High sensitivity mass spectrometry for multiple myeloma monitoring using microsampling: A patient-centered approach

Abstract Background: Microsampling presents a minimally invasive alternative to venipuncture, offering potential improvements in the routine monitoring of paraprotein levels in Multiple Myeloma (MM) patients. Mass spectrometry (MS), known for its high sensitivity in MM testing, complements bone marrow assessments and could be particularly beneficial when used with microsampling. This approach may facilitate frequent testing for patients with mobility restrictions. To ensure the acceptability of this, a focus group was formed to assess satisfaction and preferences regarding remote monitoring, and to contribute to the design and refinement of the study protocol for a larger study evaluating capillary blood use on the EXENT System for identifying and quantifying monoclonal immunoglobulins. Subsequently, the feasibility of monitoring MM patients with low sample volumes was first tested by diluting venipuncture serum samples and measuring immunoglobulins using turbidimetry and MS assays. Methods: A panel of individuals with lived experience of MM (n=19) and one caregiver (n=1) was recruited through Myeloma UK support group leaders. To ensure diverse representation, snowball sampling was used to reach underserved populations, leading to the inclusion of four seldom heard individuals. Two 2-hour focus group sessions were conducted, each involving 10–13 participants. The first session included an interactive demonstration of various microsampling devices currently available on the market. Discussions centered on general perceptions of microsampling, key considerations for selecting a suitable device, and overall acceptability from the patient and caregiver perspective. In the second session, the panel reviewed the trial design and provided feedback on patient-facing documents, including the patient information sheet, consent form, and study questionnaires. The sessions were recorded, transcribed, and analyzed using reflexive thematic analysis. As a proof of concept, serum immunoglobulins and paraproteins from three MM patients were measured by turbidimetry (Optilite) and MS (EXENT GAM assay), respectively. To simulate real microsampling volumes, serum samples from venipuncture were diluted 1:10 and 1:20 and measured with assays to detect low level immunoglobulins by turbidimetry. Interference with the EXENT GAM assay was assessed by running blank samples from Whatman 903 filter paper, Mitra, and Capitainer B50 devices. Results: Key themes identified from the moderated discussions included: (1) device usability and user experience, (2) sustainability, (3) analytical validity, and (4) safety. Panel members were generally supportive of microsampling. Participants provided meaningful suggestions to the study design based on their lived experience and emphasized the importance of making the patient-facing documents more concise and accessible. Additionally, respondents highlighted the need to strengthen recruitment strategies targeting underserved populations. For all three patients tested by MS, monoclonal protein quantification was concordant across both neat and low volume sample scenarios. No interference with MS was observed for any of the three microsampling devices evaluated. Conclusions: The consensus was that microsampling would be a welcome addition to the routine clinical care of MM. Involving the panel early in the study helped ensure the study design was better aligned with patient needs and preferences. The high sensitivity of MS, effective even on diluted serum samples, confirms its feasibility for use with the low volume samples obtained through microsampling. Offering an at-home blood collection method has the potential to significantly improve the patient pathway for monitoring MM. Importantly, for frail patients with limited mobility, microsampling combined with MS could enable highly sensitive remote monitoring, providing an alternative to venipuncture and even invasive bone marrow procedures for detecting low levels of disease.