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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.coverage.spatialItalyen_US
dc.date.accessioned2019-03-04T14:38:36Z
dc.date.issued2019-02-07en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30733268en_US
dc.identifierhaematol.2018.202200en_US
dc.identifier.citationHaematologica, 2019en_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 the maximisation of response and use of maintenance therapy. We used whole exome sequencing to study the genetics of paired presentation and relapse samples from 56 newly diagnosed patients, following induction therapy, randomised 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 randomisation. Patients achieving a complete response had predominantly branching evolutionary patterns leading to relapse, characterised by a greater mutational burden, an altered mutational profile, bi-allelic inactivation of tumour 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. There were no significant differences between patients relapsing after maintenance lenalidomide vs observation. This study shows that the depth of response is a key determinant of the evolutionary patterns seen at relapse.en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectClonal evolutionen_US
dc.subjectImmunomodulatory therapyen_US
dc.subjectMaintenanceen_US
dc.subjectMultiple Myelomaen_US
dc.subjectRelapseen_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.startdate2019-02-07en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfHaematologicaen_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.publication-statusPublished onlineen_US
pubs.embargo.termsNot knownen_US
icr.researchteamTranslational Cancer Discoveryen_US
dc.contributor.icrauthorPawlyn, Charlotteen_US


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