Prognostic impact of 1q21 amplification for newly diagnosed and
relapsed/refractory multiple myeloma patients enrolled in Brno,
Czech Republic.

D 2007

Prognostic impact of 1q21 amplification for newly diagnosed and relapsed/refractory multiple myeloma patients enrolled in Brno, Czech Republic.

NĚMEC, Pavel, Petr KUGLÍK, Hana FILKOVÁ, Henrieta GREŠLIKOVÁ, Romana ZAORALOVÁ et. al.

Basic information

Original name

Prognostic impact of 1q21 amplification for newly diagnosed and relapsed/refractory multiple myeloma patients enrolled in Brno, Czech Republic.

Name in Czech

Prognostický vliv amplifikace 1q21 u pacientů s mnohočetným myelomem nově diagnostikovaných a pacientů v relapsu léčených ve Fakultní nemocnici Brno

Authors

NĚMEC, Pavel, Petr KUGLÍK, Hana FILKOVÁ, Henrieta GREŠLIKOVÁ, Romana ZAORALOVÁ, Jana SMEJKALOVÁ, Alexandra OLTOVÁ and Roman HÁJEK

Edition

Brno, Czech Republic, From cell sorting to plasma cell identification and detection chromosomal aberrations in multiple myeloma. Abstract and Application Manual, p. 9-11, 3 pp. 2007

Publisher

Masaryk University

Other information

Language

English

Type of outcome

Stať ve sborníku

Field of Study

Genetics and molecular biology

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

Organization unit

Faculty of Medicine

ISBN

978-80-210-4417-3

Keywords in English

multiple myeloma; 1q21 amplification; fluorescence in situ hybridisation; DNA probe; Velcade; Thalidomide

Abstract

ORIG CZ

V originále

Introduction Fluorescence in situ hybridisation (FISH) has become a powerful technique for prognostic assessment in multiple myeloma (MM). Amplification of chromosome band 1q21 as well as increased expression of CKS1B gene in this area is a frequently mentioned prognostic factor for patients with multiple myeloma. A total of 88 patients enrolled in Faculty Hospital Brno, Czech Republic have been analyzed by FISH for presence of 1q21 amplification (Amp(1q21)). Impact of Amp(1q21) in clinical parameters (treatment responses and selected "end-point" intervals) in 39 patients with newly diagnosed MM enrolled in CMG2002 trial (4 cycles of VAD followed by high-dose therapy - melphalan 200mg/m2 supported by autologous stem cell transplantation (ASCT)) were statistically analysed. In a similar way a subset of 49 relapsed patients with at least 1 prior treatment line were analysed separatelly in groups divided according to treatment based regimen (Thalidomide or Velcade). See Table 1 for patients baseline characteristics. Results valid for newly diagnosed patients: Amp(1q21) was found in 41% (16/39) patients. Clinical parameters valid for patients with Amp(1q21) versus patients lacking Amp(1q21) were as follows: overall response rate (ORR) achieved 87.5% (14/16) vs. 91.3% (21/23) patients (p=0.404); overall survival (OS) median was 22.4 months vs. not yet reached (NR) (p=0.022); time to progression (TTP) median was 16.1 months vs. NR (p=0.010); progression-free survival (PFS) median was 15.6 vs. 25.2 months (p=0.023); and duration of response (DOR) median was 15.9 months vs. NR (p=0.048). Results valid for relapsed patients: Amp(1q21) was found in 61.2% (30/49) patients. Thalidomide based regimen group Amp(1q21) was found in 40.7% (11/27) patients. Clinical parameters valid for patients with Amp(1q21) versus patients lacking Amp(1q21) were as follows: ORR achieved 83.3% (5/6) vs. 80% (8/10), (p=0.868); OS median was 6.6 months vs. NR (p=0.072); TTP median was 12.1 vs. 8.2 months (p=0.269); and PFS median was 11.7 vs. 8.2 months (p=0.484). Velcade based regimen group Amp(1q21) was found in 86.4% (19/22) patients. Clinical parameters valid for patients with Amp(1q21) versus patients lacking Amp(1q21) were as follows: ORR achieved 50% (7/14) vs. 66.7% (2/3), (p=0.316); OS median was NR vs. NR (p=0.937); TTP median was 8 months vs. NR (p=0.442); and PFS median was 6.5 months vs. NR (p=0.637). Conclusion In conclusion, patients with Amp(1q21) treated by ASCT have significant shorter PFS median (15.6 months) when compared with patients lacking Amp(1q21) with PFS median 25.2 months (p=0.023). There were found statistical significant difference in all named "end- point" intervals (OS, TTP, PFS and DOR) between patients with/without Amp(1q21) but not in ORR. This findings is in accordance with previously published work (Chang et al., 2006). Relapsed patients with Amp(1q21) treated by thalidomide based regimen show a trend towards the worst prognosis based on overall survival when compared with patients lacking Amp(1q21) suggesting that thalidomide probably cannot overcome negative prognostic impact of this aberration. None significant differences between clinical parameters of patients with/without Amp(1q21) treated with Velcade based regimen were observed. However these findings has to be confirmed on a larger cohort of patients. These data are valid for July 2007. Supported by Monoclonal Gammopathy and Multiple Myeloma Basic Research Centre (LC 06027), Masaryk University, Brno, Czech Republic, and by grant of Ministry of Education (MSM0021622415), Czech Republic, and grant of Ministry of Medicine (IGA NR9317-3), Czech Republic.

