# Dynamic Targetable Extracellular Vesicle Surface Proteins Monitor Depth of Response to CAR T Therapy

## TL;DR

This study introduces a new blood test using extracellular vesicles to track how well patients with multiple myeloma respond to CAR T therapy and predict relapse.

## Contribution

A novel EV surface protein assay is developed to dynamically monitor MM patient responses and survival in CAR T therapy.

## Key findings

- Four MM EV subpopulations significantly decreased in responding patients and increased in those with progression.
- CD319+ MM EVs predicted survival in MRD-negative patients and detected early relapse.
- The assay complements MRD testing by identifying antigen escape and monitoring deep response.

## Abstract

Extracellular vesicles (EVs) represent a promising liquid biopsy platform in multiple myeloma (MM). We developed an MM EV Surface Protein Assay to quantify and dynamically monitor four MM EV subpopulations defined by targetable MM surface proteins (BCMA, CD38, GPRC5D, and CD319) across 336 serial blood samples from 45 relapsed/refractory MM (RRMM) patients treated with anti-BCMA chimeric antigen receptor (CAR) T-cell therapy. All four MM EV subpopulations significantly decreased in 43 patients with initial response, while BCMA+, GPRC5D+, and CD319+ MM EVs increased in 19 patients with progression, and antigen escape was detected by BCMA+ MM EVs. MM EV subpopulations differentiated minimal residual disease (MRD) status and complemented MRD for detecting early relapse before clinical progression. Notably, CD319+ MM EVs were early predictors of progression-free and overall survival in MRD-negative patients. This assay enables noninvasive monitoring of deep response, progression, and antigen escape, and stratifies survival in MRD-negative patients with RRMM.