Improving the Monitoring of Multiple Myeloma Patients Using Blood Based Markers of Disease
Multiple myeloma (MM) is a haematological malignancy characterised by the proliferation of clonal plasma cells in the bone marrow, usually leading to the secretion of a monoclonal immunoglobulin termed the M-protein. Multiple myeloma is a complex disease, and despite great advances in both detection and treatment of the disease, there remains a vast amount of interest in improving patient outcomes. In the era of novel agents and clinical trials, patients with MM are living longer and there is a requirement for frequent monitoring to assess treatment response and signs of relapse. Despite these improvements in treatment, even those patients achieving deep responses are still relapsing due to the presence of very low levels of residual disease, termed minimal residual disease (MRD). Increasingly sensitive techniques are needed to detect this MRD and, as MM is a bone marrow based disease, the majority of techniques focus on bone marrow based assays. However, as bone marrow sampling is invasive, painful and unpleasant for patients it is important to investigate whether blood-based assays could be equally or more informative of disease status. This project therefore aimed to obtain evidence as to whether blood-based assays can act as a safe and effective marker for disease in the bone marrow of treated multiple myeloma patients. Firstly, a bone marrow flow cytometry assay was validated to act as the gold standard technique. Next, three blood-based assays were investigated: circulating tumour plasma cell measurement, heavy/light chain measurement and mass spectrometry evaluation. This study shows the significance of blood-based assays at different disease stages in both transplant and nontransplant treated patients. These results lead to the suggestion of a testing algorithm focused on the addition of heavy/light chain measurement which can be pre-emptively used to influence decisions regarding bone marrow analysis and treatment, ultimately improving the patient experience.
Networked Digital Library of Theses and Dissertations