MUKnineOPTIMUM 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

Abstract

IntroductionMultiple myeloma (MM) is a plasma cell tumour with over 5800 new cases each year in the UK. 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.Methods and analysisThe Myeloma UK nine OPTIMUM trial (MUKnine) 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 (MUKnine a), 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 (MUKnine b) 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. MUKnine b 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.Ethics and disseminationEthics 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.Trial registration numberISRCTN16847817, May 2017; Pre-results.

Prognostic gene expression analysis in a retrospective, multinational cohort of 155 multiple myeloma patients treated outside clinical trials

“…By incorporating GEP‐based classifiers, additional high‐risk patients were detected that were not identified by other markers. These high‐risk patients had associated adverse outcomes and could potentially be referred to clinical trials focusing on this subpopulation 28 or could qualify for better monitoring and a more intense treatment.…”

Immune responses to COVID‐19 booster vaccinations in intensively anti‐CD38 antibody treated patients with ultra‐high‐risk multiple myeloma: results from the Myeloma UK (MUK) nine OPTIMUM trial

“…The study included samples from patients from the OPTIMUM trial 11 ; a sub‐cohort of up to 79% ( n = 85/107) recruited trial patients were included in the present analyses. Samples were also analysed from a non‐myeloma cohort: healthcare workers (HCW) who participated in the Immune response to SARS‐CoV‐2 infection (COCO) study 13 .…”

Perspectives on the Risk-Stratified Treatment of Multiple Myeloma

“…The preliminary results of ongoing risk-stratified studies further exploring the role of anti-CD38 mAbs are promising including the UAMS TT7 study, the German Multiple Myeloma group (GMMG; ref. 90 ) CONCEPT, and the UK MUK9B Optimum study ( 91, 92 ).…”