High-sensitivity free light chain detection for minimal residual disease analysis in multiple myeloma

Jeewa, Bilal (2024). High-sensitivity free light chain detection for minimal residual disease analysis in multiple myeloma. University of Birmingham. M.Sc.

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Abstract

Purpose: To overcome the various limitations of bone marrow-based minimal residual disease (MRD) measurement in patients with multiple myeloma (MM), the clinical Immunology service (CIS) at the University of Birmingham has developed a non-invasive, serum-based technique named hsFLC, which is capable of MRD detection via high-sensitive measurement of serum free light chains (FLCs). We compared MRD results from hsFLC analysis with those produced using multi-parameter flow cytometry (MFC). We also assessed the potential application of hsFLC for the diagnosis and monitoring of non-secretory (NS) and low-level FLC secretory MM patients.

Methods: The hsFLC assay combines isoelectric focussing with immunoblotting, and uses highly- specific mouse monoclonal antibodies targeted to FLCs. A total of 110 MM patient samples from the national Myeloma X & XI trials who had all undergone autologous stem cell transplants, were retrospectively analysed by hsFLC for the presence of MRD. From the selected patients, 54 had m-proteins with involved Kappa FLCs and 56 had involved Lambda FLCs at diagnosis. The original MRD results by MFC were available for 80 of these patients. A total of 29 MM patients clinically classified as NS from the national myeloma IX and XI clinical trials were also analysed by hsFLC for the presence of monoclonal FLCs. A small analysis of light-chain only MM (LCMM) and oligo-secretory MM (OSMM) patients was also conducted using hsFLC.

Results: Monoclonal FLCs were detected by hsFLC in all of the primary diagnostic samples tested, including the NSMM, LCMM and OSMM patients. MRD was detected in around double the number of post-transplant patients as those that were MRD-positive by MFC. Retrospective analysis of disease relapsed patients by hsFLC, demonstrated monoclonal FLCs several months before conventional methods detected any disease.

Conclusions: The hsFLC assay is a highly-sensitive and non-invasive alternative to bone marrow-based techniques for the systemic measurement of disease in almost all MM patients.

Type of Work:

Thesis (Masters by Research > M.Sc.)

Award Type:

Masters by Research > M.Sc.

Supervisor(s):