dc.contributor.author | Jones, JR | |
dc.contributor.author | Weinhold, N | |
dc.contributor.author | Ashby, C | |
dc.contributor.author | Walker, BA | |
dc.contributor.author | Wardell, C | |
dc.contributor.author | Pawlyn, C | |
dc.contributor.author | Rasche, L | |
dc.contributor.author | Melchor, L | |
dc.contributor.author | Cairns, DA | |
dc.contributor.author | Gregory, WM | |
dc.contributor.author | Johnson, D | |
dc.contributor.author | Begum, DB | |
dc.contributor.author | Ellis, S | |
dc.contributor.author | Sherborne, AL | |
dc.contributor.author | Cook, G | |
dc.contributor.author | Kaiser, MF | |
dc.contributor.author | Drayson, MT | |
dc.contributor.author | Owen, RG | |
dc.contributor.author | Jackson, GH | |
dc.contributor.author | Davies, FE | |
dc.contributor.author | Greaves, M | |
dc.contributor.author | Morgan, GJ | |
dc.contributor.author | NCRI Haemato-Oncology CSG, | |
dc.date.accessioned | 2019-03-04T14:38:36Z | |
dc.date.issued | 2019-06-30 | |
dc.identifier.citation | Haematologica, 2019, 104 (7), pp. 1440 - 1450 | |
dc.identifier.issn | 0390-6078 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3113 | |
dc.identifier.eissn | 1592-8721 | |
dc.identifier.doi | 10.3324/haematol.2018.202200 | |
dc.description.abstract | The 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.format | Print-Electronic | |
dc.format.extent | 1440 - 1450 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | FERRATA STORTI FOUNDATION | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | NCRI Haemato-Oncology CSG | |
dc.subject | Humans | |
dc.subject | Multiple Myeloma | |
dc.subject | Neoplasm Recurrence, Local | |
dc.subject | Thalidomide | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Treatment Outcome | |
dc.subject | Remission Induction | |
dc.subject | Follow-Up Studies | |
dc.subject | Gene Expression Profiling | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | Mutation | |
dc.subject | Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Maintenance Chemotherapy | |
dc.subject | Clonal Evolution | |
dc.subject | Biomarkers, Tumor | |
dc.subject | Whole Exome Sequencing | |
dc.subject | Lenalidomide | |
dc.title | Clonal 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.type | Journal Article | |
dcterms.dateAccepted | 2019-01-30 | |
rioxxterms.versionofrecord | 10.3324/haematol.2018.202200 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc/4.0 | |
rioxxterms.licenseref.startdate | 2019-07 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Haematologica | |
pubs.issue | 7 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 104 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Myeloma Biology and Therapeutics | |
icr.researchteam | Biology of Childhood Leukaemia | |
icr.researchteam | Myeloma Group | |
dc.contributor.icrauthor | Pawlyn, Charlotte | |
dc.contributor.icrauthor | Kaiser, Martin | |
dc.contributor.icrauthor | Greaves, Melvyn | |