In Czech

Práce pojednává o významu amplifikace 1q21 u pacientů s mnohočetným myelomem léčených Velcade, thalidomidem a konvenční terapií. Výsledky jsou hodnoceny u pacientů léčených ve Fakultní nemocnici Brno.

Links

LC06027, research and development project

Name: Univerzitní výzkumné centrum - Česká myelomová skupina (Acronym: LC MGUS)

Investor: Ministry of Education, Youth and Sports of the CR, University Research Centre - Czech Myeloma Group

MSM0021622415, plan (intention)

Name: Molekulární podstata buněčných a tkáňových regulací

Investor: Ministry of Education, Youth and Sports of the CR, Molecular basis of cell and tissue regulations

NR9317, research and development project

Name: Prognostický význam klonálních chromosomových aberací při použití nových léčebných metod u mnohočetného myelomu

Citovat

NĚMEC, Pavel, Petr KUGLÍK, Hana FILKOVÁ, Henrieta GREŠLIKOVÁ, Romana ZAORALOVÁ, Jana SMEJKALOVÁ, Alexandra OLTOVÁ and Roman HÁJEK. Prognostic impact of 1q21 amplification for newly diagnosed and relapsed/refractory multiple myeloma patients enrolled in Brno, Czech Republic. In From cell sorting to plasma cell identification and detection chromosomal aberrations in multiple myeloma. Abstract and Application Manual. Brno, Czech Republic: Masaryk University, 2007, p. 9-11. ISBN 978-80-210-4417-3.

@inproceedings{726970,
   author = {Němec, Pavel and Kuglík, Petr and Filková, Hana and Grešliková, Henrieta and Zaoralová, Romana and Smejkalová, Jana and Oltová, Alexandra and Hájek, Roman},
   address = {Brno, Czech Republic},
   booktitle = {From cell sorting to plasma cell identification and detection chromosomal aberrations in multiple myeloma. Abstract and Application Manual},
   keywords = {multiple myeloma; 1q21 amplification; fluorescence in situ hybridisation; DNA probe; Velcade; Thalidomide},
   language = {eng},
   location = {Brno, Czech Republic},
   isbn = {978-80-210-4417-3},
   pages = {9-11},
   publisher = {Masaryk University},
   title = {Prognostic impact of 1q21 amplification for newly diagnosed and relapsed/refractory multiple myeloma patients enrolled in Brno, Czech Republic.},
   year = {2007}
}

