Prognostic significance of cytogenetic heterogeneity in patients with newly diagnosed multiple myeloma
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Prognostic significance of cytogenetic heterogeneity in patients with newly diagnosed multiple myeloma. / Merz, Maximilian; Jauch, Anna; Hielscher, Thomas; Bochtler, Tilmann; Schönland, Stefan Olaf; Seckinger, Anja; Hose, Dirk; Bertsch, Uta; Neben, Kai; Raab, Marc Steffen; Hillengass, Jens; Salwender, Hans; Blau, Igor Wolfgang; Lindemann, Hans-Walter; Schmidt-Wolf, Ingo G H; Scheid, Christof; Haenel, Mathias; Weisel, Katja C; Goldschmidt, Hartmut.
in: BLOOD ADV, Jahrgang 2, Nr. 1, 09.01.2018, S. 1-9.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Prognostic significance of cytogenetic heterogeneity in patients with newly diagnosed multiple myeloma
AU - Merz, Maximilian
AU - Jauch, Anna
AU - Hielscher, Thomas
AU - Bochtler, Tilmann
AU - Schönland, Stefan Olaf
AU - Seckinger, Anja
AU - Hose, Dirk
AU - Bertsch, Uta
AU - Neben, Kai
AU - Raab, Marc Steffen
AU - Hillengass, Jens
AU - Salwender, Hans
AU - Blau, Igor Wolfgang
AU - Lindemann, Hans-Walter
AU - Schmidt-Wolf, Ingo G H
AU - Scheid, Christof
AU - Haenel, Mathias
AU - Weisel, Katja C
AU - Goldschmidt, Hartmut
PY - 2018/1/9
Y1 - 2018/1/9
N2 - 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.
AB - 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.
KW - Adolescent
KW - Adult
KW - Antineoplastic Combined Chemotherapy Protocols
KW - Bortezomib
KW - Chromosome Aberrations
KW - Humans
KW - In Situ Hybridization, Fluorescence
KW - Middle Aged
KW - Multiple Myeloma
KW - Netherlands
KW - Prognosis
KW - Transplantation, Autologous
KW - Young Adult
KW - Clinical Trial, Phase III
KW - Journal Article
KW - Randomized Controlled Trial
KW - Research Support, Non-U.S. Gov't
U2 - 10.1182/bloodadvances.2017013334
DO - 10.1182/bloodadvances.2017013334
M3 - SCORING: Journal article
C2 - 29344579
VL - 2
SP - 1
EP - 9
JO - BLOOD ADV
JF - BLOOD ADV
SN - 2473-9529
IS - 1
ER -