Improving the multiple myeloma patient pathway: microsampling for remote monitoring of free light chains

Abstract

Multiple myeloma (MM) is categorised as a relapsing-remitting blood cancer with unpredictable relapse patterns. Due to an inevitable relapse, blood test monitoring is crucial and requires frequent visits to the phlebotomy clinics. The measurement of serum free light chains (FLC) can provide a rapid indication of MM disease progression and therapeutic response. Microsampling introduces a self-administered, capillary blood sampling technique that has potential to be a promising tool for remote MM monitoring. I begin by presenting the development of a dried blood spot (DBS) method for the quantitation of FLC. Here I show the associated analytical constraints inherent to DBS and the need to explore other microsampling devices for FLC analysis. Following this, I present a volumetric absorptive microsampling (VAMS) FLC method, utilising the Mitra device by Neoteryx, developed by adapting the Binding Site Freelite serum assay on the SPAPLUS. Method comparison studies between VAMS and conventional venepuncture were performed at the Royal Marsden Hospital MM clinic. VAMS and serum results showed a reasonable agreement for kappa (k) FLC (y = 9.43 +0.85x, R2 = 0.86) and lambda FLC (y = 2.66+1.10x, R2 = 0.91). Precision studies were within an acceptable range for k- and l-FLC (CV<15%). Limit of quantitation (LoQ) was determined to be 1mg/L for both methods. Linearity for the k- and l-FLC VAMS method was confirmed over a measuring range of 12-260 mg/L and 7-221mg/L, respectively. I also assessed MM patient perspectives on the current monitoring pathway and their satisfaction and preference for VAMS when compared to traditional methods for routine blood tests. Overall, 63% of patients preferred VAMS; 4% preferred phlebotomy; and 32% had no preference. Additionally, I evaluated a quantitative immunoprecipitation mass spectrometry (QIP-MS) system for the analysis of paraprotein via DBS, which brings together the power of microsampling and mass spectrometry, giving us a glimpse of how MM monitoring may look in the future. The work presented in this thesis highlights the benefits microsampling provides for the remote monitoring of MM, especially for patients who require frequent monitoring or who may be immunocompromised and vulnerable during travel or at a clinical setting.