Identification of Extracellular Vesicle Signatures of Daratumumab Treated Multiple Myeloma

Daratumumab (DARA) is a human monoclonal antibody for the treatment of multiple myeloma (MM), an incurable hematologic malignancy characterised by the accumulation of malignant plasma cells, located in the bone marrow (BM). We previously reported that peripheral blood plasma (PB) extracellular vesicles (EVs), isolated from 57 MM patients treated with DARA contain elevated CD55, CD59 and CD147 relative to healthy PB EVs, and elevated PDL1 was associated with patient response to DARA. The aim of this study was to identify additional proteins altered in these patients in order to generate predictive MM EV protein signatures. Flow cytometry analysis revealed that CD31, CD36 and CD44 were significantly elevated in MM PB EVs relative to healthy PB EVs, while CD8 and LAT1 were significantly decreased. CD38, LAT1 and PDL1 were significantly higher in PB EVs of patients with a long-term response to DARA. Multivariate ROC curves revealed a diagnostic signature (MM panel) with a sensitivity 86.4% and specificity 91.6%, and a predictive signature (Response panel) with a sensitivity 80% and specificity 91.2%. In conclusion we identified two EV signatures that may have potential as a non-invasive liquid biopsy to complement or replace invasive BM sampling for monitoring patient response to DARA.