department of Hematology, Odense University Hospital, Odense, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Abildgaard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D061988:Proteasome Inhibitors / Q000008:administration & dosage*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D061988:Proteasome Inhibitors
keywords: chromosomal abberation; clinical; gain 1q21; multiple myeloma