Prediction of outcome in newly diagnosed myeloma: a meta-analysis of the molecular profiles of 1905 trial patients.
Loading...
Embargo End Date
Authors
Shah, V
Sherborne, AL
Walker, BA
Johnson, DC
Boyle, EM
Ellis, S
Begum, DB
Proszek, PZ
Jones, JR
Pawlyn, C
Savola, S
Jenner, MW
Drayson, MT
Owen, RG
Houlston, RS
Cairns, DA
Gregory, WM
Cook, G
Davies, FE
Jackson, GH
Morgan, GJ
Kaiser, MF
Sherborne, AL
Walker, BA
Johnson, DC
Boyle, EM
Ellis, S
Begum, DB
Proszek, PZ
Jones, JR
Pawlyn, C
Savola, S
Jenner, MW
Drayson, MT
Owen, RG
Houlston, RS
Cairns, DA
Gregory, WM
Cook, G
Davies, FE
Jackson, GH
Morgan, GJ
Kaiser, MF
Document Type
Journal Article
Date
2018-01-01
Date Accepted
2017-05-25
Abstract
Robust establishment of survival in multiple myeloma (MM) and its relationship to recurrent genetic aberrations is required as outcomes are variable despite apparent similar staging. We assayed copy number alterations (CNA) and translocations in 1036 patients from the NCRI Myeloma XI trial and linked these to overall survival (OS) and progression-free survival. Through a meta-anlysis of these data with data from MRC Myeloma IX trial, totalling 1905 newly diagnosed MM patients (NDMM), we confirm the association of t(4;14), t(14;16), t(14;20), del(17p) and gain(1q21) with poor prognosis with hazard ratios (HRs) for OS of 1.60 (P=4.77 × 10-7), 1.74 (P=0.0005), 1.90 (P=0.0089), 2.10 (P=8.86 × 10-14) and 1.68 (P=2.18 × 10-14), respectively. Patients with 'double-hit' defined by co-occurrence of at least two adverse lesions have an especially poor prognosis with HRs for OS of 2.67 (P=8.13 × 10-27) for all patients and 3.19 (P=1.23 × 10-18) for intensively treated patients. Using comprehensive CNA and translocation profiling in Myeloma XI we also demonstrate a strong association between t(4;14) and BIRC2/BIRC3 deletion (P=8.7 × 10-15), including homozygous deletion. Finally, we define distinct sub-groups of hyperdiploid MM, with either gain(1q21) and CCND2 overexpression (P<0.0001) or gain(11q25) and CCND1 overexpression (P<0.0001). Profiling multiple genetic lesions can identify MM patients likely to relapse early allowing stratification of treatment.
Citation
Leukemia, 2018, 32 (1), pp. 102 - 110
Source Title
Publisher
NATURE PUBLISHING GROUP
ISSN
0887-6924
eISSN
1476-5551
Research Team
Myeloma Biology and Therapeutics
Cancer Genomics
Myeloma Group
Cancer Genomics
Myeloma Group