# Identification of Extracellular Vesicle Signatures of Daratumumab Treated Multiple Myeloma

## TL;DR

This study identifies extracellular vesicle protein signatures in blood that could help monitor multiple myeloma patients treated with Daratumumab, potentially replacing invasive bone marrow tests.

## Contribution

The study identifies new EV protein signatures for diagnosing and predicting response to Daratumumab in multiple myeloma.

## Key findings

- Five EV proteins were significantly different in MM patients compared to healthy controls.
- Three EV proteins were associated with long-term response to Daratumumab treatment.
- EV signatures showed high sensitivity and specificity for diagnosis and treatment prediction.

## Abstract

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.

Multiple myeloma peripheral blood extracellular vesicles (EVs) are a source of non‐invasive biomarkers with potential for routine monitoring and to complement or replace invasive bone marrow biopsy. In this study, five proteins were significantly different from healthy controls and three associated with long‐term response on Daratumumab which may have diagnostic/prognostic value.