TY  - JOUR
ID  - 726970
AU  - Němec, Pavel - Kuglík, Petr - Filková, Hana - Grešliková, Henrieta - Zaoralová, Romana - Smejkalová, Jana - Oltová, Alexandra - Hájek, Roman
PY  - 2007
TI  - Prognostic impact of 1q21 amplification for newly diagnosed and relapsed/refractory multiple myeloma patients enrolled in Brno, Czech Republic.
PB  - Masaryk University
CY  - Brno, Czech Republic
SN  - 9788021044173
KW  - multiple myeloma
KW  - 1q21 amplification
KW  - fluorescence in situ hybridisation
KW  - DNA probe
KW  - Velcade
KW  - Thalidomide
N2  - Introduction Fluorescence in situ hybridisation (FISH) has become a powerful technique for prognostic assessment in multiple myeloma (MM). Amplification of chromosome band 1q21 as well as increased expression of CKS1B gene in this area is a frequently mentioned prognostic factor for patients with multiple myeloma. A total of 88 patients enrolled in Faculty Hospital Brno, Czech Republic have been analyzed by FISH for presence of 1q21 amplification (Amp(1q21)). Impact of Amp(1q21) in clinical parameters (treatment responses and selected "end-point" intervals) in 39 patients with newly diagnosed MM enrolled in CMG2002 trial (4 cycles of VAD followed by high-dose therapy - melphalan 200mg/m2 supported by autologous stem cell transplantation (ASCT)) were statistically analysed. In a similar way a subset of 49 relapsed patients with at least 1 prior treatment line were analysed separatelly in groups divided according to treatment based regimen (Thalidomide or Velcade). See Table 1 for patients baseline characteristics. Results valid for newly diagnosed patients: Amp(1q21) was found in 41% (16/39) patients. Clinical parameters valid for patients with Amp(1q21) versus patients lacking Amp(1q21) were as follows: overall response rate (ORR) achieved 87.5% (14/16) vs. 91.3% (21/23) patients (p=0.404); overall survival (OS) median was 22.4 months vs. not yet reached (NR) (p=0.022); time to progression (TTP) median was 16.1 months vs. NR (p=0.010); progression-free survival (PFS) median was 15.6 vs. 25.2 months (p=0.023); and duration of response (DOR) median was 15.9 months vs. NR (p=0.048). Results valid for relapsed patients: Amp(1q21) was found in 61.2% (30/49) patients. Thalidomide based regimen group Amp(1q21) was found in 40.7% (11/27) patients. Clinical parameters valid for patients with Amp(1q21) versus patients lacking Amp(1q21) were as follows: ORR achieved 83.3% (5/6) vs. 80% (8/10), (p=0.868); OS median was 6.6 months vs. NR (p=0.072); TTP median was 12.1 vs. 8.2 months (p=0.269); and PFS median was 11.7 vs. 8.2 months (p=0.484). Velcade based regimen group Amp(1q21) was found in 86.4% (19/22) patients. Clinical parameters valid for patients with Amp(1q21) versus patients lacking Amp(1q21) were as follows: ORR achieved 50% (7/14) vs. 66.7% (2/3), (p=0.316); OS median was NR vs. NR (p=0.937); TTP median was 8 months vs. NR (p=0.442); and PFS median was 6.5 months vs. NR (p=0.637). Conclusion In conclusion, patients with Amp(1q21) treated by ASCT have significant shorter PFS median (15.6 months) when compared with patients lacking Amp(1q21) with PFS median 25.2 months (p=0.023). There were found statistical significant difference in all named "end- point" intervals (OS, TTP, PFS and DOR) between patients with/without Amp(1q21) but not in ORR. This findings is in accordance with previously published work (Chang et al., 2006). Relapsed patients with Amp(1q21) treated by thalidomide based regimen show a trend towards the worst prognosis based on overall survival when compared with patients lacking Amp(1q21) suggesting that thalidomide probably cannot overcome negative prognostic impact of this aberration. None significant differences between clinical parameters of patients with/without Amp(1q21) treated with Velcade based regimen were observed. However these findings has to be confirmed on a larger cohort of patients. These data are valid for July 2007. Supported by Monoclonal Gammopathy and Multiple Myeloma Basic Research Centre (LC 06027), Masaryk University, Brno, Czech Republic, and by grant of Ministry of Education (MSM0021622415), Czech Republic, and grant of Ministry of Medicine (IGA NR9317-3), Czech Republic.
ER  -

NĚMEC, Pavel, Petr KUGLÍK, Hana FILKOVÁ, Henrieta GREŠLIKOVÁ, Romana ZAORALOVÁ, Jana SMEJKALOVÁ, Alexandra OLTOVÁ and Roman HÁJEK. Prognostic impact of 1q21 amplification for newly diagnosed and relapsed/refractory multiple myeloma patients enrolled in Brno, Czech Republic. In \textit{From cell sorting to plasma cell identification and detection chromosomal aberrations in multiple myeloma. Abstract and Application Manual}. Brno, Czech Republic: Masaryk University, 2007, p.~9-11. ISBN~978-80-210-4417-3.

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