A5072918409- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Cancer Treatment and Pharmacology
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Hematological disorders and diagnostics
- Ubiquitin and proteasome pathways
- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Malaria Research and Control
- Bone health and treatments
- Histone Deacetylase Inhibitors Research
- Cancer Mechanisms and Therapy
- Pharmacological Effects and Toxicity Studies
- Cancer Genomics and Diagnostics
- CAR-T cell therapy research
- Acute Myeloid Leukemia Research
- Cancer therapeutics and mechanisms
- Chronic Myeloid Leukemia Treatments
- SARS-CoV-2 and COVID-19 Research
- Hematopoietic Stem Cell Transplantation
- Platelet Disorders and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Renal Diseases and Glomerulopathies
Oxford University Hospitals NHS Trust
2016-2025
University of Oxford
2015-2025
Nuffield Orthopaedic Centre
2023-2025
John Radcliffe Hospital
2016-2025
Churchill Hospital
2014-2024
Jawaharlal Institute of Post Graduate Medical Education and Research
2024
University Medical Center Freiburg
2023
Oxford BioMedica (United Kingdom)
2014-2023
Royal Berkshire Hospital
2012-2023
National Health Service
2016-2023
Despite recent progress, multiple myeloma remains incurable. Mezigdomide is a novel cereblon E3 ubiquitin ligase modulator with potent antiproliferative and tumoricidal activity in preclinical models of myeloma, including those resistant to lenalidomide pomalidomide. In this phase 1–2 study, we administered oral mezigdomide combination dexamethasone patients relapsed refractory myeloma. The primary objectives 1 (dose-escalation cohort) were assess safety pharmacokinetics identify the dose...
Summary This guideline provides consensus opinion on the investigations required for people presenting with suspected monoclonal gammopathy of renal significance to both nephrology and haematology physicians. The discusses principles treating a patient MGRS recommendations supportive management haematological therapy. It details recommended on‐going monitoring specialty areas.
This final post hoc analysis evaluated patient-reported outcomes from the Phase 3 MAIA study of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus lenalidomide (Rd) after median 64.5-month follow-up in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM), including patient subgroups. Key scales EORTC QLQ-C30 (global health status [GHS], physical functioning, pain, fatigue) were assessed. Scores every months for 1 year, then 6 until disease progression. The...
Purpose Renal impairment (RI) limits treatment options in patients with relapsed/refractory multiple myeloma (RRMM). Here, we prospectively studied pomalidomide plus low-dose dexamethasone (LoDEX) RRMM and moderate or severe RI, including those receiving hemodialysis. Patients Methods MM-013, a noncomparative, European phase II trial, enrolled three patient cohorts: RI (cohort A; estimated glomerular filtration rate, 30 to < 45 mL/min/1.73 m2); B; that requires hemodialysis C). received 4...
The development of novel agents has transformed the treatment paradigm for multiple myeloma, with minimal residual disease (MRD) negativity now achievable across entire spectrum. Bone marrow-based technologies to assess MRD, including approaches using next-generation flow and sequencing, have provided real-time clinical tools sensitive detection monitoring MRD in patients myeloma. Complementary liquid biopsy-based assays are quickly progressing some, such as mass spectrometry methods, being...
Abstract Multiple myeloma is an incurable, bone marrow-dwelling malignancy that disrupts homeostasis causing skeletal damage and pain. Mechanisms underlying myeloma-induced destruction are poorly understood current therapies do not restore lost mass. Using transcriptomic profiling of isolated lining cell subtypes from a murine model, we find morphogenetic protein (BMP) signalling upregulated in stromal progenitor cells. BMP has previously been reported to be dysregulated disease. Inhibition...
8500 Background: CC-92480 is a novel cereblon E3 ligase modulator (CELMoD) agent designed for rapid, maximal degradation of Ikaros and Aiolos. In vitro, it has enhanced antiproliferative tumoricidal activity in MM cell lines, including those resistant to lenalidomide (LEN) pomalidomide (POM), with strong immune stimulatory activity. Methods: A phase 1, multicenter, dose-escalation study evaluated the maximum tolerated dose (MTD), recommended 2 dose, safety, tolerability, pharmacokinetics +...
We report the results of a Phase I/II dose escalation study to determine maximum tolerated (MTD) cyclophosphamide when combined with lenalidomide and dexamethasone in relapsed/refractory myeloma. Thirty-one patients were enrolled cohorts 3, at five levels 700 mg on days 1 8 28-d cycle. Patients received 25 1-21 20 orally 1-4 8-11. The MTD was 600 cyclophosphamide, 8. Grade 3/4 haematological complications occurred 26% patients, grade infection 3% (both cyclophosphamide), thromboembolic 6%...
To evaluate the effects of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus lenalidomide (Rd) on patient-reported outcomes (PROs) in phase III MAIA study.PROs were assessed European Organization for Research Treatment Cancer Quality Life Questionnaire Core 30-item EuroQol 5-dimensional descriptive system at baseline every 3 months during treatment. By mixed-effects model, changes from are presented as least squares means with 95% CIs.A total 737 transplant-ineligible (TIE) patients...
Summary Myeloma patients frequently respond poorly to bacterial and viral vaccination. A few studies have reported poor humoral immune responses in myeloma COVID‐19 Using a prospective study of the UK Rudy cohort, we assessed interferon gamma release assay (IGRA) cellular vaccination post second vaccine administration. We report data from 214 adults with ( n = 204) or smouldering 10) who provided blood samples at least three weeks after dose. Positive Anti‐spike antibody levels (> 50...
Abstract Multiple myeloma (MM) is a plasma cell malignancy characterised by aberrant production of immunoglobulins requiring survival mechanisms to adapt proteotoxic stress. We here show that glutamyl-prolyl-tRNA synthetase (GluProRS) inhibition constitutes novel therapeutic target. Genomic data suggest GluProRS promotes disease progression and associated with poor prognosis, while downregulation in MM cells triggers apoptosis. developed NCP26, ATP-competitive ProRS inhibitor demonstrates...
Multiple myeloma is a bone marrow-based plasma cell tumour that develops from asymptomatic pre-cursor conditions smouldering and monoclonal gammopathy of uncertain significance all are characterised by the presence protein in blood. Diagnosis distinction between these based on blood tests, marrow biopsy cross sectional imaging. There various risk stratification models group patients with into groups progression to symptomatic disease. Management mainly observational for although clinical...