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dc.contributor.authorJones, JR
dc.contributor.authorWeinhold, N
dc.contributor.authorAshby, C
dc.contributor.authorWalker, BA
dc.contributor.authorWardell, C
dc.contributor.authorPawlyn, C
dc.contributor.authorRasche, L
dc.contributor.authorMelchor, L
dc.contributor.authorCairns, DA
dc.contributor.authorGregory, WM
dc.contributor.authorJohnson, D
dc.contributor.authorBegum, DB
dc.contributor.authorEllis, S
dc.contributor.authorSherborne, AL
dc.contributor.authorCook, G
dc.contributor.authorKaiser, MF
dc.contributor.authorDrayson, MT
dc.contributor.authorOwen, RG
dc.contributor.authorJackson, GH
dc.contributor.authorDavies, FE
dc.contributor.authorGreaves, M
dc.contributor.authorMorgan, GJ
dc.contributor.authorNCRI Haemato-Oncology CSG
dc.date.accessioned2019-03-04T14:38:36Z
dc.date.issued2019-07
dc.identifier.citationHaematologica, 2019, 104 (7), pp. 1440 - 1450
dc.identifier.issn0390-6078
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3113
dc.identifier.eissn1592-8721
dc.identifier.doi10.3324/haematol.2018.202200
dc.description.abstractThe emergence of treatment resistant sub-clones is a key feature of relapse in multiple myeloma. Therapeutic attempts to extend remission and prevent relapse include maximizing response and the use of maintenance therapy. We used whole exome sequencing to study the genetics of paired samples taken at presentation and at relapse from 56 newly diagnosed patients, following induction therapy, randomized to receive either lenalidomide maintenance or observation as part of the Myeloma XI trial. Patients included were considered high risk, relapsing within 30 months of maintenance randomization. Patients achieving a complete response had predominantly branching evolutionary patterns leading to relapse, characterized by a greater mutational burden, an altered mutational profile, bi-allelic inactivation of tumor suppressor genes, and acquired structural aberrations. Conversely, in patients achieving a partial response, the evolutionary features were predominantly stable with a similar mutational and structural profile seen at both time points. There were no significant differences between patients relapsing after lenalidomide maintenance versus observation. This study shows that the depth of response is a key determinant of the evolutionary patterns seen at relapse. This trial is registered at clinicaltrials.gov identifier: 01554852.
dc.formatPrint-Electronic
dc.format.extent1440 - 1450
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectNCRI Haemato-Oncology CSG
dc.subjectHumans
dc.subjectMultiple Myeloma
dc.subjectNeoplasm Recurrence, Local
dc.subjectThalidomide
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectTreatment Outcome
dc.subjectRemission Induction
dc.subjectFollow-Up Studies
dc.subjectGene Expression Profiling
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectMutation
dc.subjectAged
dc.subjectFemale
dc.subjectMale
dc.subjectMaintenance Chemotherapy
dc.subjectClonal Evolution
dc.subjectBiomarkers, Tumor
dc.subjectWhole Exome Sequencing
dc.subjectLenalidomide
dc.titleClonal evolution in myeloma: the impact of maintenance lenalidomide and depth of response on the genetics and sub-clonal structure of relapsed disease in uniformly treated newly diagnosed patients.
dc.typeJournal Article
dcterms.dateAccepted2019-01-30
rioxxterms.versionofrecord10.3324/haematol.2018.202200
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc/4.0
rioxxterms.licenseref.startdate2019-07
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfHaematologica
pubs.issue7
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Myeloma Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Biology of Childhood Leukaemia
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Myeloma Group
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Myeloma Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Biology of Childhood Leukaemia
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Myeloma Group
pubs.publication-statusPublished
pubs.volume104
pubs.embargo.termsNot known
icr.researchteamMyeloma Biology and Therapeuticsen_US
icr.researchteamBiology of Childhood Leukaemiaen_US
icr.researchteamMyeloma Groupen_US
dc.contributor.icrauthorPawlyn, Charlotteen
dc.contributor.icrauthorJones, Johnen
dc.contributor.icrauthorKaiser, Martinen
dc.contributor.icrauthorGreaves, Melvynen


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