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dc.contributor.authorJones, JRen_US
dc.contributor.authorWeinhold, Nen_US
dc.contributor.authorAshby, Cen_US
dc.contributor.authorWalker, BAen_US
dc.contributor.authorWardell, Cen_US
dc.contributor.authorPawlyn, Cen_US
dc.contributor.authorRasche, Len_US
dc.contributor.authorMelchor, Len_US
dc.contributor.authorCairns, DAen_US
dc.contributor.authorGregory, WMen_US
dc.contributor.authorJohnson, Den_US
dc.contributor.authorBegum, DBen_US
dc.contributor.authorEllis, Sen_US
dc.contributor.authorSherborne, ALen_US
dc.contributor.authorCook, Gen_US
dc.contributor.authorKaiser, MFen_US
dc.contributor.authorDrayson, MTen_US
dc.contributor.authorOwen, RGen_US
dc.contributor.authorJackson, GHen_US
dc.contributor.authorDavies, FEen_US
dc.contributor.authorGreaves, Men_US
dc.contributor.authorMorgan, GJen_US
dc.contributor.authorNCRI Haemato-Oncology CSGen_US
dc.coverage.spatialItalyen_US
dc.date.accessioned2019-03-04T14:38:36Z
dc.date.issued2019-07en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30733268en_US
dc.identifierhaematol.2018.202200en_US
dc.identifier.citationHaematologica, 2019, 104 (7), pp. 1440 - 1450en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3113
dc.identifier.eissn1592-8721en_US
dc.identifier.doi10.3324/haematol.2018.202200en_US
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.en_US
dc.format.extent1440 - 1450en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
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.en_US
dc.typeJournal Article
dcterms.dateAccepted2019-01-30en_US
rioxxterms.versionofrecord10.3324/haematol.2018.202200en_US
rioxxterms.licenseref.startdate2019-07en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfHaematologicaen_US
pubs.issue7en_US
pubs.notesNot knownen_US
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/Translational Cancer Discovery
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Myeloma Group
pubs.publication-statusPublisheden_US
pubs.volume104en_US
pubs.embargo.termsNot knownen_US
icr.researchteamTranslational Cancer Discoveryen_US
icr.researchteamMyeloma Groupen_US
dc.contributor.icrauthorPawlyn, Charlotteen_US
dc.contributor.icrauthorKaiser, Martinen_US


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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/