Faculty Collaboration Database

Prediction of outcome in newly diagnosed myeloma: a meta-analysis of the molecular profiles of 1905 trial patients. Leukemia 2018 Jan;32(1):102-110

Date

06/07/2017

Pubmed ID

28584253

Pubmed Central ID

PMC5590713

DOI

10.1038/leu.2017.179

Scopus ID

2-s2.0-85044620380 (requires institutional sign-in at Scopus site)   165 Citations

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.

Author List

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

Author

Test W. User test user title in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Chromosome Aberrations
Chromosome Deletion
Clinical Trials, Phase III as Topic
Disease-Free Survival
Female
Humans
Male
Middle Aged
Multiple Myeloma
Neoplasm Recurrence, Local
Prognosis
Proportional Hazards Models
Translocation, Genetic
Transplantation, Autologous