Journal Article

DKFZ-2018-01908

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Prognostic significance of cytogenetic heterogeneity in patients with newly diagnosed multiple myeloma.

Merz, M. ; Jauch, A. ; Hielscher, T.DKFZ* ; Bochtler, T. ; Schönland, S. O. ; Seckinger, A. ; Hose, D. ; Bertsch, U. ; Neben, K. ; Raab, M. S.DKFZ* ; Hillengass, J. ; Salwender, H. ; Blau, I. W. ; Lindemann, H.-W. ; Schmidt-Wolf, I. G. H. ; Scheid, C. ; Haenel, M. ; Weisel, K. C. ; Goldschmidt, H.

2018
American Society of Hematology Washington, DC

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Please use a persistent id in citations: doi:10.1182/bloodadvances.2017013334

Abstract: We investigated subclonal cytogenetic aberrations (CA) detected by interphase fluorescence in situ hybridization (iFISH) in patients with newly diagnosed multiple myeloma (MM) enrolled in the Haemato Oncology Foundation for Adults in the Netherlands (HOVON)-65/German-Speaking MM Group (GMMG)-HD4 phase 3 trial. Patients were either treated with 3 cycles of vincristine, Adriamycin, and dexamethasone or bortezomib, Adriamycin, and dexamethasone and then thalidomide or bortezomib maintenance after tandem autologous transplantation. Subclones were defined either by presence of different copy numbers of the same chromosome loci and/or CA present in at least 30% less and maximally 2/3 of cells compared with the main clone CA. Patients with subclones harbored more frequently high risk (31.0%) or hyperdiploid main clone aberrations (24.8%) than patients with t(11;14) in the main clone (10.1%). Gains and deletions of c-MYC were the only CA that occurred more frequently as subclone (8.1%/20.5%) than main clone (6.2%/3.9%, respectively). Treatment with bortezomib completely overcame the negative prognosis of high-risk CA in patients without subclones, but not in patients with additional subclonal CA. High-risk patients treated without bortezomib showed dismal outcome whether subclones were present or not. Cytogenetic heterogeneity defined by subclonal CA is of major prognostic significance in newly diagnosed MM patients treated with bortezomib within the HOVON-65/GMMG-HD4 trial.

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Contributing Institute(s):

1. Biostatistik (C060)
2. Experimentelle Therapien hämatologischer Neoplasien (G170)

Research Program(s):

1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2018

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Database coverage:
; Clarivate Analytics Master Journal List ; Emerging Sources Citation Index ; PubMed Central ; Web of Science Core Collection

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