Proteasome inhibitors and IMiDs can overcome some high-risk cytogenetics in multiple myeloma but not gain 1q21

Hareth Nahi, Thea Kristin Våtsveen, Johan Lund, Bart M S Heeg, Birgitte Preiss, Evren Alici, Michael Boe Møller, Karin Fahl Wader, Hanne E H Møller, Lill Anny Grøseth, Brian Østergaard, Hong Yan Dai, Erik Holmberg, Gösta Gahrton, Anders Waage, Niels Abildgaard

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftEuropean Journal of Haematology
Vol/bind96
Udgave nummer1
Sider (fra-til)46-54
ISSN0902-4441
DOI
StatusUdgivet - 2016

Fingeraftryk

Proteasome Inhibitors
Cytogenetics
Denmark
Norway
Pharmaceutical Preparations
Population

Citer dette

Nahi, Hareth ; Våtsveen, Thea Kristin ; Lund, Johan ; Heeg, Bart M S ; Preiss, Birgitte ; Alici, Evren ; Møller, Michael Boe ; Wader, Karin Fahl ; Møller, Hanne E H ; Grøseth, Lill Anny ; Østergaard, Brian ; Dai, Hong Yan ; Holmberg, Erik ; Gahrton, Gösta ; Waage, Anders ; Abildgaard, Niels. / Proteasome inhibitors and IMiDs can overcome some high-risk cytogenetics in multiple myeloma but not gain 1q21. I: European Journal of Haematology. 2016 ; Bind 96, Nr. 1. s. 46-54.
@article{70ff15db31f845958434768c360e93d2,
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.",
author = "Hareth Nahi and V{\aa}tsveen, {Thea Kristin} and Johan Lund and Heeg, {Bart M S} and Birgitte Preiss and Evren Alici and M{\o}ller, {Michael Boe} and Wader, {Karin Fahl} and M{\o}ller, {Hanne E H} and Gr{\o}seth, {Lill Anny} and Brian {\O}stergaard and Dai, {Hong Yan} and Erik Holmberg and G{\"o}sta Gahrton and Anders Waage and Niels Abildgaard",
note = "{\circledC} 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.",
year = "2016",
doi = "10.1111/ejh.12546",
language = "English",
volume = "96",
pages = "46--54",
journal = "European Journal of Haematology",
issn = "0902-4441",
publisher = "Wiley-Blackwell",
number = "1",

}

Nahi, H, Våtsveen, TK, Lund, J, Heeg, BMS, Preiss, B, Alici, E, Møller, MB, Wader, KF, Møller, HEH, Grøseth, LA, Østergaard, B, Dai, HY, Holmberg, E, Gahrton, G, Waage, A & Abildgaard, N 2016, 'Proteasome inhibitors and IMiDs can overcome some high-risk cytogenetics in multiple myeloma but not gain 1q21', European Journal of Haematology, bind 96, nr. 1, s. 46-54. https://doi.org/10.1111/ejh.12546

Proteasome inhibitors and IMiDs can overcome some high-risk cytogenetics in multiple myeloma but not gain 1q21. / Nahi, Hareth; Våtsveen, Thea Kristin; Lund, Johan; Heeg, Bart M S; Preiss, Birgitte; Alici, Evren; Møller, Michael Boe; Wader, Karin Fahl; Møller, Hanne E H; Grøseth, Lill Anny; Østergaard, Brian; Dai, Hong Yan; Holmberg, Erik; Gahrton, Gösta; Waage, Anders; Abildgaard, Niels.

I: European Journal of Haematology, Bind 96, Nr. 1, 2016, s. 46-54.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Proteasome inhibitors and IMiDs can overcome some high-risk cytogenetics in multiple myeloma but not gain 1q21

AU - Nahi, Hareth

AU - Våtsveen, Thea Kristin

AU - Lund, Johan

AU - Heeg, Bart M S

AU - Preiss, Birgitte

AU - Alici, Evren

AU - Møller, Michael Boe

AU - Wader, Karin Fahl

AU - Møller, Hanne E H

AU - Grøseth, Lill Anny

AU - Østergaard, Brian

AU - Dai, Hong Yan

AU - Holmberg, Erik

AU - Gahrton, Gösta

AU - Waage, Anders

AU - Abildgaard, Niels

N1 - © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

U2 - 10.1111/ejh.12546

DO - 10.1111/ejh.12546

M3 - Journal article

VL - 96

SP - 46

EP - 54

JO - European Journal of Haematology

JF - European Journal of Haematology

SN - 0902-4441

IS - 1

ER -