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The introduction of biological therapies has improved outcomes for the majority of patients with MM, but in approximately 20% of patients the tumour is characterised by genetic changes which confer a significantly poorer prognosis, generally termed high-risk (HR) MM. It is important to diagnose these genetic changes early and identify more effective first-line treatment options for these patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      The Myeloma UK\n                      <jats:italic>nine<\/jats:italic>\n                      OPTIMUM trial (MUK\n                      <jats:italic>nine<\/jats:italic>\n                      ) evaluates novel treatment strategies for patients with HRMM. Patients with suspected or newly diagnosed MM, fit for intensive therapy, are offered participation in a tumour genetic screening protocol (MUK\n                      <jats:italic>nine a<\/jats:italic>\n                      ), with primary endpoint proportion of patients with molecular screening performed within 8 weeks. Patients identified as molecularly HR are invited into the phase II, single-arm, multicentre trial (MUK\n                      <jats:italic>nine b<\/jats:italic>\n                      ) investigating an intensive treatment schedule comprising bortezomib, lenalidomide, daratumumab, low-dose cyclophosphamide and dexamethasone, with single high-dose melphalan and autologous stem cell transplantation (ASCT) followed by combination consolidation and maintenance therapy. MUK\n                      <jats:italic>nine b<\/jats:italic>\n                      primary endpoints are minimal residual disease (MRD) at day 100 post-ASCT and progression-free survival. Secondary endpoints include response, safety and quality of life. The trial uses a Bayesian decision rule to determine if this treatment strategy is sufficiently active for further study. Patients identified as not having HR disease receive standard treatment and are followed up in a cohort study. Exploratory studies include longitudinal whole-body diffusion-weighted MRI for imaging MRD testing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>Ethics approval London South East Research Ethics Committee (Ref: 17\/LO\/0022, 17\/LO\/0023). Results of studies will be submitted for publication in a peer-reviewed journal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"ISRCTN16847817\">ISRCTN16847817<\/jats:ext-link>\n                      , May 2017; Pre-results.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2020-046225","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T13:03:34Z","timestamp":1616591014000},"page":"e046225","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":26,"title":["MUK\n                    <i>nine<\/i>\n                    OPTIMUM protocol: a screening study to identify high-risk patients with multiple myeloma suitable for novel treatment approaches combined with a phase II study evaluating optimised combination of biological therapy in newly diagnosed high-risk multiple myeloma and plasma cell leukaemia"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7975-7537","authenticated-orcid":false,"given":"Sarah","family":"Brown","sequence":"first","affiliation":[{"name":"Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debbie","family":"Sherratt","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Hinsley","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"Flanagan","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sadie","family":"Roberts","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrina","family":"Walker","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Hall","sequence":"additional","affiliation":[{"name":"Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy","family":"Pratt","sequence":"additional","affiliation":[{"name":"Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Messiou","sequence":"additional","affiliation":[{"name":"Centre for Myeloma Research, Institute of Cancer Research, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Jenner","sequence":"additional","affiliation":[{"name":"Department of Haematology, Southampton General Hospital, Southampton, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Centre for Myeloma Research, Institute of Cancer Research, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2021,3,24]]},"reference":[{"key":"2025121222172341000_11.3.e046225.1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.291"},{"key":"2025121222172341000_11.3.e046225.2","unstructured":"Cancer Research UK . 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