dc.contributor.author | Kaiser, MF | |
dc.contributor.author | Hall, A | |
dc.contributor.author | Walker, K | |
dc.contributor.author | Sherborne, A | |
dc.contributor.author | De Tute, RM | |
dc.contributor.author | Newnham, N | |
dc.contributor.author | Roberts, S | |
dc.contributor.author | Ingleson, E | |
dc.contributor.author | Bowles, K | |
dc.contributor.author | Garg, M | |
dc.contributor.author | Lokare, A | |
dc.contributor.author | Messiou, C | |
dc.contributor.author | Houlston, RS | |
dc.contributor.author | Jackson, G | |
dc.contributor.author | Cook, G | |
dc.contributor.author | Pratt, G | |
dc.contributor.author | Owen, RG | |
dc.contributor.author | Drayson, MT | |
dc.contributor.author | Brown, SR | |
dc.contributor.author | Jenner, MW | |
dc.coverage.spatial | United States | |
dc.date.accessioned | 2023-08-01T14:33:54Z | |
dc.date.available | 2023-08-01T14:33:54Z | |
dc.date.issued | 2023-08-10 | |
dc.identifier.citation | Journal of Clinical Oncology, 2023, pp. JCO2202567 - | |
dc.identifier.issn | 0732-183X | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5912 | |
dc.identifier.eissn | 1527-7755 | |
dc.identifier.eissn | 1527-7755 | |
dc.identifier.doi | 10.1200/JCO.22.02567 | |
dc.description.abstract | PURPOSE: The multicenter OPTIMUM (MUKnine) phase II trial investigated daratumumab, low-dose cyclophosphamide, lenalidomide, bortezomib, and dexamethasone (Dara-CVRd) before and after autologous stem-cell transplant (ASCT) in newly diagnosed patients with molecularly defined ultra-high-risk (UHiR) multiple myeloma (NDMM) or plasma cell leukemia (PCL). To provide clinical context, progression-free survival (PFS) and overall survival (OS) were referenced to contemporaneous outcomes seen in patients with UHiR NDMM treated in the recent Myeloma XI (MyeXI) trial. METHODS: Transplant-eligible all-comers NDMM patients were profiled for UHiR disease, defined by presence of ≥2 genetic risk markers t(4;14)/t(14;16)/t(14;20), del(1p), gain(1q), and del(17p), and/or SKY92 gene expression risk signature. Patients with UHiR MM/PCL were offered treatment with Dara-CVRd induction, V-augmented ASCT, extended Dara-VR(d) consolidation, and Dara-R maintenance. UHiR patients treated in MyeXI with carfilzomib, lenalidomide, dexamethasone, and cyclophosphamide, or lenalidomide, dexamethasone, and cyclophosphamide, ASCT, and R maintenance or observation were identified by mirrored molecular screening. OPTIMUM PFS at 18 months (PFS18m) was compared against MyeXI using a Bayesian framework, and patients were followed up to the end of consolidation for PFS and OS. RESULTS: Of 412 screened NDMM OPTIMUM patients, 103 were identified as UHiR or PCL and subsequently treated on trial with Dara-CVRd; 117 MyeXI patients identified as UHiR formed the external comparator arm, with comparable clinical and molecular characteristics to OPTIMUM. Comparison of PFS18m per Bayesian framework resulted in a 99.5% chance of OPTIMUM being superior to MyeXI. At 30 months' follow-up, PFS was 77% for OPTIMUM versus 39.8% for MyeXI, and OS 83.5% versus 73.5%, respectively. Extended post-ASCT Dara-VRd consolidation therapy was highly deliverable, with limited toxicity. CONCLUSION: Our results suggest that Dara-CVRd induction and extended post-ASCT Dara-VRd consolidation markedly improve PFS for UHiR NDMM patients over conventional management, supporting further evaluation of this strategy. | |
dc.format | Print-Electronic | |
dc.format.extent | JCO2202567 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | LIPPINCOTT WILLIAMS & WILKINS | |
dc.relation.ispartof | Journal of Clinical Oncology | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.title | Daratumumab, Cyclophosphamide, Bortezomib, Lenalidomide, and Dexamethasone as Induction and Extended Consolidation Improves Outcome in Ultra-High-Risk Multiple Myeloma. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-05-02 | |
dc.date.updated | 2023-08-01T14:32:30Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1200/JCO.22.02567 | |
rioxxterms.licenseref.startdate | 2023-06-14 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37315268 | |
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/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Myeloma Molecular Therapy | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1200/jco.22.02567 | |
icr.researchteam | Myeloma Molecular Therapy | |
icr.researchteam | Cancer Genomics | |
dc.contributor.icrauthor | Kaiser, Martin | |
dc.contributor.icrauthor | Houlston, Richard | |
icr.provenance | Deposited by Mr Arek Surman (impersonating Prof Richard Houlston) on 2023-08-01. Deposit type is initial. No. of files: 1. Files: jco.22.02567.pdf | |