Prediction of outcome in newly diagnosed myeloma: a meta-analysis of the molecular profiles of 1905 trial patients.
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Date
2018-01-01Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Subject
Humans
Multiple Myeloma
Neoplasm Recurrence, Local
Chromosome Aberrations
Chromosome Deletion
Translocation, Genetic
Prognosis
Disease-Free Survival
Transplantation, Autologous
Proportional Hazards Models
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
Clinical Trials, Phase III as Topic
Research team
Myeloma Biology and Therapeutics
Cancer Genomics
Myeloma Group
Language
eng
Date accepted
2017-05-25
License start date
2018-01
Citation
Leukemia, 2018, 32 (1), pp. 102 - 110
Publisher
NATURE PUBLISHING GROUP